Effect of GC and stress on activities of various types of deiodinases in rat tissues (↑ – stimulatory effect; ↓– inhibitory effect; – no effect)
\r\n\tThe purpose of this book is to provide the readers with an understanding of the characteristics of the crisis itself, recognize the wide range and multi-layer of the crisis from a real situation, give ideas on how to minimize the damage, and find ways to increase resilience in the future. To adapt to the rapidly and diversely changing world, the necessary experience and appropriate management for all kinds of crisis issues will be discussed as well. At the same time, it is intended to suggest elements such as verified scientific and empirical knowledge and applicable technologies; more effective risk management operation; modeling of the risks, manuals, management plans, and strategies.
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A close relationship between the key bodily regulatory systems, hypophysis-adrenal and hypophysis-thyroid systems, is fairly well-known.
However, the mechanisms of their interaction at different levels have not been conclusively established. This is of considerable interest due to glucocorticoids and thyroid hormones playing a key role in regulation of the most important systems of vital activity and adaptation. The role of glucocorticoids in regulation of thyroid cell function is interesting due to marked growth of thyroid pathology in different world’s regions, along with considerably improved iodine prevention [1], as well as an increased level of environmental stressogenicity. One should also note an increased tension in life of the individual and the society on the whole (psychological, social and other types of stress). The development of the society has actually created a new human environment with a raised level of stressogenic factors. The chronic stress –induced development of hypercorticism can play a significant pathogenetic role in the changed thyroid function which does not only depend on bodily iodine allowances.
Thyroid-stimulating hormone (TSH) [2, 3, 4], iodine [4, 5], thyroglobulin (ThG) [6], estrogens [7], cytokines [8] and other biologically active molecules play an important role in regulation of thyroid cell functions. It is interesting that deficiency of iodine, the key substrate for synthesis of thyroid hormones, decreases the activity of the HPA-axis. It was found [9] that rats with chronic iodine deficiency showed the absence of a normal circadian rhythm of corticosterone secretion and a weakened secretory rise of a corticosterone level under stress that remains to be diminished in amplitude during a month following restoration of the iodine status.
Thyroid cell function can be regulated by glucocorticoids via changes in the concentrations of the pivotal bioregulators: thyroid-stimulating hormone, TSH, iodine and thyroglobulin. The mechanisms and effects of these interactions call for further studies. Thyrocytes express glucocorticoid receptors, alpha (GR-alpha) and beta (GR-beta), which seem to play an important role in differentiation of thyroid cells since cells of thyroid adenoma demonstrated a decrease of mRA GR-alpha and an increase in GR-beta [10].
Relationships between the hypothalamo-hypophyseal-adrenal (HHA) and hypothalamo-hypophyseal-thyroid (HHT) systems were established at different regulatory levels. Administration of a thyrotropin-releasing hormone (TRH) was accompanied by a decreased adrenocorticotropic hormone (ACTH) level in blood serum of stressed rats [11]. Corticotropin-releasing hormone (CRH) increased plasma TSH and T4 [12]. Banos C. et al. [13] demonstrated that administration of 2 mg ACTH to healthy volunteers decreased the TSH response to TRH. These results characterize certain antagonism between TSH and ACTH.
TSH synthesis is determined by balance of positive regulation and negative regulation by TRH and triiodothyronine (T3), respectively; in addition, somatostatin and dopamine also exert inhibitory control (Diagram 1). Glucocorticoids decreased serum TSH in animals and humans. Administration of a high dose of dexamethasone not only suppressed TSH but also decreased the TSH response to TRH administration [14]; the suppressive effect of dexamethasone on TSH decreased in elderly people [15].
Administration of a single dose of hydrocortisone (500 mg) increased both TSH production and stimulation by TRH [16]; only long-term hypocorticism (Cushing’s disease) may be a cause for decreased TSH level. The earlier recovery (up to control values) of the diurnal rhythm of TSH than that of cortisol suggests that the TSH rhythm is not under the direct control of circulating cortisol [17]. In adrenalectomized rats the TSH level decreased in serum but not in the pituitary gland [18]. Glucocorticoids decrease blood serum TSH concentrations in humans and animals. Dexamethasone administration to hypothyroid rats decreased serum TSH; dexamethasone augmented a T3-induced decrease of TSH. However, changes in pituitary TSH α- and β-subunit mRNA concentrations were not found [19].
Effect of glucocorticoids on TSH. +, stimulatory effect; -, inhibitory effect; ↓ – weakening of stimulatory effect; ↑ – enhancement of inhibitory effect
Kakucska I. et al. obtained clearer results on the effects of glucocorticoids on the hypothalamo-pituitary-thyroid axis [20]. In the paraventricular hypothalamic nuclei of adrenalectomized rats, an increase in corticotropin releasing hormone (CRH) mRNA occurred in parallel to the increase (68.3%) in pro-TRH mRNA. On the contrary, administration of corticosterone or dexamethasone caused a marked decrease in CRH mRNA and pro-TRH mRNA by 43.2 and 73.3%, respectively. Insignificant changes in pro-TRH mRNA were found in the lateral hypothalamus.
Mechanisms of the stress-induced decrease in TRH/TSH secretion possibly involve glucocorticoids, cytokines, and opioids. Recently, a new regulatory mechanism, involving pituitary neuromedin B, gastrin-releasing peptide, and pituitary leptin, acting as local inhibitors of TSH release, has been proposed [21]. In vitro studies have shown that the lipocortin-1 (LC1) protein is a mediator of the glucocorticoid-induced suppression of TSH secretion by the anterior pituitary [53]. Treatment of anterior pituitary cells with 0.1 μM dexamethasone significantly increased the amount of LC1, associated with the outer surface of the pituitary cells and decreased the intracellular content of LC1. Addition of an N-terminal LC1 fragment (residues 1-188) decreased TSH release mediated by vasoactive intestinal peptide and forskolin, but failed to influence those initiated by 10 μM BAYK 8644, the calcium channel stimulator. The inhibitory action of dexamethasone was substantially reversed by a specific monoclonal anti-LC1 antibody [22]. The inhibitory effect of dexamethasone was used for monitoring of subclinical hypothyroidism in obese patients. Administration of TRH after dexamethasone increased the TSH level only in hypothyroid patients but not in euthyroid obese patients [23].
Iodine uptake is the most important function of thyroid cells; it is controlled by TSH, which stimulates 131I uptake in vivo and in vitro and also expression of sodium-iodide symporter (NIS) in the culture of human thyrocytes [24]. Sodium-iodide symporter (NIS) is located on the apical membrane of thyrocytes; its activity is coupled to Na+,K+-ATPase. TSH influences transcription of NIS gene through Pax-8 and factors activated by intercellular interaction during folliculogenesis [25]. High iodine doses directly inhibit iodide uptake by influencing regulation of NIS protein and mRNA expression [26, 27].
Immobilization stress and also ACTH administration to rats with pituitary damages increased 131I uptake by the thyroid gland in vitro [28]. Cultivation of FRTL-5 thyrocytes under hypoxic conditions was accompanied by increase iodide uptake [29]; heat stress (15 min at 45°C) eliminated this effect. Using culture of ewe thyroid gland follicles it was found that combination of TSH and 10 nM cortisol was optimal for stimulation of iodide uptake without additive and synergistic effects; this effect was also reproduced by combination of TSH with dexamethasone [30]. In addition, the stimulating effect of TSH was potentiated by physiological concentrations of insulin and insulin-like growth factors (IGF I and IGF II). Subsequent studies demonstrated a direct biphasic effect of hydrocortisone on metabolism of thyroid gland cells. Physiological concentrations of hydrocortisone (1—1000 nM) in a dose-dependent manner stimulated TSH- and 8-bromo-cAMP-induced iodide uptake, realized via increased production of cAMP and activation of cAMP-dependent metabolic pathways in the primary cultures of porcine thyrocytes [31]. The stimulating effect of hydrocortisone in combination with TSH was inhibited by the glucocorticoid antagonist RU486; the specific hydrocortisone effect appears to be mediated by a thyrocyte glucocorticoid receptor.
It is suggested that the stimulating effect of glucocorticoids on 131I uptake may be used for treatment for breast cancer [32] and prostate cancer [33]. Incubation of NP-1 cells with dexamethasone (10–8–10–6 M) caused a 1.5-fold increase in iodide uptake, and a 1.7-fold increase in expression of Na+/I–- simporter (NIS) mRNA and protein concentration; NP-1 cell death increased from 55 to 95%, thus suggesting increased cytotoxicity of 131I. These studies (employing clonogenic assay and nonradioactive proliferation assay) also revealed that treatment of NP-1 cells decreased proliferation of prostate cancer cells. Thus, stress (at least acute stress) may be considered as a factor activating iodide content in the thyroid gland; however, univocal solution of this problem requires further investigations because of multilevel effects of glucocorticoids on thyroid homeostasis
Single reports on the effect of stress or glucocorticoids on iodide oxidation by thyroperoxidase (TPO), thyroglobulin iodination and subsequent thyroid hormone secretion are available in the literature. Corticosterone administration for 10 days in three different doses (25, 50, 100 mg per 100 g of body weight) inhibited thyroid gland TPO of juvenile female turtles [34], but the mechanism of the inhibitory effect was not studied. Studies in this direction are especially important due to the key role of TPO in thyroid hormone biosynthesis.
The electron microscopy study of thyrocytes revealed accumulation of colloidal droplets in follicle cytoplasm; this suggests that prednisone may decrease basal secretion of thyroid hormones by inhibiting lysosomal hydrolysis of colloid in the follicular cells [35].
It is known that most of T3 effects are realized via nuclear receptors of thyroid hormones. T3 and glucocorticoid hormones synergistically interact in biosynthesis of growth hormone in the rat pituitary and in the T3-induced metamorphoses in amphibians. Glucocorticoid hormones potentiated metabolic effect of T3 [36]. Dexamethasone increased rat liver specific receptor binding of thyroid hormones. Dexamethasone administration to adrenalectomized rats increased the concentration of protein and mRNA of beta 1 receptor [36]. Molecular studies employing transfection of COS-7 cells revealed that dexamethasone increased transcription activity of thyroid hormone receptor beta 1 promoter [36].
Brain, liver, kidney, heart, muscles, and immune system are the most important targets for thyroid hormones. It is possible that glucocorticoids control tissue levels of T3. Acute stress (footshock) increased the brain T3 content in male and female rats by 12—19% [37]. Two days of total water and food deprivation as stress increased the thymus lymphocyte T3 content in weanling and adult female rats [38], which was normalized after 48 h [39]. It is known that thyroxine (T4) is the main hormone produced by the thyroid gland, however, since it does not exhibit biological activity and therefore thyroxin may be considered as a prohormone or a plasma storage form of thyroid hormones, which plays an important physiological role. A family of selenocysteine oxidoreductases known as iodothyronine deiodinases (D) plays the major role in T4 activation. Three types of these enzymes (mainly determining realization of the hormonal effect of thyroid hormones) have been identified. Their localization and activity are tissue-specific (Scheme 2, 3).
Glucocorticoids exhibit differentiated tissue- and age-specific effects on various tissue deiodinases [40, 41]; they also regulate deiodinases during embryogenesis. Dexamethasone administration to pregnant ewes increased activity of DI in the fetal liver and decreased DIII activity in fetal kidneys [42]. In 20-day-old fetuses, glucocorticoids had no effects on circulating thyroid hormone levels despite their clear decrease in the activity of hepatic and renal deiodinases and an increased activity in the brain, thereby indicating that in this age thyroid circulating thyroid hormone levels are more dependent on thyroidal secretion than on peripheral deiodination. In 5-day-pups, dexamethasone increased blood T3 and T4 and DII activity in the liver, kidney but not in the brain; however, in 12-day-old pups, the dexamethasone effects were maintained only on liver and kidney DIII activity [43].
Tissue distribution of deiodinases
Forms of thyroid hormone utilization by various
Types of deiodinases | Target tissues | Effect | Reference |
DI | fetal liver, ewes | ↑ | [42] |
DIII | fetal kidneys, ewes | ↓ | [42] |
DIII | 5-day-pups liver, rat | ↑ | [43] |
DIII | 5-day-pups kidneys, rat | ↑ | [43] |
DIII | 5-day-pups brain, rat | – | [43] |
DIII | brown adipose tissue, rat | ↓ | [58] |
DII | brain, rat | ↑ | [44] |
DI | liver, rat | ↓ | [51] |
DI | kidneys, rat | ↓ | [52] |
DI | hepatocytes in vitro | ↑ | [54] |
Effect of GC and stress on activities of various types of deiodinases in rat tissues (↑ – stimulatory effect; ↓– inhibitory effect; – no effect)
Effects of stress on deiodinase activity in various tissues still require better elucidation. The most significant effect of glucocorticoids was found on brain DII activity. Even mild, short-term stress (intraperitoneal injection of saline, intragastric intubation, and two different forms of handling (being grasped as for intraperitoneal injection and being moved from one cage to another, and a 2-h period spent in a slowly rotating drum) caused a significant increase in brain DII activity [44], this was accompanied by a 300%-increase in T3 concentration. These effects were not found in the liver and no changes of DI activity were found in the brain and liver. Dexamethasone caused up-regulation of DII activity [45]. Administration of steroidogenesis inhibitors (aminoglutethimide and metyrapone) to rats decreased adrenal DII activity both in physiological rest and under stress [46]; this suggests normal corticosterone levels required for a deiodinase response to the stress treatment. It appears that the glucocorticoid regulation of DII is the most differentiated. Recent in vitro data obtained using mouse and rat pituitary cells demonstrated that addition of glucocorticoids increased the activity of this enzyme and its mRNA [47], whereas the opposite effect was obtained in mouse mammary gland epithelial cells [48]. In the AtT-20 mouse pituitary tumor cells, glucocorticoids and CRH stimulated expression of mRNA and activity of DII [49]. Effects of glucocorticoids, found in experiments on cultivated hypophyseal cells, confirm their important stimulatory role in the metabolism of thyroid hormones in the CNS.
A decrease in blood thyroid hormones and TRH mRNA seen in fasting and food deprivation was accompanied by the increase DII activity and DII mRNA. Studies of mechanisms of DII activation during fasting revealed that the decrease in leptin levels plays a permissive role during glucocorticoid-induced regulation of the DII enzyme [50].
There are contradictory data on the effects of glucocorticoids on DI activity in various tissues. Cold stress of rats either for 24 h or 28 days (as well as that combined with immobilization) significantly reduced DI activity in the liver [51]. Immobilization of rats for 6 - 8 h was accompanied by the decrease in DI activity in the liver and kidneys; this was attributed to the decrease in the enzyme activity rather than to decreased substrate availability because serum T4 concentration remained unchanged [52]. In adult rats, glucocorticoids decreased DI activity in the liver [53]. In vitro studies on the cultured rat hepatocytes revealed the opposite effects: glucocorticoids increased DI activity and expression of DI mRNA [54]. In kidney NRK 52E cells, dexamethasone increased DI activity and expression of DI mRNA, while in cultured pituitary tumor cells, glucocorticoids did not influence DI mRNA [55]. In the fish
The decrease in plasma T3 and the increase in rT3 concentrations observed in stress may be associated with glucocorticoid stimulation of DIII [57]. Regulatory mechanisms of effects of thyroid hormones in various tissue cells have not been conclusively established. Glucocorticoids decreased DIII expression in rat brown adipose tissue [58]. The study of deiodinase activities in human cell lines revealed that estradiol increased DIII activity in ECC-1 cells, dexamethasone inhibited DIII in WRL-68 cells only in the presence of fetal calf serum in the medium [59]. Dexamethasone in a dose-dependent manner decreased the stimulatory effect of T3 on ICAM-1 protein in human ECV 304 cells [74].
All these results indicate that glucocorticoids modulate effects of thyroid hormones by influencing deiodinase activity in various target tissues. They cause significant increase of DII activity in the brain (and thus increase brain T3 level); stress exhibited inhibitory effect on DI activity in the liver and kidneys. Nevertheless, mechanisms underlying glucocorticoid regulation of T4 deiodination in various tissues require further investigation.
Taking into consideration the multilevel effects of glucocorticoids on the thyroid status and peripheral metabolism of thyroid hormones, a study of functional activity of the thyroid gland under conditions of adrenal impairments appears to quite reasonable.
Adrenalectomy in rats increased thyroid gland stimulation by TSH and its secretory activity [60]. In patients with adrenal insufficiency cessation of replacement glucocorticoid therapy resulted in an increase of T3 and a decrease of (reversive triiodothyronine) rT3 concentrations, whereas the level of T4 and TSH remained basically unchanged [61].
There are clinical case reports on impairments of thyroid function in patients with hypercorticism before and after adrenalectomy and with adrenal insufficiency. The state of the pituitary-adrenal axis mainly determines the thyroid status in humans. Under hypercorticism in patients with Cushing’s syndrome there were decreased serum concentrations of thyroid hormones and TSH; in addition, in 56.2--66.6% there was a prevalence of thyroid nodular disease; this was significantly higher than in the control group [63]. Long-term hypercorticism in patients with Cushing’s syndrome was accompanied by inhibition of basal and TRH-stimulated TSH secretion [62]. These patients had an attenuated pituitary response to TRH administration and there was a negative correlation between plasma levels of TSH and cortisol (but not T3); after convalescence the reaction to TRH normalized [64]. There was a single case report on the development of Graves’s disease characterized by pronounced hyperthyroidism after a successful surgical operation in a patient with Cushing’s syndrome [65]. Authors suggest that suppression of hypercorticism activated latent autoimmune processes in the thyroid gland. Graves’s disease with hyperthyroidism manifestations was diagnosed 9 months after unitaleral adrenalectomy in a woman with Cushing’s syndrome [66]. In some patients subjected to surgical adrenalectomy for hypercorticism transitory dysfunction of the thyroid gland with symptoms of hypo- or hyperthyroidism developed [67]. Silent thyroiditis developed in a female patient after unilateral adrenalectomy for treatment of Cushing’s syndrome followed by a gradual tapering of replacement dose of prednisolone to 5 mg/day; thus thyroiditis was characterized by low TSH, increased thyroid hormone levels, extremely low iodine uptake and increased titers of antimicrosomal and antithyroglobulin antibodies [68]. Recent observations have demonstrated that secondary hypothyroidism and hypercalciemia are consequences of the glucocorticoid deficiency developed after adrenalectomy for Cushing’s syndrome [69].
In 103 patients with ACTH deficiency Murakami T. et al. [70] found signs of hypothyroidism (a decrease in free T3 and T4 concentrations, high TSH) and characteristic symptoms of clinical manifestations of thyroid insufficiency (cold intolerance, muscle rigidity, loss of interest in life). After hydrocortisone therapy all signs of impairments of the pituitary-thyroid axis disappeared in more than 70% cases; this suggests that glucocorticoid insufficiency is one of reasons underlying thyroid dysfunction. A high TSH level was found in patients with Addison’s disease; administration of glucocorticoids caused dose-dependent inhibition of TRH-induced stimulation of TSH secretion; it is possible that glucocorticoids regulate pituitary sensitivity to TRH [71].
Moderate hypothyroidism is a consequence of exogenous or endogenous hypercorticism. In prepubertal children with nonclassical congenital adrenal hyperplasia (NCCAH) TSH and cortisol were secreted in a pulsatile and circadian fashion with a clear nocturnal TSH surge; daytime TSH levels were lower in the NCCAH group than in control children. The cross-correlation analysis of the 24-h raw data demonstrated that TSH and cortisol were negatively correlated, with a 2.5-h lag time [72].
Adrenalectomy not only reduced plasma corticosterone levels to almost zero, but also decreased plasma T3 and T4 levels, but diurnal rhythms of the HPT axis did not depend on rhythms of the HPA axis [73]. In pregnant female rats adrenalectomized on gestation day 8 there was a decrease in TRH mRNA, increase in serum TSH, and a decrease of T3 only in females [74]; it appears that maternal glucocorticoids determine the development of the hypothalamic-pituitary-thyroid axis in progeny.
Conclusion. The analysis of the literature data shows that the role of glucocotricoids in regulation of iodine metabolism in thyroid cells as well as their effects on the HHT system have not been conclusively established. Very few data are available on early changes in thyrocyte iodine metabolism induced by psychoemotional stress which characterize triggering of adaptation in metabolic systems. The idea is very important of the mechanisms of iodine oxidation and organification and the function of the key enzyme in thyroid hormone biosynthesis, TPO, with the activity governing synthesis of thyroid hormones. This seems to be especially topical in relation to increased levels of stressogenic factors in human environment and functions of all the systems under the stress of hypocoticism.
The goal of the above research is to assess the effects of glucocorticoids on the activities of the main steps of thyroid iodine metabolism and to study the features of iodine metabolism under exposure to short-term and chronic psychoemotional stresses.
Administration of high doses of potassium iodide to animals with normal and reduced glucocorticoid status.
To measure the contents of protein-bound and free iodine in the thyroid homogenate, the proteins were sedimented with 5.2% perchloric acid and 0.125 ml of the supernatant was used to determine free iodine concentration, the sediment was used to measure protein-bound iodine concentration. After the separation of the iodine fractions, the procedure of measurement corresponded to that described above (I total).
Under psychoemotional stress, the corticosterone content was most elevated (405.8-447.7%) for 15-60 min. It was decreased following 2 hours after stress cessation (2.9-fold) and increased after 6 hours (2.1-fold) at the post-stress period (Fig. 1). Analysing the wave-like dynamics of changes in corticosterone concentration at the post-stress period, we should note that the rats were stressed in the morning (9.00 to 10.00 a.m.) and the rise in corticosterone concentration at the post-stress period was not related to its circadian rhythm (since the circadian rhythm of corticosterone is characterized by maxima per 20.00 hour). The corticosterone concentration was observed to increase in the afternoon (16.00 p.m.) after 6 hours following the post-stress period, and this elevation of serum corticosterone is a characteristic manifestation of a regulatory feedback mechanism. As a response to a marked reduction of corticosterone concentration after 2 hours following stress, the ACTH concentration elevated, which induced a new wave in increasing blood and adrenal corticosterone concentration that is a manifestation of the adaptation syndrome.
Blood serum (A) and adrenal (B) corticosterone concentrations in rats at acute stress and post-stress periods, after exposure to psychoemotional stress (n=8).
The dynamics of changes in the parameters characterizing thyroid iodine metabolism was of a wave-like pattern, which indicates a pronounced response of the rat thyroid to stress. This was most pronounced for changes
in the index If, which is quite explicable. During 15-30 min of stress the thyroid total iodine concentrations remained unchanged (176.9-234.9 µg/g tissue). However, after 60 min, its content was 39.3% decreased in comparison with 15-and 30-min stress (Fig. 2А). During the acute stress phase (15-30 min), intensification of iodide organification was noticed: the concentration of its protein-bound fraction was 37.6% elevated, and the ratio of protein-bound I to total I was 1.2-fold increased (Fig. 2B). The 70.5% elevation of free iodide concentration in the thyroid gland (Fig. 2C) was probably due to activation of proteolytic processes in thyroglobulin and thyroid hormone formation. We cannot also exclude activation of iodine uptake with consideration for the absence of iodine supply to the body during stress, which can be due to increased activities of tissue deiodinases. Along with this, in spite of the evidence for Na+/I–- simporter expression in some cells (salivary and mammary glands) the literature lacks information about other iodine depots in addition to the TG. After 60-min stress, the thyroid showed diminished concentrations of free and protein-bound iodine, which seemed to be a consequence of highly active secretory processes and inhibition of iodine organification, TPO activity (Fig. 3) remained at a level of control values during 30-min exposure to stress, decreasing by 34.8% after 45 min, which was accompanied by a 16.8% reduction of protein-bound I concentration. The stress- induced drop in TPO activity can be due to changed kinetic parameters of the enzyme. TPO was found to be sensitive to elevation of ROS concentrations and aldehyde products of lipid peroxidation in thyroid cells [81]. Moreover, an important role in this case can be played by a decreased TSH level that regulates key processes in the TG. Taking into consideration the antagonistic relations between ACTH and TSH, one can suggest the metabolic changes in the TG to be caused by a stress-induced increase of the ACTH level which can induce a decrease of TSH production.
The correlation analysis of the results did not show a correlation between thyroid TPO activities and glucocorticoid levels in the blood serum and adrenal glands. After 60-min stress, a negative correlation was found between the total thyroid iodide and adrenal corticosterone (r= –0.952, p=0.003). In the control group, the content of adrenal corticosterone positively correlated with the protein-bound I to total I ratio (r=0.955, p=0.01), which indicates involvement of glucocorticoids in regulation of iodine homeostasis in the TG.
The decrease in corticosterone concentration after 2 h following the stress exposure was followed by activation of TPO (3.6-fold) as opposed to 60-min stress and control (3.4-fold). The TPO activation at the post-stress period suggests the presence of regulatory mechanisms for its activity which are related to a corticosterone level since it is at that period that its blood and adrenal concentrations were diminished most appreciably. The subsequent elevation of corticosterone concentrations in 4 and 6 h within the recovery period was followed by a dramatic decrease of thyroid TPO activity.
Rat thyroid total (A), protein-bound (B), and free (C) concentration of iodine during acute stress and post-stress periods. A, B, C, D, E, F, G represent respective designations for groups of animals. B, C, E. F represent statistically significant change in the parameter (p< 0.05) compared to the corresponding group
Rat thyroid TPO activity at acute stress and post-stress periods.A, B, C, D, E, F, G represent corresponding designations for animal groups.A, B, C, D, E represent statistically significant changes in parameter (p<0.05) compared to the corresponding group.
Rat blood iodine concentration at acute stress and post-stress periods.A, B, C, D, E, F, G represent corresponding designations for animal groups.A, B, C, D, E, F represent statistically significant changes in the parameter (p<0.05) compared to the corresponding group.
The iodine status restoration after the 2- h post-stress period is characterized by elevated concentrations of total I, protein-bound I and free I (55.5, 38.3 and 40.8%, respectively). A marked restoration to the control values of all the thyroid parameters studied was noticed after 4-6 h following the cessation of stress exposure. Under physiological conditions, the blood serum iodine content was not high (approx. 20 µg/l). However, acute stress diminished its level (52.3%) at the post-stress recovery period (after 6 h following stress), which can be a consequence of restoration of the iodine status in the thyroid (Fig. 4).
Control | Stress, 15 min | Stress, 30 min | Stress, 45 min | |
Groups | А | B | C | D |
Т4 total, nM | 59.4±4.1 | 60.6±3.6 | 60.5±2.4 | 59.09±4.4 |
Т3 free, nM | 2.9±0.22 | 2.9±0.21 | 2.3±0.12 | 2.3±0.20А,B |
Stress, 60 min | Stress, 60 min + 2-hour post-stress periods | Stress, 60 min + 4-hour post-stress periods | Stress, 60 min + 6-hour post-stress periods | |
Groups | E | F | G | H |
Т4 total, nM | 58.7±3.5 | 59.1±2.2 | 64.8±6.0 | 51.6±4.5 |
Т3 free, nM | 2.1±0.21 А,B | 2.7±0.29 | 2.1±0.13А,B,F | 2.0±0.26 А,B,F |
Rat blood T4 and T3 concentrations at acute stress and post-stress periods
The stress exposure did not produce significant changes in the concentration of blood serum total T4. However, the free T3 content lowered at the 30th minute of stress and remained to be 18.6 to 28.5% lowered throughout the experiment. It was not until 2 hours later that it increased up to the control values (Table 1).
Our findings show involvement of the TG in adaptation of the body to acute stress. We should note the thyroid ability to a rapid recovery of the iodine status at the post-stress period. Throughout a short period of time (15-30 min), the acute stress induced activation and uptake of iodide and thyroid hormone secretion.
However, oxidation of iodide was inhibited and the contents of total I, protein-bound I and free I were decreased after 45 and, significantly, after 60 min.
The 60-min exposure to psychoemotional stress revealed a negative correlation between the concentration of total I in the thyroid and the corticosterone concentration in the adrenals (r= –0.952, p=0.003). This shows that overproduction of glucocorticoids under stress induces a decrease of thyroid iodine content, resulting in a negative iodine balance at the post-stress period. The 2-hour recovery period is characterized by a pronounced activation of thyroid iodine metabolism (TPO activity rose over 3-fold), and the partial restoration of the thyroid iodine status (after 4-6 hours) was accompanied by a decreased blood serum iodine content.
The following correlations were established at the post-stress recovery period:
after 4 hours, the blood serum iodide concentration negatively correlated with the corticosterone concentration (r= –0.831, p=0.040);
after 6 hours, there was a highly significant correlation (r=0.937, p=0.006) between the blood corticosterone level and the ratio of protein-bound I to total I;
The data for the recovery period demonstrate that the blood corticosterone level can be viewed as a factor inducing a decrease of blood iodine concentration in rats.
Thus, the short-term stress (5-30 min) induced activation of biosynthesis and secretion of thyroid hormones. The most important regularity of the post-stress period is restoration of the thyroid iodine status due to activation of iodine uptake and organification as well as the presence of a close negative correlation between the thyroid concentration of I total and the adrenal corticosterone concentration (r= –0.956, p=0.003). After 6 h of the recovery period, the concentration of blood corticosterone was positively correlated to the ratio of protein-bound I/total I in the TG (r=0.937, p=0.006). A close correlation found between the levels of corticosterone and iodine in the thyroid gland may primarily show possible regulatory effects of glucocorticoids on iodine uptake. But no effects of glucocorticoids on TPO were found, which definitely indicates the absence of direct interactions. However, elevation of thyroid iodine concentration, induced by glucocorticoids, can activate TPO.
The above findings show that the exposure to stress induced a marked imbalance in the thyroid iodine status which was rapidly recovered at the post-stress period due to the decreased blood serum iodine concentration and that the restoration of the thyroid iodine status is most closely related to the glucocorticoid status.
We studied the effects of 30-min psychoemotional stress on the iodine metabolism after administration of three daily doses of potassium iodide (KI was administered directly before the exposure to stress). The administration of three daily doses of KI increased 4.3-fold the blood iodine level within 6 hours. This concentration was decreased to the control values after 24 h (Fig. 5). In the group of rats subjected to stress, the iodine content also increased (296.7%) after 30 min following the administration of 3 daily doses of KI. In contrast to the control rats, the stressed rats showed a pronounced maximum of blood iodine concentration after 6 h (839.4% elevation, 170.7µg/l). After 24 h, the level of blood iodine in the stressed rats did not differ from that in the controls. The stress-induced changes in the kinetics of blood iodine concentration are a consequence of a disturbed regulation of iodine homeostasis. The dramatic, over 800%, elevation of blood iodine concentration can be due to an imbalance in the activity of its uptake: lowering of uptake in the TG and activation of uptake in the gastrointestinal tract at the post-stress period. It should be noted that it is at that period that the rat blood showed an increase in the corticosterone concentration (Table 2). A comparative examination of the curves characterizing changes in thyroid iodine concentrations in two animal groups (Fig. 5 B) shows that after 24 h, the thyroid iodine concentration elevated 1.7-fold in the control rats and remained essentially unchanged in the stressed rats (1.2-fold increase).
The 30-min psychoemotional stress leveled off the increase in the thyroid iodine status after administration of 3 daily KI doses. The changed concentrations of thyroid protein-bound I and free I (Fig. 5, B and C) reflect changes in TPO activity in the thyroid gland (Fig. 5D). The administration of 3 daily KI doses was accompanied by activation of its organification in the group of control rats within 1 h (the level of protein-bound I was increased by 54.1%) and elevation of its concentration by 74.3% after 24 h.
Effect of 30-min exposure to psychoemotional stress on iodine content in rat blood serum (A), total iodine (B), protein-bound iodine (C), activity of TPO (D) in rat thyroids after administration of 3 daily doses of KI within 24 h of the post-stress period
The dynamics of changes in TPO activity in the stressed animals treated with 3 daily doses of KI had an essentially opposite character in comparison with the controls (Figure 5D). The post-stress increase in TPO activity after 1 h was accompanied by 41.5% decrease of its activity by 6 h as opposed to the initial level. As compared to the control animals, the activity of TPO in the thyroid of the stressed rats diminished over 2-fold, whereas the concentration of protein-bound I decreased 1.4-fold after 24 h following the administration of 3 daily KI doses.
The data obtained indicate that the 30-min exposure to stress after the administration of 3 daily KI doses changed the kinetics of iodine metabolism in rats within 24 h of the post-stress period. These data reflect complex relationships between the regulatory effects of the pituitary-thyroid and pituitary-adrenal systems as well as the whole complex of metabolic stress changes in the organism in respect to the key steps in thyroid iodine metabolism. Stress enhances the iodine inhibitory effect.
Before KI administration | After KI administration | |||||
30 min | 1 h | 3 h | 6 h | 24 h | ||
Blood corticosterone, nM | 302.8±28.5 | 1279.1± 101.6* | 1580.4± 118.9* | 2135.8± 260.7* | 1778± 194.9* | 472.7± 47.4 |
Before stress | After administration of KI and exposure to stress | |||||
30 min | 1 h | 3 h | 6 h | 24 h | ||
Blood corticosterone, nM | 302.8±28.5 | 2571.6± 282.7* | 867.8± 104.5* | 664.3± 100.5* | 1661.8± 272.5* | 697.7± 75.9* |
Effect of 30-min stress exposure on corticosterone concentration in rat blood after administration of 3 daily doses of KI within 24 h of post-stress period
The most pronounced stress-induced changes in iodine metabolism after administration of physiological KI doses (3 daily doses) are characterized by:
abnormal kinetics of changes in blood iodine concentration within 24 h after administration of KI, which was manifested by accumulation of blood iodine (839.4% elevation) after 6 h at the post-stress period;
changes in the kinetics of iodine uptake and oxidation in the TG, which results in a decreased content of total I and protein-bound I in thyroids of stressed rats after administration of 3 daily doses of KI as opposed to the control group which showed an increase of these parameters.
A research was carried out into a short-term stress effect (daily, over a long period of time) on the activities of the key steps in iodine metabolism in the rat thyroid. The data obtained indicate that daily 20-min exposure to stress (4 weeks) induced pronounced changes in thyroid iodine metabolism.
Figure 6 shows that the total thyroid iodine content in stressed animals was elevated 1.97- fold as opposed to controls and amounted to 491.8±15.5 µg/g tissue. The contents of its protein-bound and free fractions corresponded to 329.9±8.3 µg/g tissue and 161.8±18.4 µg/g tissue, which was 1.6-and 3.1-fold higher compared to the controls. The increased thyroid iodine concentration was accompanied by a changed ratio of its various fractions (Table 3). The 2-fold elevated free I/protein-bound I ratio and the lowered protein-bound I/total I ratio (1.18-fold) are indicative of a lowered efficiency of thyroid iodine organification under stress.
Effect of 4-week psychoemotional stress (20 min, daily) on contents of total I, protein-bound I and free I in the rat thyroid
Indices | Control | Stress |
Free I/protein-bound I | 0.26±0.034 | 0.50±0.066* |
Protein-bound I/total I | 0.79±0.021 | 0.67±0.028* |
Urinary I, µg/l | 17.9±2.29 | 22.2±1.94 |
Effect of short-term daily psychoemotional stress on the ratio of different rat thyroid iodine fractions and urinary iodine excretion
Indices | Control | Stress |
T4 total, nM | 49.2±2.82 | 51.7±3.34 |
T3 total, nM | 1.2±0.06 | 1.3±0.07 |
TPO, µmol/min x g tissue | 23.4±2.70 | 20.9±2.91 |
Thyroid weight, mg | 15.7±0.63 | 13.3±0.47* |
Thyroid cytosolic protein, mg/g tissue | 158.5±3.6 | 137.9±5.3* |
Effect of short-term daily psychoemotional stress on the concentration of blood thyroid hormones, TPO activity, thyroid weight and thyroid protein concentration
No changes were found in the activity of TPO, the key enzyme of thyroid hormone biosynthesis (Table 5). The thyroid weight in stressed rats was lowered by 18%, whereas the protein concentration in the thyroid cytosolic fraction – by 13%. The blood thyroid hormone content at the post-stress period was maintained at the level of control values (Table 5), the level of corticosterone was increased by 32.8% (Table 6) and the weight of the adrenal glands rose by 13%.
Indices | Control | Stress |
Blood serum corticosterone, nM | 383.2±65.9 | 509.2±90.0# |
Adrenal corticosterone, nmol/g tissue | 152.8±17.9 | 176.2±30.8 |
Adrenal weight, mg | 46.6±1.9 | 52.7±2.5* |
Effects of short-term daily psychoemotional stress on adrenal weight, blood corticosterone concentration and corticosterone concentration in rat adrenals.
As our data show, stress caused multidirectional changes in the activities of the key steps of thyroid iodine metabolism. The elevated content of the total and free iodine is a consequence of stimulation of its absorption at the post-stress period [28]. The decreased efficiency of iodine organification may be due to TPO inhibition and lowering of thyroglobulin concentration. The stress-induced lowering of thyroid TPO activity was shown earlier. As Table 7 demonstrates, the repeated exposure to short-term stress during 7 days and over was accompanied by a decrease of thyroid TPO activity both directly after exposure to stress (46.9-56.6%) and after 24 h following its cessation (59.2-60.7%).
Index | Control | Stress, 7 days | Stress, 14 days | ||
TPO, µmol/min g protein | 153.5±15.2 | 81.4±21.43* | 60.2±4.9* | 66.6±9.4* | 62.6±18.22* |
Effect of short-term (20 min) psychoemotional stress (daily, 7, 14 days) on thyroid TPO activity
Effects of stress on iodine oxidation and organification in thyroid cells have not been virtually investigated. We found only one study on female tortoises. Thyroid TPO activity in young female tortoises was lowered after ten-fold administration of corticosterone (25, 50, 100 µg/100 g body weight) [34]. Nothing has been known of the effect of stress on thyroglobulin biosynthesis. However, the diminished level of thyroid protein-bound I can be stipulated by its impaired biosynthesis. Moreover, a consequence of stress was a 13%- decreased total protein concentration in the thyroid cytosolic fraction. This certainly applies to thyroglobulin, taking into consideration that it amounts to 75-80% and up of the total thyroid protein.
The main regulator of TPO and thyroglobulin synthesis is TSH whose secretion is inhibited by glucocorticoids [20], which can induce depression of thyroid hormone synthesis. Stress is suggested to cause a decrease of TSH production via pituitary neuromedin B, gastrin-releasing peptide and pituitary leptin acting as local inhibitors of TSH release under stress [21]. It was found that lipocortin -1 is a mediator of glucocorticoid-induced suppression of TSH secretion by the anterior lobe of the pituitary gland [21].
The inhibitory effect of stress seems to be followed by activation of thyroid metabolism at the post-stress period and the restoration of thyrocyte function is related to activation of thyroid hormone secretion, which is confirmed by resorption of colloid and depletion of thyroid follicules. These conditions disturb the thyroglobulin synthesis/secretion balance. As a result, the thyrocytes and follicular lumen accumulate a considerable amount of non-organified iodine, which is confirmed by our findings. Stress decreases thyroid weight, which can be both a consequence of its hypersecretion and destructive processes; the mechanism of this change is certainly interesting.
The experimental findings show that a consequence of the repeated exposures to psychoemotional stress are pronounced structural and metabolic changes in the TG that are characterized by an elevated iodine content, a decreased extent of its organification, development of oxidative stress and lymphocyte infiltration along with the impaired thyroid follicular structure. The mechanisms of the regularities found call for detailed research and are of great interest to disclose the pathogenesis of autoimmune thyroiditis, thyroid carcinoma as well as the contribution of the thyroid component to development of endemic and nodular goiters.
There are presently no unambiguous data on the role of stress in induction of thyroid pathology in humans. Individual cases have been described of autoimmune thyroiditis developed after surgical treatment of hypercorticism (Cushing’s syndrome) [65]. A pronounced stress effect can be an onset of Graves’ disease [82]. There were reports about relationships between stress and Hashimoto’s thyroiditis [83]. According to Polish researchers [84] secondary adrenal deficiency can be a cause of autoimmune thyroid diseases in humans: stress affects the immune system, and immunologic modulations are considered to be a factor inducing autoimmune thyroiditis in genetically prone individuals [85]. Stress hormones, affecting antigen-presenting immune cells, can influence the differentiation of bipolar T-helpers from Th1 to Th2 phenotype, which causes suppression of cellular immunity and enhancement of humoral immunity. Stress is likely to contribute to the development of Graves’ disease by shifting the Th1/Th2 ratio from Th1 to Th2. Recovery after stress or immunosuppressive effect of pregnancy can induce a “reverse shift” in Th2 → Th1, causing autoimmune (sporadic) thyroiditis [85].
Stress-induced impairment of thyroid function characterized by development of oxidative and iodine stress is likely to be viewed as a main mechanism of thyroid ageing in humans and, consequently, to be a cause of diseases of age related to thyroid deficiency [86, 87]. Further studies are needed to disclose the mechanisms of stress-induced impairment of thyroid functions.
The above findings confirm that stress considerably changes thyroid iodine metabolism, affecting its uptake and organification. Since all the experimental studies were carried out using models characterizing hyperfunction of the adrenal glands (stress), a comparative investigation of iodine metabolism in rats with adrenal deficiency should be done in order to establish the biochemical mechanisms.
The glucocorticoid status in rats was assessed by the level of corticosterone which was lowered 4.4 to 6.4-fold in adrenalectomized (AE) rats compared to controls. Adrenal deficiency was a cause of 44.2 % - decreased thyroid TPO activity (Fig. 7B). The administration of 1000 daily doses of KI (a dose=70 mg/kg) decreased thyroid TPO activity in the TG of the control rats and elevated it in the glucocorticoid-deficient animals with to the control values. The administration of 1000 daily doses of KI was accompanied by increases in thyroid total I (42.2%), protein-bound I (19.1%) and free I (90.6%) in AE rats (Fig. 8). This indicates that under hypocorticism the regulatory mechanisms for thyrocyte functions can be disturbed by high iodine doses.
Effect of single administration of 1000 daily doses of KI on concentration of blood serum corticosterone (nM) (A) and TPO activity (µmol/min x g protein) in thyroids of intact and AE rats (B)
Effect of single administration of 1000 daily KI doses on contents of total I, protein-bound I and free I in thyroids of rats with normal and decreased glucocorticoid statuses
The blood thyroid hormone levels in AE rats were above the control values (27% for T4 and 35% for T3), but administration of KI lowered the concentrations of T4 by 41.1% and T3 by 34% compared to the AE animals. T4 was 29% decreased even in comparison with the controls (Fig. 9).
Effect of single administration of high KI dose on concentrations of total blood serum T4 and T3 in rats with normal and decreased glucocorticoid statuses
Index | Control | 1000 daily doses of KI | АE | АE+1000 daily doses of KI |
А | B | C | D | |
TBARS, nmol/g tissue | 131.2±8.9 | 212.5±22.9А | 150.4±15.0 | 115.5±9.6B,C |
Cаtalasa, μmol/min×g protein | 36.8±1.3 | 40.0±1.6 | 32.2±0.8А,B | 33.7±1.7B |
SOD, activity u./min×g protein | 43.2±4.2 | 56.8±1.4А | 51.1±2.0А,B | 48.9±2.9B |
GR, μmol/min×g protein | 24.0±1.2 | 22.7±1.0 | 26.7±1.0B | 25.5±1.5 |
Effect of single administration of 1000 daily doses of KI on TBARS levels and antioxidant enzyme activities in thyroids of rats with normal and decreased glucocorticoid statuses
In contrast to the rats with the normal glucocorticoid status, in which the administration of KI inhibited the thyroid function and induced activation of oxidative processes (62.0% elevation of TBARS concentration, 54.3% activation of SOD), the adrenalectomized rats did not show activation of lipid peroxidation (the level of TBARS was decreased by 23.2%, Table 8).
The AE animals demonstrated elevated concentrations of T3 and T4 in the blood serum (Fig. 9). These changes seemed to be caused by alterations in thyroid iodine metabolism since the contents of its different fractions did not change under decreased glucocorticoid status (Fig. 8). It was found earlier that AE caused enhancement of liver thyroxin-binding globulin synthesis and its binding capacity in the blood [88] as well as inhibition of the peripheral metabolism of thyroid hormones. Enhancement of deposition of blood thyroid hormones and, consequently, inhibition of their metabolism may cause elevation of thyroid hormone concentrations.
Most interesting changes were found after administration of high iodine doses to rats. In contrast to control animals with the characteristic acute Wolff – Chaikoff’s effect, we did not observe inhibition of iodide organification in this group. Moreover, a pronounced lowering of T4 and T3 concentrations in the blood serum of AE rats after the administration of high iodine doses suggests that the cause of the absence of the Wolff-Chaikoff’s effect under hypocorticism can be impaired maturing of the prohormone, thyroglobulin, and abnormal secretion of thyroid hormones to the blood, which provides for elevated concentration of protein-bound I in this group. Elevated TSH concentrations and enhanced NIS expression and, consequently, increased uptake of iodide absorption by the TG are also possible.
Our findings show that the effects of the single administration of the high KI dose on the activity of hormonogenesis in thyroids from normal and AE animals are multidirectional. Thyroids from the intact rats show inhibition of iodide organification accompanied by induction of oxidative stress, whereas the hypocorticoid rats demonstrate a reverse effect: activation of iodide uptake and organification as well as a decrease in the intensity of lipid peroxidation. These results are of a considerable interest in relation to some clinical studies which prove that impairments in the glucocorticoid status can be linked to development of autoimmune thyroid diseases. Lowering of the functional activity in the hypophyseal link (ACTH) and/or the adrenal (cortisol) link was noted in patients with autoimmune tyroiditis [89, 90]. It was shown that autoimmune tyroiditis and diabetes mellitus are developed on the average 7 years after autoimmune damage of the adrenal glands [91]. In patients suffering from hypercorticism of different genesis, AE contributes to development of autoaggression in their thyroids [68, 66, 92]. It is suggested that puerperal thyroiditis, as a consequence of a temporary decrease of the glucocorticoid status in females at the puerperal period [93], is due to ACTН-releasing hormone inhibition of the synthesis and secretion of maternal hypothalamic ACTH-releasing hormone and that this inhibition is of a placental origin. It should be mentioned that impaired functional activities of the pituitary-adrenal axis are also noted in other autoimmune diseases [94]. The mechanisms of the regularities found certainly require further studies since the literature lacks information on this problem.
Glucocorticoid deficiency is a cause for impairments of the adequate regulation of the thyroid status and thyroid iodine metabolism. It was interesting to study the properties of the iodine metabolism after its repeated administration to rats with adrenal deficiency.
After 2 weeks following AE, the blood serum thyroid hormone concentrations in operated animals were partially restored and amounted to 23.7-42.3% of the control values (Fig. 10)
Effect of 14-day administration of 1-500 daily doses of KI on blood serum corticosterone concentration in AE rats.
Studies on the thyroid iodine metabolism showed that repeated administration of high KI doses resulted in 46.9-115.7% increased concentrations of total I and caused 120.4 to 223.9% elevations of free I in all the experimental groups (Fig. 11). Glucocorticoid hormones are likely to inhibit iodide uptake by erythrocytes since the levels of nonorganified iodine were 1.2-fold increased after AE in rats which did not receive supplementary KI. One more confirmation is a more considerable growth of free I concentrations in thyroids of rats with hypocorticism (120.4-223.9%, Fig. 11) compared to controls (94.8-128.0%) after administration of KI at the same doses. Iodine organification in AE rats was enhanced by 32-86% in rats treated with 3 to 500 daily doses of KI (Fig. 11). TPO activity in AE rats was 29.4% elevated and 2.4, 3.9 and 3.7-fold increased (Table 9) after administration of 3, 100 and 500 KI daily doses.
Control | Daily doses of KI administered to AE animals | |||||
No administration | 1 | 3 | 100 | 500 | ||
TPO, µmol/min×g protein | 173.9±22.5 | 193.8±10.3 | 275.4±77.4 | 387.9±78.4* | 616.5±178.1* | 579.7±120.6* |
Effect of 2-week administration of 1 to 500 daily doses of potassium iodide on TPO activity (µm/min×g tissue) in thyroids of AE rats
Effect of 14-day administration of 1-500 daily doses of KI on the concentrations of total I, protein-bound I and free I in thyroids of AE rats
Effect of 14-day administration of 1 to 500 daily doses of potassium iodide on the concentrations of total T4 and T3 in the blood serum of rats with normal and lowered glucocorticoid statuses
The repeated and single administrations of excess potassium iodide to rats with hypocorticism were characterized by activation of iodide metabolism in the TG, which was followed by development of pronounced hyperthyroidism in AE animals. The blood serum total T4 concentration (Fig. 12) was increased by 52-100% in rats with adrenal deficiency treated with KI for 14 days compared to control animals. The T3 concentration (Fig. 12) reached 145.5-177.5% of the control level.
In this situation, a pronounced disturbance in the regulatory mechanisms of the pituitary-thyroid axis may be observed, which is accompanied by development of hypothyroidism and indicates a permissive (coordinating) role of glucocorticoids in regulation of thyroid homeostasis.
Our findings indicate that regulation of iodide uptake is very closely related to the state of the pituitary-adrenal system. Excess iodine intake under hypocorticism causes development of hyperthyroiditis.
Short-term stress (5-30 min) induced activation of biosynthesis and secretion of thyroid hormones. The most important established regularity of the post-stress period is restoration of the iodine thyroid status due to activation of uptake and organification of iodine as well as a negative correlation between the total thyroid concentration and adrenal corticosterone concentration (r= –0.952, p=0.003), which indicates participation of glucocorticoids in regulation of iodine thyroid homeostasis.
The most pronounced stress-induced changes in iodine metabolism after the treatment by physiological KI doses (3 daily doses) are characterized by:
disturbed kinetics of blood iodine content within 24 h following the KI treatment, which was characterized by accumulation of blood iodine (826%) after 6 hours following the post-stress period;
changed dynamics of thyroid uptake and oxidation of iodine, which caused a decrease in the concentrations of total I and protein-bound I in thyroids of stressed rats after the treatment with 3 daily doses of KI in contrast to the control group which showed elevation of these indices.
It was shown that repeated exposure to short-term psychoemotional stress (for 4 weeks) induced pronounced structural and metabolic changes in the thyroid gland that were characterized by elevated iodine content, as well as a decrease of the extent of its organification and development of oxidative stress.
The lowered glucocorticoid status in rats is characterized by increased blood thyroid hormone concentrations and decreased TPO activity (44.2%). In contrast to the animals with normal glucocorticoid status, the AE rats did not show any inhibitory effect of high iodine doses (Wolff-Chaikoff’s effect) after the single administration of 1000 daily doses of KI, and activation of thyroid iodide uptake and organification was observed.
The 2-week administration of KI (1-500 daily doses) to rats with glucocorticoid deficiency increased the levels of free iodine (120-224%) and protein-bound iodine (32-86%) as well as thyroid TPO activity. In contrast to controls, this was followed by development of pronounced hyperthyroiditis (T4 amounts to 152-200% and T3 – 145 to 177% of the control values), which is a consequence of impairments in the key mechanisms of thyrocyte regulation and shows a permissive (coordinating) role of glucocorticoids in respect to the given effects.
The state of chronic stress may be a cause of impaired iodine metabolism in thyroid cells, which can induce development of hypothyroiditis and autoimmune thyroid pathology. Deficiency of the pituitary-adrenal system enhances the probability of development of hyperthyroiditis.
AcknowledgementWe are grateful to her colleagues and post –graduate students at the Institute of Pharmacology and Biochemistry of the National Academy of Sciences of Belarus, Dr. Sergey Chumachenko (Ph.D. in Biology), Dr. Sergey Lupachik (Ph.D. in Biology), Ms. Daria Goreva and Ludmila Kiryukhina for the assistance in the implementation of this project.
Search and rescue (SAR) problems for collaborative multi-robot systems (MRS) have been an interesting research topic for several decades [1, 2, 3]. The attractiveness of the domain stems from the variety of problems it incorporates, including mapping and situational awareness, monitoring and surveillance, establishing communication networks, or cooperative decision making. All these aspects make SAR a very difficult problem to solve. Despite the considerable difficulties, conducting SAR operations with autonomous MRS offers many advantages. A capable robotic search and rescue team can replace humans as first responders in disaster areas, map and inspect the site, and make it safe for the approach of human rescue teams.
To facilitate and accelerate progress in the field of search and rescue, many robotics competitions have been held over the years. In recent years, many of them have begun to incorporate multi-domain challenges involving robots from different domains, including aerial, ground, and underwater robots. At the forefront of this concept is the euRathlon [4], the world’s first multi-domain (air, land and sea) multi-robot SAR competition. In a recreated disaster scenario inspired by the 2011 Fukushima nuclear power plant accident, the euRathlon 2015 Grand Challenge required teams of robots to work together to map the area, find missing workers and contain a leak. As a continuation of this initiative, a series of the European Robotics League Emergency Robots [5] (ERL-ER) was organized as part of the European Robotics League. Some changes were made to increase the level and difficulty of the challenges, including more complex manipulation tasks and even more collaboration between robots from different domains. Three ERL-ER competitions were held: Piombino 2017, Seville 2019 and La Spezia 2019.
In parallel, there is another branch of multi-domain competitions that gathers many teams worldwide, the Mohamed Bin Zayed International Robotics Challenge [6] (MBZIRC). MBZIRC focuses not only on SAR missions, but also on promoting the state of the art in robotics in general. The missions are very challenging from both control and algorithmic perspective. They often involve complex manipulation tasks, the need for rapid response and tracking of fast-moving objects, and SAR segments such as fire detection and extinguishing. This competition took place in 2017 and 2020 in Abu Dhabi.
In this chapter, we focus on our efforts in developing an autonomous aerial-ground search and rescue team during the last few years. Our system was formed in two robotics competitions, ERL-ER 2019 Local Tournament in Seville and MBZIRC 2020. In the first competition, we succeeded in setting up the autonomous system for search and rescue missions, including mapping the area and detecting objects of interest. The MBZIRC challenge involved a more complex scenario with three different missions, and we adapted and improved the developed system based on the results of the ERL competition. In this chapter, we detail the hardware and software design and the methodology used to solve the problems in the challenges. At the end of the chapter, we offer important conclusions and practical advice from the years of development of our robotic team to further advance the practical application of autonomous MRS to these types of problems.
The chapter is organized as follows. The next section surveys the state of the art in SAR problems for multi-robot collaborative systems. Section 3 describes the mechanical design of the robotic aerial and ground platforms. Section 4 details the software design for both platforms, including the modules used and the organization of the overall software architecture. Section 5 provides insight into the development of autonomous exploration and mapping of unknown areas using an Unmanned Aerial Vehicle (UAV) or Unmanned Ground Vehicle (UGV) with a LiDAR. In Section 6 we give an insight into the object detection methods we have developed for the ERL and MBZIRC competitions. In Section 7 we analyze the performance of the described system and its components during the competition runs, followed by conclusions and lessons learned as the last section.
Robotics research in the field of SAR has, to a large degree, been driven by competitions and challenges, first of which were introduced in late 90s [7], followed by later establishment of euRathlon [4], DARPA challenge [8], ERL Emergency [5] and MBZIRC [6].
Through the fundamental research in the field of robotics that is required to meet the demanding scenarios, the competitions and challenges are also driving the development of standardized benchmarks for SAR robots, with the US National Institute of Standards and Technology (NIST) leading the way [9]. NIST recognizes the urban search and rescue scenarios as a great tool to measure how intelligent autonomous robots are by looking at several components of an autonomous search and rescue robot or robot team.
The first component of a SAR system is the ability to traverse difficult terrain, which is usually solved by using a heterogeneous robotics team consisting of several robots with different capabilities. For the land-based SAR, there are various formations that are used, such as physically interacting UGV-UGV teams [10] where one robot can carry the other one, physically interacting UAV-UGV teams [11] where the UAV can carry the UGV over obstacles and the UGV can carry the UAV to save energy, or teams where only information is shared [12]. In our work for ERL and MBZIRC, we focus on the information sharing team consisting of a UGV and at least one UAV.
To traverse the terrain and find objects or people, the SAR robotic team needs to be able to perceive the surroundings. While some applications may require acoustic and thermal sensing, our robotic team is equipped with 2D and 3D LiDARs for mapping and navigation and cameras (both RGB and RGBD) for detecting and locating people or objects. For some detection tasks, we used deep neural networks [13], while some objects could be recognized solely by color, similar to [14]. 2D and 3D maps of the environment were built using Google Cartographer [15], which was adapted to use information from the GPS and to also serve as a pose sensor for UAV control [16]. The navigation stack for the UGV is based on the TEB planner [17], while the UAVs rely on the TOPP-RA approach [18].
Generating waypoints for navigation planners is an essential aspect of robot team autonomy. In our work, several methods were implemented: (a) waypoint generation using a 2D lawnmover pattern in relatively small areas of known size; (b) Levvy flight 2D waypoint generation for large areas of known size [19]; (c) autonomous 2D [20] and 3D exploration [21] for areas of unknown size. In this work, we briefly discuss our autonomous exploration approach for ERL and MBZIRC competitions, which was later extended to the planner described in [21], based on the exploration tool called 3D-FBET, work of Zhu et al. [22].
The final component of the autonomous SAR system is collaboration between multiple agents, including humans, which is constantly a topic of great interest in SAR challenges and projects [23, 24, 25]. While we have developed a framework for collaboration and coordination in heterogeneous robot teams [11, 26], due to nature of challenges in ERL and MBZIRC, the developed approaches were not deployed in the field.
In this section, we describe the hardware setup of the robotic platforms used for the search and rescue missions in the ERL and MBZIRC competitions. We outline the mechanical structure of the robots and the components installed on board the vehicles to enable the execution of the specified tasks.
For the hardware design of the UAV, we followed the requirements of the challenge specifications. The main purpose of the aerial platform is to autonomously map and explore the disaster area and search for objects of interest. Therefore, we developed a custom hardware configuration to support this purpose, including the use of appropriate sensors for localization and vision-based algorithms. The mechanical design of the UAV was the same for the ERL and MBZIRC search and rescue missions.
The frame of the aerial platform (Figure 1) consists of four arms, a body, and two legs with skis, all made of carbon. The vehicle is equipped with Flame 60A 12S ESCs which are driving T-motor P60 KV170 12S motors with 22-inch carbon propellers. The autopilot used is a Pixhawk 2.0, and the maximum takeoff weight of the vehicle is 12 kg with a 2 kg payload. The UAV is equipped with an Intel NUC i7/16GB computer running Ubuntu 18.04 LTS and ROS Melodic, which processes input from ZED Mini stereo camera, Smartek Vision camera and Velodyne VLP-16 Puck Lite 3D LiDAR. Image processing for the UAV is performed using convolutional neural networks running on Intel Neural Compute Stick 2. All components of the aerial platform are powered by two LiPo 12S 14000mAh batteries, which give the vehicle a flight time of up to 30 minutes. The summary of components on board of UAV is given in Table 1.
Front view of the aerial platform with all sensors and electronic devices on board.
Component | Specifications | Purpose |
---|---|---|
On-board computer | Intel NUC i7-8650U Quad Core 1.9GHz | Main computing unit |
Autopilot | Pixhawk 2.0 | Flight control, sensors (IMU, barometers) |
Computing unit | Intel Neural Compute Stick 2 | Neural network processing |
GPS sensor | Ublox M8P GNSS reciever | Localization, navigation |
LiDAR | Velodyne VLP-16 Puck Lite | Localization, mapping |
Stereo camera | ZED Mini | Perception, object detection |
UAV hardware component summary. The same setup was used in ERL and MBZIRC competitions.
Ardupilot’s Copter firmware is a full-featured, open-source multicopter UAV controller. Copter is capable of handling the full range of flight requirements, from fast FPV racing to smooth aerial photography to fully autonomous complex missions that can be programmed via a range of compatible software ground stations. The entire package is designed to be safe, feature rich and open to custom applications. Copter firmware is loaded onto the Cube Black autopilot, which includes a 32-bit ARM Cortex M4 core processor with a fail-safe 32-bit coprocessor, 256 KB of RAM and 2 MB of flash memory. Integrated into the Cube are a triple redundant intertial measurement unit (IMU) containing accelerometer, gyroscope and magnetometer as well as two barometers, which are isolated and damped.
The carrier board provides an interface for various Pixhawk-compatible peripherals, as well as power for all components of the drone. On the top of the UAV is an external Global Positioning System (GPS) sensor, whose receiver is based on the high-precision Ublox M8P GNSS module. When paired with the external GPS and antenna via a telemetry module, the vehicle’s GPS (Pixhawk) can achieve centimeter-level accuracy. The copter firmware uses an Extended Kalman Filter (EKF) algorithm to estimate the vehicle’s position, velocity, and angular orientation based on gyroscope, accelerometer, compass, GPS, airspeed, and barometric pressure measurements.
The Velodyne VLP-16 Puck Lite features a rotating array of sixteen infrared laser emitter-detector pairs that rotate at 300 to 1200 RPM. Each of the 903 nm lasers is fired 18080 times per second, and distances are measured based on the time of flight for each pulse. The captured distance measurements can be used to create high-quality point clouds. Each LiDAR sweep covers a vertical angle of 30 degrees with a resolution of 2 degrees and any horizontal angle with a resolution of 0.1 degrees to 0.4 degrees, depending on the RPM setting.
The ZED Mini is a stereo camera that provides high-resolution images and accurate ambient depth measurements. It is designed for the most demanding applications, such as autonomous vehicle control, mobile mapping, aerial mapping, security, and surveillance. It is actually a device with two cameras 65 mm (2.56 inches) apart, designed to mimic the human eye.
The on-board computer used in the UAV is an 8th generation Intel NUC with a powerful Intel i7-8650U Quad Core 1.9GHz processor. The computer has an integrated Intel Iris Plus Graphics 640, a 16GB Kingston SODIMM RAM module and a 250GB Kingston A2000 M.2 SSD as storage unit. The required power supply range is 12-19 V. The operating system installed on the on-board computer is Linux Ubuntu 18.04 LTS with the middleware ROS Melodic. Since the on-board computer needs to be embedded in the body of the drone and to save some weight, the outer case is removed and the computer is mounted on the bottom of the UAV.
In ground search and rescue missions, the choice of the ground mobile platform is mostly dictated by the mission and terrain requirements. In our robotic team, a Husky A200 was chosen as a platform suitable for motion in rough terrain. The competition tasks directly dictated the choice of additional hardware components. The complexity of the MBZIRC tasks was significantly higher compared to the ERL competition, and the hardware design was therefore more elaborate, as explained in this section.
The main task of the UGV in the ERL competition was to autonomously locate objects of interest. Our search and rescue platform is shown in Figure 2, with the autonomous navigation sensor setup: a Sick NAV350 LiDAR, an IMU, a GPS receiver, and a real-time kinematic positioning (RTK) unit for higher precision. For reliable detection of obstacles during movement, LiDAR was mounted on top of the vehicle body, near the front end of the vehicle, so that there is no shadowing from other UGV parts. GPS and RTK units were elevated with respect to the vehicle body to avoid potential signal blockage and interference. The task detection requirements allowed the use of the Intel RealSense D-435, a commercially available RGB-D camera, instead of more precise and expensive alternatives. Thanks to recent technological advances, the camera is small enough to be mounted in the front part of the vehicle without interfering with other sensing components, such as LiDAR beams.
Hardware setup of the UGV and its sensors and actuators used in ERL competition.
Another task of the UGV was to provide first aid kits. For this purpose, a simple 1-DOF manipulator was constructed, sufficient for safe transport and easy unloading of the package. As the ERL task required delivery of two kits, two such manipulators were mounted at the front of the vehicle, outside of the camera field of view. The manipulator links were designed and 3D printed from PLA plastic (shown in red in Figure 2) and driven by Dynamixel servo motors.
The UGV design described was quite simple, quick to implement, and task-specific, resulting in successful mission execution. However, in the long run, it became apparent that a more complex solution would be much more beneficial for mission versatility.
In the MBZIRC competition, we chose to design a mobile manipulator platform, and to rely on the dexterity of the arm for execution of more complex tasks, such as repetitive pick and place in the wall construction scenario. Still, each new task requires some adaptation of the manipulator tool. We equipped the vehicle with a lightweight 6-DOF manipulator, a Schunk Powerball LWA-4P. The arm has integrated joint drives, eliminating the need for additional external control units or power converters. The setup of our platform is shown in Figure 3.
Hardware setup of the UGV and its sensors, actuators, and electronic components used in MBZIRC competition.
One of MBZIRC’s challenges was a wall construction task in which the mobile manipulator had to pick up bricks from their stacks and transport them to the wall pattern, where they had to be arranged in a specified order. Again, a custom gripper was developed to magnetically grasp the ferromagnetic plates on the bricks, as shown in Figure 4. The gripper is lightweight, energy efficient and strong enough to lift up to 2 kg. The design is based on ten small electromagnets, and at least six magnets in contact are required to achieve sufficient force to lift the brick. Due to the rigidity of the mobile manipulator, any irregularity or misalignment on the contact surface could reduce the number of magnets in contact. This was solved with passive compliance, with four shock-absorbing rubber balls providing compensation for misalignment greater than
Design of the passively compliant magnetic gripper for UGV brick manipulation tasks in MBZIRC challenge.
In this scenario, the RGB-D camera was used for detection, navigation, and manipulation. It was therefore mounted as an eye-in-hand on the gripper. For navigation, a 3D LiDAR (Robosense RS-LiDAR-16) was used instead of the 2D solution in ERL. As it turned out, mapping with 2D scans in realistic environments can miss some obstacles, such as those on the ground, below the beam. Other hardware modifications included an additional battery pack and cargo baskets for transporting multiple bricks. The summary of the components on board the UGV, during the ERL and MBZIRC competitions, is shown in Table 2.
Component | Specifications | Purpose |
---|---|---|
On-board | Intel NUC i7-8650U | Main computing unit |
Computer | Quad Core 1.9GHz | |
Autopilot | Pixhawk 2.0 | Sensors |
(IMU, RC control) | ||
Manipulator | ERL - two 1-DoF manipulators | Object manipulation |
MBZIRC - SchunkPowerball LWA-4P | ||
GPS sensor | Ublox M8P GNSS reciever | Localization, navigation |
LiDAR | ERL - Sick NAV350 LiDAR | Localization, mapping |
MBZIRC - Robosense RS-LiDAR-16 | ||
RGB-D camera | Intel RealSense D-435 | Perception, object detection |
UGV hardware component summary. The setups used in ERL and MBZIRC competitions.
Having defined the mechanical structure of the robotic platforms, in this section we address the design of the software modules implemented for each robot. Here we define the software that enables basic operations of the vehicles, such as control, localization, navigation, and trajectory planning, while challenge-specific tasks and more complex algorithms are described in the next section.
UAV platforms used for search and rescue missions are equipped with Ardupilot firmware. The firmware communicates with Micro Aerial Vehicle (MAV) messages using the MAVLink protocol. The Robot Operating System (ROS) is used to communicate with the on-board computer and the drone. The components used in the ROS environment are as follows:
HOLD GROUND: the UAV is on the ground and ready to arm and takeoff.
HOLD AIR: the UAV is in the air and ready to receive external commands.
JOY AIR: the UAV is in the air and is controlled by RC.
In Figure 5 we have illustrated the interaction of the above components within the UAV software architecture on a NUC computer. This figure refers to the case where the UAV state machine is in the HOLD AIR state. The pipeline begins with inputs from the LiDAR and IMU that are fed into the Cartographer SLAM algorithm, which creates the map of the environment and locates the vehicle in the map frame. Next, using the Constant Velocity Model, the estimated odometry of the vehicle is calculated and fed to the UAV position controller. Based on the reference generated with the trajectory planner, the controller generates control outputs of the desired vehicle orientation and thrust and sends them to the MavRos. These messages are then forwarded to the lower level UAV controllers implemented in the firmware. If georeferencing is needed, GPS measurements can also be forwarded to the Cartographer.
Layout and the interaction of the UAV software components running on the on-board NUC computer.
The main software modules used for UGV control in the competition search and rescue missions are those for localisation, motion and manipulation:
The Google Cartographer package was used to create a map of the unknown environment and localize the mobile base within it. During the ERL-ER competition, a two-dimensional version of the Cartographer’s SLAM algorithm was used, utilizing 2D laser scan data from the Sick NAV350 LiDAR. This approach results in only detecting obstacles that are aligned with the LiDAR, and thus led to problems with lower obstacles, more specifically the lower part of the obstacles as shown in Figure 14. The approach we took to overcome this issue was solved using a large safety margin around all the detected obstacles. Later, during our work for the MBZIRC competition, we adopted a different approach using Cartographer’s 3D SLAM algorithm, and a 3D LiDAR.
Ground vehicle motion planning was done with the Move Base package. Since this package uses a 2D cost map, the 2D Cartographer map could be used for safe motion planning with obstacle avoidance. However, with the Cartographer’s 3D SLAM, we filtered the 3D submaps based on their height, to obtain a 2D cost map. Points below the lower threshold are filtered out to avoid classifying the ground as an obstacle. Similarly, points that are above the maximum height of the robot are removed as they do not represent a real obstacle for platform navigation. However, ground points that are far away from the robot may be perceived as false-positive obstacles if the ground is not completely flat. This issue was resolved by creating newer submaps, generated using the 30 most recent laser scans.
The navigation during ERL was based on manually defined waypoints, selected in the map by the user. Move Base package would then autonomously perform the path planning with obstacle avoidance. This semi-autonomous planning system was improved for the MBZIRC competition, by implementing a higher-level planning algorithm that generates desired waypoints autonomously.
Thanks to the Husky A200 ability to rotate in place, the most commonly used navigation planner the DWAP, which heavily relies on this capability. However, such motion causes significant vibrations, and the with the addition of the robotic arm for the MBZIRC competition, this problem is further exacerbated due to the increase in the overall mass and heightening of the center of mass position. Therefore, in the MBZIRC competition we switched to the Timed-Elastic Band (TEB) planner [17] for car-like robots, which uses online trajectory optimization to create a plan constrained by the minimum turning radius.
Exploration and mapping of unknown environments is a fundamental task in robotics. It can be used in many different applications such as inspection, surveillance, 3D reconstruction, and search and rescue. Searching for an object of interest in an unknown environment can be formulated as an iterative process consisting of a map update, selection of a next goal, and navigation to that target. The process is complete when the object of interest is found.
Analogously, the search strategy in the exploration of an unknown environment is similar, but with different objectives. In exploration, the main goal is to create a map of the environment, while in search, the focus is on finding the object of interest. Although search is a central task in many search and rescue scenarios, we use an exploration strategy adapted for the search application.
Typical exploration methods are based on frontiers [27] and are used in both 2D and 3D space. In contrast to 2D exploration and mapping strategies, mapping large environments in 3D requires a considerable amount of memory and computational effort.
To create a map of the environment and locate a robot in it, we use a submap-based graph SLAM method Google Cartographer [15]. The map consists of submaps created from a sequence of sensor scans through scan matching, fusion with IMU and odometry. The map is then used for exploration and robot navigation.
In the ERL competition, some of the objectives were to locate missing workers, entrances to the building, and damage to structures while creating a map of the environment. The proposed layout for the ERL competition is an area of approximately 200 m by 30 m with obstacles. Since the ERL arena may contain GNSS -degraded areas, we used a SLAM algorithm for map generation and robot localisation. We adopt Cartographer SLAM to generate a 3D map onboard the robot in real time. Objects of interest are detected during semi-autonomous navigation, where an operator manually selects desired waypoints for the robot to reach autonomously. Both 2D and 3D maps of the environment are generated, and the positions of objects of interest are marked on the map.
In the MBZIRC challenge, we consider autonomous exploration and search of a UAV in an unstructured outdoor environment. In this challenge, we used only one UAV because it can fly over the area quickly and has the advantage of bird’s eye view. The goal is to explore and map the environment while searching for the object of interest (a fire). Initially, the area is unknown, while it is assumed that the boundaries of the area are known. Since the area for exploration and mapping is limited, the exploration is finished when the entire area is covered or when the objects of interest are found.
In order to explore an area, create a map and find the objects of interest, the search strategy is formulated. The search strategy algorithm generates waypoints for trajectory planning considering the boundaries of the environment. In addition, the strategy aims to explore the environment as quickly as possible while trying not to miss the objects of interest.
Waypoints can be generated in a variety of forms. For our scenario, we use the lawnmower pattern with the predefined horizontal and vertical size of an area and with the spacing value indicating how far apart the segments of the trajectory are. The lawnmower pattern is easy to implement and is suitable for exploration and search for the desired object.
The search strategy represents an input to the trajectory planning module, which generates the trajectory from the given waypoints. Objects of interest are detected during robot navigation. An overview of the proposed system is shown in Figure 6. The map provided by Cartographer is reliable and enables successful exploration while searching for fire.
Overall schematic diagram of autonomous exploration and search. The cartographer SLAM creates a map, that is used for the trajectory planning module. The generated trajectory navigates the robot towards the waypoint.
In autonomous exploration, a suitable trajectory planner should be used to navigate the robot to the desired point. After the search algorithm computes the points in the specified arena, they are forwarded as waypoints to a trajectory planner. The robot starts following the planned trajectory and navigates to the next point. At the same time, the algorithm for detecting objects of interest runs in the background. For the safe navigation of the robot, we use the trajectory following solution described in [11].
Another major feature of the SAR systems is the ability to detect various objects of interest. In the ERL, the robots had to detect four different objects – a blocked entrance (blue rectangle), an unblocked entrance (green rectangle), damage to the building (red rectangles), and a missing worker (a dummy wearing a helmet and a safety vest). Some of the aforementioned objects are shown in the ERL arena in Figure 7. In the MBZIRC competition, one of the challenges was to locate and extinguish fires. Although there were variants of fires to be extinguished with water, we focused on the ground fires over which the robots had to throw blankets, as shown in Figure 8.
Objects of interest to be detected in ERL competition. Images display the missing worker mannequin, obstructed entrance (blue rectangle), and damages to the structures (red rectangles).
Ground fires to be found and covered with blankets during MBZIRC competition (Image source:
We used different strategies to detect objects of interest in these two competitions. For the ERL competition, we chose to use visual recognition using a neural network, for which a custom training dataset had to be created, even though the exact object was not known a-priori. To mitigate these issues and simplify the approach, we decided to use a color segmentation algorithm for object detection in the MBZIRC challenge. The simplicity of the objects to be found in this semi-structured challenge and the straightforwardness of the method and its application were the main reasons for this decision. Both methods and their properties are described in the rest of this section.
The ERL search and rescue mission required recognition of several simple markers, and a human figure wearing a helmet and a vest, representing a missing worker. Even though the markers were rectangular and easily distinguished by color, we opted for the deep learning-based approach to detection because of the complexity of human figure recognition. For this reason, we relied on the transfer learning approach, taking advantage of the pre-trained deep convolutional network based on the YOLO architecture. Since we only needed to recognize 4 object classes, but needed this in real-time on constrained computational resources, we opted for the tiny-yolo version of the network (Figure 9).
Detection of the red rectangles using YOLOv3 real time object detection.
For our detection task, we created a small custom training dataset. A large number of images with simple rectangular objects can easily be created in different environments, with the limiting factor in the cost of manual labeling procedure. For the case of a mannequin representing the missing worker, the difficulty was in not knowing exactly what this object would look like. The final dataset consisted of around 150 images, out of which around 50 contained the human figure various poses and cluttered environments, and around 100 contained the rectangular markers.
Finally, we trained the network using DarkNet implementation, with the following parameters:
The detection tasks in the MBZIRC competition were simpler compared to ERL, allowing for solution based on color segmentation. Hence, the fire detection in the third challenge of the MBZIRC competition was performed using color-based image filtering (Figure 15). The image received from the camera is filtered using pre-tuned Hue-Saturation-Value (HSV) thresholds. Contour detection is then performed on the filtered image, and contours with areas below a lower threshold are disregarded. If multiple contours remain, the one with the largest area is selected as the detected fire. The center of the contour is used as its position for the visual servoing procedure.
Although this chapter focuses on SAR applications of MRS, one of the challenges during the MBZIRC competition was to achieve a more precise object manipulation in the wall building scenario that could be easily applied to the search and rescue domain. Our proposed solution involved precise 3D object detection that can be applied to other objects that need to be handled during emergency operations.
In the competition, the robots had to autonomously manipulate brick-shaped objects to build a wall. A ferromagnetic patch was attached to the top of the bricks for grasping. At the beginning of the challenge, the bricks were arranged as structured stacks, separated by color.
Initially, stacks of different colors are detected using a method similar to that used for fire detection, with different HSV thresholds used for red, green, blue and orange brick stacks. To distinguish individual bricks, ferromagnetic patches are detected within the convex hull of a detected brick stack. Contours resembling a rectangle are selected as candidate objects. To select a single brick for manipulation, a scoring scheme is used to calculate the desirability of each candidate. The desirability is calculated based on the area and image position of the candidate contour:
where
Our approach to determining the real-world pose of the detected magnetic patch, was to use an inverse of the Perspective-N-Point problem [28]. Assuming that the ferromagnetic patch is parallel to the ground, the positions of the endpoints of the detected rectangle in the image can be transformed into real positions using:
Real-world camera position - from localization and manipulator kinematics.
Height of the ferromagnetic patch - from the organized pointcloud obtained from the RealSense camera.
Known width of the ferromagnetic patch.
Camera calibration parameters.
In this section, we present the results obtained during the challenge runs in the two robotics competitions. We analyze the performance of our robotic team in the autonomous mapping and exploration and object detection tasks.
Looking from the lens of the robotic competitions, we first present the results of the proposed UAV-UGV team in the competition arena. Here we provide challenge descriptions, and the scores obtained during the trials in the ERL-ER and MBZIRC.
The target scenario of ERL-ER is emergency response in an industrial environment affected by an earthquake. The UAV-UGV team serves as a first responder in this disaster-stricken area to secure the perimeter and enable the arrival of human rescue teams. The robots must search for two missing workers, find them as quickly as possible, and provide both with an emergency kit. The robots must also check the condition of the building after the earthquake. To do this, they output a detailed map of the surroundings to assess the safety of the area.
The competition took place in an outdoor arena of approximately
At the tournament in Seville, five teams competed in a four-day competition. As specified in the rules of the competition, each team’s final score was determined as the median value of all four attempts. Table 3 shows the full results of all teams and their attempts, as well as the final score. At the expense of a lower score, we aimed for full autonomy during all trials. Therefore, the UAV, which was in an earlier stage of development, did not perform as well. However, the UGV did great, and we were able to use it to test the SLAM algorithm, as well as object detection. This tournament proved to be an excellent development and testing ground for the upcoming MBZIRC competition.
Wed, Feb 20 | Thu, Feb 21 | Fri, Feb 22 | Sat, Feb 23 | ||||||
---|---|---|---|---|---|---|---|---|---|
TEAM | A | PB | A | PB | A | PB | A | PB | median |
Raptors | 0 | 0 | 16 | 0 | 20 | 0 | 27 | 3 | 18 |
ENSTA Bretagne | 0 | 0 | 9 | 1 | 17 | 1 | 25 | 2 | 13 |
KAUST | 0 | 0 | 8 | 1 | 11 | 1 | 18 | 0 | 9.5 |
ENSTA Paris | 0 | 0 | 9 | 2 | 0 | 1 | 19 | 1 | 4.5 |
Team results by day and the total score (median) for the ERL-RL Seville 2019 competition [29]. Column A represents team scores, PB penalized behaviors, while attempts marked with
Other teams took the manual approach, such as teleoperation. For example, the user interface of Raptors was built in LabVIEW and the communication layer is based on the ROS software [30]. The system they developed supports the operator during teleoperation and during partial autonomy of the robots.
The MBZIRC competition involved three different challenges – tracking and capturing a target, building a wall, and disaster response in a fire scenario. Here we focus only on the latter, as it falls within the scope of SAR missions.
Challenge 3 of MBZIRC comprised a team of UAVs and a UGV working together to autonomously extinguish a series of simulated fires in an urban high-rise firefighting scenario. The arena, measuring
Our strategy for the challenge was to primarily focus on the ground fires, because they required minimal changes to the robot design. Therefore, we attempted to detect and extinguish the outdoor fires using a fire blanket deployed by the UAV. During the two trials, we managed to partially cover one of the two existing ground fires. This attempt was enough to place us in seventh place out of 20 participating teams. Although seemingly simple, the task proved very challenging for many teams, as shown by the results presented in Table 4.
TEAM | Score | Time left | Rank |
---|---|---|---|
University of Seville, Tecnico Lisboa (IST Lisbon), CATEC | 12.2625 | 0 | 1 |
Technical University of Denmark | 10 | 0 | 2 |
University of New South Wales Sydney | 10 | 0 | 2 |
Czech Technical University in Prague, University of Pennsylvania, NYU | 7 | 0 | 4 |
Korea Advanced Institute of Science and Technology (KAIST) | 7 | 0 | 4 |
University of Tokyo | 5 | 120 | 6 |
Polytechnic University of Madrid, University Pablo Olavide, Poznan University of Technology | 5 | 0 | 7 |
Virginia Tech | 4.5 | 0 | 9 |
The results of the best 9 out of 20 participating teams in the MBZIRC 2020 competition. These results were obtained in fully autonomous mode and therefore rank above manual approaches. The full results are available at [31].
An approach similar to ours was used by a team consisting Polytechnical University of Madrid, University Pablo Olavide and Poznan University of Technology [32]. In their localization, they also used a map-based approach and used 3D LiDAR scans in LOAM: Lidar Odometry and Mapping algorithm. A different approach was taken by the team from Czech Technical University in Prague, University of Pennsylvania and NYU [33] who used Global Navigation Satellite System (GNSS) for outdoor localization and a 2D LiDAR and stereo camera for indoor localization. For fire detection, both teams decided to use infrared cameras to detect heat sources. In the case of wall fires, this was a logical solution. Since we were not targeting these fires, our image-based detection worked just as well for the red floor fires. These results demonstrate the difficulty of SAR applications in real-world conditions in outdoor arenas and the potential for great progress in this area of research.
In the field of autonomous mapping and exploration, we can observe an evolution of approaches. In the ERL competition, we explored the area manually (using an RC controller) or semi-autonomously (generating waypoints in the graphical interface and reaching them autonomously). For the MBZIRC challenge, we extended the method to autonomous exploration, where the robots could search the area and expand the map based on the autonomous exploration algorithm described in Section 5.
The maps created during the ERL competition with UGV are shown in Figure 10, and 2D and 3D UAV maps are shown in Figure 11. In both the 2D and 3D maps, we see high-resolution detailed maps of the competition arena. Here, we demonstrate the ability of the proposed system to generate accurate maps during the mission runtime. However, in MBZIRC, we have gone a step further and combined the map generation with the autonomous waypoint selection method. The result of the obtained map can be seen in Figure 12.
2D map built by UGV during an ERL competition run.
2D (left) and 3D (right) map of the outdoor and indoor area of ERL arena generated by the UAV.
Side view (left) and top view (right) of the 3D map of the outdoor MBZIRC area created with the UAV.
The complete trajectory performed by an UAV is shown in Figure 13. The trajectory is obtained during the first experiment where we used manual navigation. The drift after loop closure was less than 0.3 m. We can conclude that Cartographer SLAM is useful when we navigate in the map and when we have a closed loop with trajectory planning and navigation. A more detailed analysis of Cartographer performance can be found in [16].
A trajectory performed by an UAV in the MBZIRC challenge.
It can be observed that the accuracy of the final maps is not perfect compared to the mobile mapping technologies. This is due to the use of Cartographer SLAM, as it requires a feature-rich environment, a well-sampled IMU and loop closure to generate as accurate map as possible. In [16], it is shown that Cartographer accumulates more drift than other state-of-the-art strategies, but Cartographer can detect loop closure independently and the drift can be corrected. In other words, Cartographer accumulates a significant amount of drift (up to 2 meters), but upon returning near the start position, this drift is corrected (up to 0.2 meters) by closing the loop through the global SLAM.
In addition, closing the loop allows the correction of the cumulative drift, which provides higher pose and map accuracy during the flights. Due to the specific tasks performed in the challenges, closing the loop is not guaranteed to provide an accurate map. Future work will include significant efforts to improve map accuracy so that the map can be used not only in autonomous search and exploration tasks, but also in tasks that require a more accurate map, such as autonomous wall building, obstacle avoidance, and building inspection.
Next, we analyze the performance of the two object detection methods described in Section 6. In Figure 14 we show several examples of detection of objects of interest by UGV using the algorithm described in 6 for ERL competition. These images were taken by a UGV on-board camera during several mission runs. The positions of the first three detected objects match those on the UGV map in Figure 10. We were able to detect the majority of the searched objects during the mission run. This mainly refers to the rectangular objects indicating blocked and unblocked entrances as well as damage to the building. However, due to the specifics of the missing worker mannequin, our neural network training set did not include the exact figure in any of the images. Therefore, we had difficulty performing this detection. This could be mitigated by training the network with a dataset containing a more accurate representation of the object being searched for, or by using a different approach. For example, color-based image segmentation might be appropriate since the safety vest has a very distinct orange color.
Image frames showing detections of objects of interest during ERL competition runs of the UGV.
The output of the color-based fire detection algorithm in the MBZIRC competition is shown in Figure 15. The left side shows the original image, while the right side shows the image masked based on the predefined HSV threshold values. The green outline represents the object contour, while the yellow circle in the center represents the center of the object in the image. This approach provides a fast and efficient method for detecting simple objects of interest, which is certainly the case with a bright red fire. However, some care must be taken when setting the HSV thresholds, as the image colors are dependent on the illumination properties, which can change depending on outdoor lighting conditions.
Fire detection for the third MBZIRC challenge.
This chapter presented the development of an autonomous aerial-ground search and rescue robotic team at the University of Zagreb, driven mainly by two large competitions: European Robotics League and Mohamed Bin Zayed International Robotics Challenge.
The hardware aspect of the robot team is developed considering specific requirements of the challenges, with the challenge-specific design decisions being more pronounced in our UGV design, ranging from simple 1DOF ejector arms to 6DOF mobile manipulator. On the other hand, our aerial platform did not require major hardware changes, as challenges did not require the UAV to interact with the environment on a similar scale to UGVs, but the trend is clearly changing and it can be expected that future challenges will require more and more interaction with the environment from the UAVs.
The biggest lesson to be learned from competition driven development, as evidenced by the software stack described in this chapter, is to design a modular system, both on the level of a single robot (interchangeable sensors and actuators that can easily be plugged into the existing control structure) but also on the level of a team. The modularity of our SAR robotic team is shown in using different sensors and algorithms for UGV mapping and navigation, and easily extending exploration strategies for the UAV.
Given the current state of our system, and the competitions being expected to become more and more challenging, the navigation through the unknown difficult environment is of utmost priority, which will require semantic segmentation of built 3D maps to differentiate traversable terrain from obstacles, both for the UGV and UAV. With the use of UAVs in SAR going from large open spaces to more confined urban areas, it is necessary to further develop the mapping and localization algorithms to provide a stable localization feedback for control and trajectory execution of UAVs in obstacle-rich environments.
This work has been supported by European Commission Horizon 2020 Programme through project under G. A. number 810321, named Twinning coordination action for spreading excellence in Aerial Robotics - AeRoTwin and by the Mohammed Bin Zayed International Robotics Challenge. The work of doctoral students Barbara Arbanas (DOK-2018-01), Ana Batinović (DOK-2018-09), Marko Car (DOK-2015-10), and Marsela Polić (DOK-2018-09) has been supported in part by the “Young researchers’ career development project–training of doctoral students” of the Croatian Science Foundation. DOK-2018-01 is financed by the European Union from the European Social Fund.
ERL | European Robotics League |
MBZIRC | Mohamed Bin Zayed International Robotics Challenge |
UAV | Unmanned Aerial Vehicle |
UGV | Unmanned Ground Vehicle |
SAR | Search and Rescue |
MRS | Multi-Robot Systems |
RTK | Real-Time Kinematic positioning |
TOPP-RA | Time-Optimal Path Parametrization by Reachability Analysis |
SLAM | Simultaneous Localization and Mapping |
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Some possible remedies are suggested, which should include incorporating the value of the principal residence within the assets test. The chapter therefore illustrates the application of principled analysis to policy issues of this sort.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Anthony Asher and John De Ravin",authors:null},{id:"72847",doi:"10.5772/intechopen.93250",title:"Lifestyles, Health, and Life Satisfaction among the Portuguese Seniors",slug:"lifestyles-health-and-life-satisfaction-among-the-portuguese-seniors",totalDownloads:461,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter focuses on the interaction between lifestyles, health, and life satisfaction of Portuguese seniors. The aim of the analysis is to find the main determinants of health and life satisfaction and to verify the importance of lifestyle variables as determinants of health and life satisfaction. We used data collected by the National Health Survey of 2014 and estimated two ordered probits. The main results show that not all lifestyle variables are meaningful in explaining self-assessed health and life satisfaction. The determinants of the health status include education and income; however, it can be assumed that overall good health, family, or close people and income contribute to life satisfaction. A general profile of the Portuguese seniors is provided; however, the results obtained here are changing as a new scenario is emerging, generation X enters old age.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Aida Isabel Tavares",authors:[{id:"196819",title:"Prof.",name:"Aida Isabel",middleName:null,surname:"Tavares",slug:"aida-isabel-tavares",fullName:"Aida Isabel Tavares"}]},{id:"73975",doi:"10.5772/intechopen.94281",title:"Retired but Not Tired: Entrepreneurial Motives and Performance among Retired Public Servants in Tanzania",slug:"retired-but-not-tired-entrepreneurial-motives-and-performance-among-retired-public-servants-in-tanza",totalDownloads:419,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Venturing into a business venture at an old age is an interesting phenomenon. Retirees seem to consider this decision as imperative as it provides them with a source of earning and keeps them active post-retirement. Despite a plethora of research on entrepreneurship, there is a paucity of research on entrepreneurial behavior and performance retired public servants. The current study examines the motive and performance of businesses owned by retired public servants in Tanzania, one of the developing economies. The study used a survey of 90 randomly selected public servants who retired between 2012 and 2016. The descriptive and probit regression analyses were used to examine the entrepreneurial performance and factors associated with it. The results of the analysis suggest that the performance of the businesses is generally not good, as the majority made losses for the past 3 years consecutively. As for the determinants of performance, the study observed that age and source of capital negatively affect performance, whereas education and planning/preparations for business establishment positively influenced entrepreneurial performance. The findings imply that employees, employers and social security industry have a role to play in creating awareness and preparing public service employees for life after retirement especially in sustaining post-retirement income. Lumpsum pension and monthly allowance may be necessary, but the knowledge to manage them through profitable business ventures my be sufficient for a better post-retirement life.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Anselm Namala and Mursali A. Milanzi",authors:null}],mostDownloadedChaptersLast30Days:[{id:"70904",title:"Addressing the Pension Decumulation Phase of Employee Retirement Planning",slug:"addressing-the-pension-decumulation-phase-of-employee-retirement-planning",totalDownloads:642,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Longevity increases and population ageing create challenges for all societal institutions, particularly those providing retirement income, healthcare, and long-term care services. At the individual level, an obvious question is how to ensure all retirees have an adequate, secure, stable, and predictable lifelong income stream that will allow them to maintain a target standard of living for, however, long the individual lives. In this chapter, we review and discuss the main pension decumulation options by explicitly modelling consumers’ behaviour and objectives though an objective function based on utility theory accounting for consumption and bequest motives and different risk preferences. Using a Monte-Carlo simulation approach calibrated to US financial market and mortality data, our results suggest that purchasing a capped participating longevity-linked life annuity at retirement including embedded longevity and financial options that allow the annuity provider to periodically revise annuity payments if observed survivorship and portfolio outcomes deviate from expected (or guaranteed) values at contract initiation deliver superior welfare results when compared with classical annuitization and non-annuitization decumulation strategies.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Jorge Miguel Ventura Bravo",authors:null},{id:"72453",title:"The End of the Retirement “Age”: How the New World of Work Is Transforming the Old World of Retirement",slug:"the-end-of-the-retirement-age-how-the-new-world-of-work-is-transforming-the-old-world-of-retirement",totalDownloads:635,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The nature of work is undergoing fundamental transformation in the twenty-first century with drivers including digitalization, automation, and new forms of work organization. This chapter explores how the concept of retirement itself is increasingly redundant in relation to the new world of work. Of course, working lives inevitably do come to an end, but for whom, and at what point, and under what personal and social financial conditions, is this end point? Many people will want, and be required by public policy, to continue their working lives well into later life. In addition, the new dynamics of work and employment unfolding may enable this later life engagement. But in the “post-work” world predicted by many scholars, will later life employment be a possibility for them, and even for many people in their middle and younger years? This chapter explores the implications of the future of work for how traditional models of working lives and retirement need to be restructured and examines the one vital reform to ensure everyone can sustain a decent life in the new highly volatile world of work.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Veronica Sheen",authors:null},{id:"71893",title:"Alternatives to Serve the Interests of Russian Pensioners",slug:"alternatives-to-serve-the-interests-of-russian-pensioners",totalDownloads:433,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The results of the analysis of statistical data on the Russian labor market, employment and wages, as well as the specific features of the Russian pension system, provide the basis for several important conclusions. Firstly, the living standards of the majority of Russian pensioners do not meet their needs as the Russian pension system is focused on the achievement of minimum living standards. Secondly, the regulation on the functioning of the pension system established by Russian legislation is often violated by the regulators without coordination with economic entities and citizens, participants of the pension system, which prevents future pensioners from feeling protected upon retirement. For this reason, citizens of the retirement age do not seek to retire even when they reach the retirement age. The growth rate of working pensioners (who pay taxes, including insurance deductions to the Pension Fund of Russia and private pension funds) confirms this. Thirdly, there is a need to create a socially-comfortable environment for pensioners, to counteract the psychological problems of older people their sense of “uselessness” to society. The article proposes practical measures to mitigate the negative phenomena in the pension provision of Russian citizens.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Elena Ivanovna Kulikova",authors:null},{id:"71593",title:"Called to Plan: Changing Patterns and Perceptions of Retirement for Australian and New Zealand Faith-Based Ministers",slug:"called-to-plan-changing-patterns-and-perceptions-of-retirement-for-australian-and-new-zealand-faith-",totalDownloads:543,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The rising tide of aging citizens globally suggests a compelling argument for increasing understanding of factors impacting retirement. Factors such as health and finance have been identified as principal, but these results generally apply to homogenous groups with little reference to the impact of culture and tradition. This study adopted an ex post-facto, cross-sectional, self-reporting survey from working faith-based ministers in Australia and New Zealand to ascertain personal and professional factors affecting retirement perception in specific context including results for age-related differences. Results from four areas of foci show participants generally regarded retirement as a positive season. They were, however, less confident about their preparedness and mostly dissatisfied with the level of planning for retirement. Significant differences were noted in age-related groups with health and financial considerations constituting the primary differences. Increased understanding of changing patterns and perceptions for specific groups including age differences, potentially aids the response of state and society to the ageing phenomenon.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Bernadene Erasmus and Peter John Morey",authors:null},{id:"71712",title:"The Age Pension Means Tests: Contorting Australian Retirement",slug:"the-age-pension-means-tests-contorting-australian-retirement",totalDownloads:585,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Most Australian retirees are likely to be subject to the Age Pension assets or income test at some point. Evidence is that many retirees adapt their consumption to increase Age Pension entitlements, but long-term implications are difficult to determine—even if the current rules were to remain in place. This chapter evaluates the current approach to means testing against the principles set out in a Department of Social Services discussion paper on this topic. We evaluate the implied “effective marginal tax rates” (EMTRs) on the assets of part pensioners who are subject to the assets test. We find that depending on a variety of parameters such as assumed future earnings rates, demographic status, drawdown strategy and the base level of assets held, the EMTRs are high enough to explain material distortions to savings decisions of those still in employment, and the spending and investment decisions of retirees. Optimal decisions in this context require contorted retirement strategies that do not appear to be in anyone’s interest. Some possible remedies are suggested, which should include incorporating the value of the principal residence within the assets test. The chapter therefore illustrates the application of principled analysis to policy issues of this sort.",book:{id:"8090",slug:"who-wants-to-retire-and-who-can-afford-to-retire-",title:"Who Wants to Retire and Who Can Afford to Retire?",fullTitle:"Who Wants to Retire and Who Can Afford to Retire?"},signatures:"Anthony Asher and John De Ravin",authors:null}],onlineFirstChaptersFilter:{topicId:"1337",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. 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Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Plant Physiology",value:13,count:1},{group:"subseries",caption:"Human Physiology",value:12,count:2},{group:"subseries",caption:"Cell Physiology",value:11,count:8}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:1},{group:"publicationYear",caption:"2020",value:2020,count:4},{group:"publicationYear",caption:"2019",value:2019,count:5},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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