*5.1.1 History and examination*

Extensive history should be taken in all patients with goiter (**Table 2**).

Following points should be highlighted while taking history like place of residence (patients from high altitude areas iodine deficient), dietary iodine intake, family history of thyroid disorders, radiation exposure and any history of goitrogenic drugs intake.

#### **Table 2.**

*Differential diagnosis of swelling in anterior aspect of neck.*

Major concern of nodular thyroid disorder is development of malignancy. Hence history regarding risk factors for malignancy like age (<20 and >60 years), male sex, previous radiation exposure, family history of thyroid malignancy, MEN 2A syndrome should be obtained.

#### **5.2 Clinical evaluation**

#### *5.2.1 Physical examination*

The thyroid examination is done with patient in sitting or standing position. Goiter is classified according to World Health Organization (WHO) classification [11] (**Table 3**).

Thyroid gland is palpated from behind the patient with neck relaxed and looked for size, consistency, nodules, and tenderness and lymphadenopathy.

Consistency of the enlarged gland helps in making diagnosis. Lesions which are hard for palpation suggest malignancy but rarely Reidel's thyroiditis may present like this. The gland feels rubbery in Hashimoto's thyroiditis. Diffuse tenderness can be elicited in sub-acute Thyroiditis.

Palpable thrill and hearing of bruit during auscultation over the gland suggest hypervacularity, it is seen in condition like Graves' disease.

During local examination one should look for lymphadenopathy and following group of lymph nodes should be examined (1) supraclavicular nodes, (2) anterior cervical chain lymph nodes, (3) posterior cervical chain lymph nodes, and (4) submental lymph nodes.

#### *<IP_ADDRESS> Pemberton's maneuver*

The patient is advised to rise both the arm till they touch the face on respective sides. The test is considered positive if patient develops facial plethora. Thyroid gland obstructing thoracic inlet which lead to venous obstruction is considered to be the underlying mechanism.

**Table 3.** *WHO classification of goiter.*

**9**

*Goiter: Overview of Aetiopathogenesis and Therapy DOI: http://dx.doi.org/10.5772/intechopen.90028*

General • Lethargy • Somnolence • Weight gain • Cold Intolerance Cardiovascular • Bradycardia • Angina

**Table 5.**

**Tables 4** and **5** respectively.

*Signs and symptoms of hypothyroidism.*

• Congestive heart failure • Pericardial Effusion Hematological • Anemia

*5.2.2 Investigation*

*<IP_ADDRESS> Thyroid function test*

*<IP_ADDRESS> Thyroid peroxidase antibodies*

*<IP_ADDRESS> Thyroid ultrasound*

General examination includes looking signs of hyperthyroidism, hypothyroidism

Symptoms of thyroid malignancy: Most commonly manifest as solitary nodule which are usually painless in nature. Malignant conversion of thyroid nodules is more common among males than females. Hoarseness of voice and dysphagia sug-

Malignant nodules on palpation range from soft to hard consistency. Regional

Thyroid function test is evaluated starting with measurement of measurement of serum TSH level. If TSH level are less than normal values then next step is to measure T3 and. Normal T3 and T4 level (total T4: 4.5–12.5 μg/dL, free T4: 0.8–1.7 ng/dL, total T3:0.8–2.0 ng/ml, free T3: 2.3–4.2 pg./mL) suggest subclinical hyperthyroidism whereas elevated T3 and T4 level suggest overt hyperthyroidism. Both overt and subclinical hyperthyroidism suggest Graves' disease or toxic MNG. If TSH levels are less than normal value then next step is to measure T4 level. Subclinical hypothyroidism is considered when value of TSH levels between 5 and 10 *μ*U/ml with normal T4 level. Iodine deficiency and Hashimoto's thyroiditis are

Presence of the antibody in serum suggest autoimmune thyroid disorder

Even though all patients with enlarged thyroid gland requires sonographic assessment to rule out malignancy, risk decreases in patients having TSH below normal or in low normal range. There are certain indications which make ultrasound assessment

and metastatic involvement of different organs in suspected thyroid malignancy. Signs and symptoms of hyperthyroidism and hypothyroidism are enlisted in

Reproductive system

• Infertility • Menorrhagia

Dermatological • Dry flaky skin and hair

Neuromuscular • Aches and pains • Muscle stiffness • Carpel tunnel syndrome

• Hoarseness • Cerebellar ataxia

• Myotonia • Depression • Psychosis

• Delayed deep tendon reflex

• Myxedema • Malar flushes • Vitiligo • Carotenemia Gastro-intestinal • Constipation • Ileus • Ascites

gest local involvement of recurrent laryngeal nerve and digestive tract.

the most common cause of subclinical or overt hypothyroidism.

lymphadenopathy suggests lymph node metastasis.

Grade 0: No goiter is palpable or visible.

Major concern of nodular thyroid disorder is development of malignancy. Hence history regarding risk factors for malignancy like age (<20 and >60 years), male sex, previous radiation exposure, family history of thyroid malignancy, MEN 2A

The thyroid examination is done with patient in sitting or standing position. Goiter is classified according to World Health Organization (WHO) classification

for size, consistency, nodules, and tenderness and lymphadenopathy.

hypervacularity, it is seen in condition like Graves' disease.

Grade 1: Palpable goiter, not visible when neck is held in normal position

**Increased sweating Onycholysis** Hyperpigmentation Thinning of the hair Systolic hypertension Increase appetite Weight loss Palpitation Heat intolerance Insomnia

Eye: lid retraction, lid lag, exophthalmos, ophthalmoplegia

*Symptoms and signs of hyperthyroidism.*

Thyroid gland is palpated from behind the patient with neck relaxed and looked

Consistency of the enlarged gland helps in making diagnosis. Lesions which are hard for palpation suggest malignancy but rarely Reidel's thyroiditis may present like this. The gland feels rubbery in Hashimoto's thyroiditis. Diffuse tenderness can

Palpable thrill and hearing of bruit during auscultation over the gland suggest

During local examination one should look for lymphadenopathy and following group of lymph nodes should be examined (1) supraclavicular nodes, (2) anterior cervical chain lymph nodes, (3) posterior cervical chain lymph nodes, and (4) sub-

The patient is advised to rise both the arm till they touch the face on respective sides. The test is considered positive if patient develops facial plethora. Thyroid gland obstructing thoracic inlet which lead to venous obstruction is considered to

Grade 2: A clearly swollen neck (also visible in normal position of the neck) that is consistent with a goiter on

Hyper defecation Menstrual irregularity oligo-/hypomenorrhea

**8**

**Table 4.**

*Signs and symptoms of hypothyroidism.*

General examination includes looking signs of hyperthyroidism, hypothyroidism and metastatic involvement of different organs in suspected thyroid malignancy.

Signs and symptoms of hyperthyroidism and hypothyroidism are enlisted in **Tables 4** and **5** respectively.

Symptoms of thyroid malignancy: Most commonly manifest as solitary nodule which are usually painless in nature. Malignant conversion of thyroid nodules is more common among males than females. Hoarseness of voice and dysphagia suggest local involvement of recurrent laryngeal nerve and digestive tract.

Malignant nodules on palpation range from soft to hard consistency. Regional lymphadenopathy suggests lymph node metastasis.

#### *5.2.2 Investigation*

#### *<IP_ADDRESS> Thyroid function test*

Thyroid function test is evaluated starting with measurement of measurement of serum TSH level. If TSH level are less than normal values then next step is to measure T3 and. Normal T3 and T4 level (total T4: 4.5–12.5 μg/dL, free T4: 0.8–1.7 ng/dL, total T3:0.8–2.0 ng/ml, free T3: 2.3–4.2 pg./mL) suggest subclinical hyperthyroidism whereas elevated T3 and T4 level suggest overt hyperthyroidism. Both overt and subclinical hyperthyroidism suggest Graves' disease or toxic MNG.

If TSH levels are less than normal value then next step is to measure T4 level. Subclinical hypothyroidism is considered when value of TSH levels between 5 and 10 *μ*U/ml with normal T4 level. Iodine deficiency and Hashimoto's thyroiditis are the most common cause of subclinical or overt hypothyroidism.

#### *<IP_ADDRESS> Thyroid peroxidase antibodies*

Presence of the antibody in serum suggest autoimmune thyroid disorder

#### *<IP_ADDRESS> Thyroid ultrasound*

Even though all patients with enlarged thyroid gland requires sonographic assessment to rule out malignancy, risk decreases in patients having TSH below normal or in low normal range. There are certain indications which make ultrasound assessment mandatory like palpable solitary nodule, palpable multinodular goiter, and suspicion of nodule in patient with difficult neck palpation, rapid growth of a goiter, thyroid asymmetry, firm consistency, tenderness, normal TSH and negative TPO antibodies.

### *<IP_ADDRESS> Fine-needle aspiration cytology*

Indications for FNAC include rapid growth of the swelling which suggest malignant transformation, signs of inflammation (abscess formation) and nodules with indeterminate or suspicious features (ultrasound proven).

### *<IP_ADDRESS> Computed tomography of neck*

Computed tomography of neck not usually advised is required rarely to assess the extension of large cervical goiters and sub sternal goiters.


**4.6 Other organs**

In the tongue, nodular deposition is seen, causing macroglossia. Gastrointestinal tract deposition of amyloid is common with polyps or ulcerative lesions. In the late stage, the cut surface shows yellow and waxy mural thickening. Clinically, it can cause motility disorders or stricture. Not uncommonly, vessels in the gastrointestinal tract can have amyloid deposition. In the respiratory tract, grossly nodular appearance is seen, and histologically, such depositions can be divided into four patterns including tracheobronchial, nodular parenchymal, diffuse alveolar septal, and lymphatic [11]. Skin depositions vary in size and shape, from papules to nodules and plaque. As an endocrine organ, the thyroid can present with goiter and is associated with medullary carcinoma. Localized nodular deposition in the bone causes amyloidoma. Inflammation including giant cell, lymphocyte, and spheroid structure has been reported [12]. Joint depositions are seen mimicking rheumatoid arthritis, but less synovial inflammation is seen. Bone marrow deposition is commonly seen in multiple myeloma patients. For patients on chronic dialysis, amyloid-related carpal tunnel has been seen.

**69**

reactivity.

*Pathologic Findings of Amyloidosis: Recent Advances DOI: http://dx.doi.org/10.5772/intechopen.84268*

**4.7 Atypical amyloid findings**

**Figure 7.**

extracted into the surrounding tissue [18].

correlation cannot substitute for amyloid typing.

embedded (FFPE) section compatibility.

Cases of intracellular amyloid deposition have been reported in few organs including cardiomyocytes, plasma cells, as well as the histiocytes and β cells of the pancreas [12–14]. Spheroid type (corpora amylacea-like) amyloid deposition is reported in pituitary adenoma, squamous cell carcinoma of the uterine cervix, and amyloidoma of the bone, jejunum, and colon [15–18]. One case of spheroid type amyloid deposition from our group in association with colon adenocarcinoma is identified [2] (**Figures 6** and **7**). Current hypothesis regarding spheroid type amyloid deposition is that during the process of amyloid removal by macrophages, amyloid is packed inside the macrophage, making spheroid formations that are

*Spheroid type amyloid deposition in colonic submucosa, Congo red stain under polarizer filter.*

**5. Immunohistochemistry and immunoelectron microscopy**

While the Congo red stain positivity and birefringence are the gold standard of confirming amyloidosis, they do not tell what type of amyloid is deposited. Considering managements and clinical outcomes vary drastically according to the types, further studies to identify the causative protein are critical. Clinicopathologic

Immunohistochemistry (IHC) is the most commonly utilized method for subtyping amyloidosis. IHC takes advantage of relatively specific binding properties of antibodies against different types of amyloid fibrils to illuminate the amyloid protein in tissue. A panel of antibodies for more common types can subtype the majority of amyloidosis cases. Such antibodies include those against ALλ, ALκ, AHγ, ATTR, Aβ2M, and AFib (fibrinogen). The method has been widely used due to low cost, ease of use, rapid turnaround time, and formalin-fixed paraffin-

However, there is one important pitfall in IHC. Because of heterogeneity of amyloid fibrils, nonspecific staining is common, and this potentially complicates the interpretation. For instance, the antibody against Aλ is notorious for nonspecific staining of amyloid other than Aλ. This diagnostic pitfall mandates the use of multiple comparative IHC stains to separate the true diagnostic positivity from the nonspecific reaction. In comparative IHC, subtyping of amyloid is determined by the specific amyloid with the strongest immunohistochemical

**Figure 6.** *Spheroid type amyloid deposition in colonic submucosa, Congo red stain.*

*Pathologic Findings of Amyloidosis: Recent Advances DOI: http://dx.doi.org/10.5772/intechopen.84268*

*Amyloid Diseases*

**4.6 Other organs**

**Figure 5.**

**68**

**Figure 6.**

*Spheroid type amyloid deposition in colonic submucosa, Congo red stain.*

can deposit within small-to-medium-sized arteries in the superficial cortex and leptomeningeal space and causes cerebral amyloid angiopathy. Cerebral amyloid angiopathy causes recurrent lobar hemorrhage. Furthermore, most Alzheimer's-

In the tongue, nodular deposition is seen, causing macroglossia. Gastrointestinal tract deposition of amyloid is common with polyps or ulcerative lesions. In the late stage, the cut surface shows yellow and waxy mural thickening. Clinically, it can cause motility disorders or stricture. Not uncommonly, vessels in the gastrointestinal tract can have amyloid deposition. In the respiratory tract, grossly nodular appearance is seen, and histologically, such depositions can be divided into four patterns including tracheobronchial, nodular parenchymal, diffuse alveolar septal, and lymphatic [11]. Skin depositions vary in size and shape, from papules to nodules and plaque. As an endocrine organ, the thyroid can present with goiter and is associated with medullary carcinoma. Localized nodular deposition in the bone causes amyloidoma. Inflammation including giant cell, lymphocyte, and spheroid structure has been reported [12]. Joint depositions are seen mimicking rheumatoid arthritis, but less synovial inflammation is seen. Bone marrow deposition is commonly seen in multiple myeloma patients. For patients on

affected brains show cerebral amyloid angiopathy as well.

*Amyloid plaque seen in Alzheimer disease, β amyloid antibody in IHC.*

chronic dialysis, amyloid-related carpal tunnel has been seen.

**Figure 7.** *Spheroid type amyloid deposition in colonic submucosa, Congo red stain under polarizer filter.*


Contents

Preface

There are numerous factors that contribute to the deterioration of structures and infrastructures over time, including fatigue failure induced by traffic loads, the effects of environmental conditions, and natural catastrophes such as earthquakes. Continuous monitoring of the structure is needed to provide an early warning of a potentially dangerous state and an assessment of the structure's changes over time, rather than only routine or critical event-based inspections. Thus, structural health monitoring (SHM) has recently become a popular area of research in structural engineering. SHM is a field that has grown tremendously over the past few decades. This book brings together the most recent studies and state-of-the-art methodologies to improve understanding of how SHM can be applied in the real world, as well as how it can be improved, by highlighting its practical, theoretical, and historical applications. The book also examines challenges in SHM and sheds light on the future trends of SHM techniques for different types of response measurement and their

**Dr. Gobinath Ravindran**

**Dr. Vutukuru Mahesh**

SR University, Warangal, India

SR University, Warangal, India

Penang, Malaysia

Department of Civil Engineering,

**Dr. Moustafa Moufid Kassem** School of Civil Engineering, Universiti Sains Malaysia,

Department of Mechanical Engineering,

applications in civil engineering structures and infrastructures.


*4.1. Single-Objective Optimization Approach*

After a set of boundary pipes *Nbp* are defined in the clustering phase, the first objective is to determine how many flow meters *Nf m* and gate valves *Ngv* to insert along the boundary pipes. Most researchers agree that fewer flow meters will reduce reconstruction and operating costs, as well as the initial cost of installing the flow meters, which are often more expensive than gate valves [6,17,47,49].

In addition, the positions of the gate valves and flow meters have a significant effect on network properties such as hydraulic performance, resilience index, leakage rate, and water quality. WDN sectorization should therefore be considered as a multi-objective optimization problem to maximize the benefits of implementing DMAs. However, to simplify computational demands, some hypotheses or heuristic processes have been proposed to convert a multi-objective problem into a single objective and apply evolutionary algorithms to achieve feasible or optimal solutions.

Because the number of feasible solutions is large, various heuristic optimization techniques have been studied [6,91–94]. Although the objective functions and constraints are different among the various approaches, they all aimed to achieve as high as possible a network performance after sectorization. The total power of a WDN is classified into the dissipated power at pipes (i.e., internal power loss) and the supplied power at node (i.e., external power supplied). Di Nardo et al. [6,17,18,49,92,95,96] suggested the objective function to maintain the hydraulic performance of the network at the lowest dissipated power that consequently maximizes the nodal supplied power by maintaining the nodal head as high as possible after sectorization. The objective was defined in the following equation.

$$\max \left( \gamma \sum\_{i}^{n} (z\_i + h\_i) Q\_i \right) \tag{13}$$

where γ is the specific weight of water and *zi*, *hi*, and *Qi* are the elevation, pressure, and water demand at node *i*, respectively. For a large and complex network, it is not easy to decide how many flow meters should be positioned among boundary pipes due to the trade-offs between hydraulic

performance and investment cost. To deal with this problem, Shao et al. [97] proposed a function that converted a dual-objective problem (i.e., hydraulic performance and cost) to a single-objective problem by considering the master-subordinate relationship of the two objective functions, which improved the computational efficiency.

In addition, a changing flow due to pipe failure can cause changes in velocity, energy losses in pipes, and pressure at nodes, especially in a looped network. This will cause changes in the pathway of water particles to the nodes. Moreover, if a node is being supplied at the minimum required pressure, it will not be able to provide the necessary flow and pressure. In the worst-case scenario, the network must ensure a capacity to provide a surplus power to overcome system failures. This is an approach proposed by Todini [98] to measure system resilience when redesigning a system or when system malfunction occurs. Based on that criterion, when reconstructing the system by creating isolated DMAs, several studies [34,36,46,60] have used a resilience index (Equation (14)) as an objective function for sectorization optimization. The objective function can be maximized to indicate that a greater surplus of available power leads to a higher network resilience such that:

$$I\_{\tau} = \frac{\sum\_{i=1}^{n\_n} Q\_i (h\_i - h\_{\min})}{\sum\_{r=1}^{n\_r} Q\_r H\_r - \sum\_{i=1}^{n\_n} Q\_i h\_{\min}} \, \tag{14}$$

where *nn* and *nr* are the numbers of demand nodes and reservoirs, respectively; *Qi* and *hi* are water demand and pressure at node *i*; *Qr* and *Hr* are the water discharge and total head of the source or tank r; and *hmin* is the minimum required pressure for adequate service.

For cost analysis, Gomes et al. [99] proposed an optimization model to design DMAs based on different decision-makers' options to reduce the total cost. Referring to different future scenarios for water demand (that will increase) and the infrastructure degradation forecasts, the cost of WNP was assessed. An objective function aims to minimize the cost of DMA redesign and first considers the cost of pipe reinforcement or replacement with flow meters and gate valves. Second, to ensure that the model approximates reality, the cost function is multiplied by the weight or probability of occurrence for each of the scenarios. A similar study that considers economic and energy criteria for DMA design can be found in Di Nardo et al. [75].

For reducing the leakage in WDNs, Creaco and Haidar [100] proposed a linear programming framework to optimize control valve settings. Accordingly, isolation valve closures, control valve installations, and DMAs creation are simultaneously optimized to search optimal solutions in the trade-off between installation costs, leakage, and demand uniformity across DMAs.

To solve the optimization problems mentioned above, evolutionary search algorithms have been applied. The GA [101] has been widely implemented by Di Nardo et al. [6,47,75,91,95]. Meanwhile, Shao et al. [97] improved the GA for faster and superior layout of flow meters and valves by modifying crossover and mutation mechanisms. In addition, the simulated annealing algorithm was presented by Gomes et al. [61,99,102].

## *4.2. Multiple-Objective Optimization Approach*

WNP is a complicated task and must achieve many goals. Zhang et al. [42] proposed a multi-objective optimizing approach for sectorization, in which three objective functions were used: the number of boundary pipes, network pressure uniformity, and water age uniformity. Zhang et al. [103] proposed a multi-objective optimization to obtain more reasonable schemes for sectorization of a WDN by simultaneously considering pressure stability, water quality safety, and system reconstruction costs. For pressure stability, the average pressure was minimized, but was still above the minimum pressure. Water age is the time spent by a water parcel as it travels from a source to nodes in the network, which represents the water quality in a WDN. Additionally, the costs of installing flow meters and valves should be minimized depending on the size and number of DMAs. However, if only the initial investment cost of these devices is considered, it is impossible to comprehensively evaluate the expense of the WNP. De Paola et al. [104] presented an objective function to deal with the total cost of sectorization, which also involves water leakage costs and energy consumption by pump operations.

Even if we consider all the criteria in the process of network sectorization, it is impossible to provide an optimal result due to trade-offs. The current partitioning techniques prioritize only a few representative sets of criteria, and do not fully address the best practical problems of DMA design. In an attempt to provide a comprehensive review of the criteria when dividing the network as close as possible to reality, Hajebi et al. [105] considered two sets of objectives in the sectorization task, the structural objective and hydraulic objective. For the structural objective, they considered the minimum cut size and minimum boundary pipe diameter. For the hydraulic objective of the network after segmentation, they considered four objectives, including minimization of the average excessive pressure at nodes, minimization of dissipated power, minimization of elevation differences in each DMA, and maximization of network resilience.

In another combination, a series of energy, operative, and economic criteria were optimized in the sectorization process [58,59]. Five objectives were addressed concerning the minimum deviation of the resilience index [95], which measures the capacity of the network to conquer system failures, the ability of the system to ensure an appropriate service pressure in the whole network, and minimization of the variation of the operational power, which assessed the reliability of a sectorization layout based on a pressure target. Operative criteria were also formulated as objective functions of pressure at nodes. When pressure dropped, a reduction in the leakage was expected. Variation of nodal pressure should therefore be minimized. However, pressure at nodes after sectorization needs to be higher than the minimum threshold required for service. To accommodate this constraint, a penalty cost for a nodal pressure deficit was added. Finally, the cost criteria when performing sectorization are also important. The cost of positioning and operation of flow meters are expected to be higher than that for boundary valves. Therefore, an objective function to minimize the cost for installing and operating the devices needs to be considered. Similarly, Brentan et al. [43] adopted a multilevel optimization concept to reduce the complexity of sectorization. In their approach, two groups of the objectives were minimized. The first one corresponded to structural costs, which were related to valve and flow meter installation, while the second group reflected hydraulic performance, such as minimum pressure and maximum resilience index.

Giudicianni et al. [88] recently developed a heuristic framework for dynamic partitioning of WDNs using multi-objective functions to address different goals for saving energy, water, and costs. Specifically, they proposed a method for zero-net energy management of a WDN using microhydropower stations [106] along the boundary pipes during the day and a reduction of water leakage at night.

To provide a comprehensive method for optimal DMA design, Galdiero et al. [107] proposed a decision-support tool that focused on water network segmentation by considering two objective functions. A total cost function including the initial cost for device investment and a daily cost due to water leakages were considered to minimize and compared as trade-offs with changes in hydraulic performance in terms of the maximum resilience index. To integrate different algorithms and multi-objective functions to the development of a decision support tool, Di Nardo et al. [18] developed advanced software called SWANP. A clustering model was implemented based on MLRBs, which are multiagent approaches to water network clustering. In the sectorization phase, an optimization algorithm was proposed using multi-objective functions to find optimal DMA configurations that complied with the level of customer service and considered the minimum pressure and maximum resilience index, and balanced the cost of investment and operation by minimum devices inserted to achieve isolated DMAs. SWANP was written on a Python environment with a user interface and was evaluated as an effective decision support system providing the manager with different optimal layout solutions.

Many optimization algorithms have been applied to deal with discrete nonlinear combinations and solve the multi-objective optimization of water network sectorization. NSGA-II [74] has been widely applied to multi-objective optimization problems. In terms of water network sectorization, NSGA-II has been used in many studies [103–105,107] to obtain the Pareto front, which contains a set of Pareto optimal solutions, thus providing support for managers charged with making more accurate and reasonable decisions based on their priorities and objectives. Zhang et al. [42] implemented an auto-adaptive many-objective algorithm [108] to solve the sectorization problem that shows some new features compared with NSGA-II. Giustolisi and Ridolfi [41] used a multi-objective GA to support network segmentation. Campbell et al. [58], and Gilbert et al. [94] applied an agent-swarm optimization algorithm [109]. In addition, the combination of three optimization algorithms of GA, particle-swarm optimization [110], and soccer-league competition [111] was suggested in Brentan et al. [44].

## *4.3. Iterative Approach*

In addition to the described optimization methods, iterative methods were applied to the placement of flow meters and valves [19,41,48,96]. An iterative method is a mathematical procedure that can generate a feasible solution using an initial guess to generate a sequence of solutions. The result is considered convergent when the initial set of criteria is met. Diao et al. [19] considered DMA size and minimum pressure as criteria, and used them as constraints in the heuristic-based iterative method to define the feedlines for each DMA. The approach determines the location of flow meters among boundary pipes between DMAs. In addition, Liu and Han [48] proposed an iterative method based on a heuristic procedure to determine the best location of flow meters subject to constrain head pressure at nodes. The iterative method permits the selection of one flow meter based on the shortest path from the source that can improve the pressure in each iteration. Di Nardo and Di Natale [96] inserted a certain number of flow meters on boundary pipes and then designed a procedure to alternately change the quantity and position of flow meters to achieve an optimal solution based on hydraulic performance constraints testing.

## *4.4. Adaptive Sectorization for Dynamic DMAs*

In normal working conditions, a DMA layout is permanent and optimized by WNP processes to satisfy the hydraulic constraints and network performance indices. In abnormal cases, such as pipe breaks, fire-fighting, and unexpected increases in water demand, permanent DMAs may produce failures in preserving or maintaining regular water supplies. To adapt to such conditions and overcome the drawbacks that a permanent DMA can cause, Giudicianni et al. [36,88] proposed creating dynamic DMAs that allow for expansion of existing DMAs. That is, the small DMAs are dynamically aggregated into larger ones using a semi-supervised clustering algorithm. This approach allows for a new configuration that always includes former DMAs and maintains the set of boundary pipes at each subzone. In some cases, by controlling the dynamic gate valves, the operator restores connectivity to its original configuration and consequently helps the utility periodically desegregate.

In addition, Wright et al. [112] proposed a method of integrating the advantages of DMAs in reducing leakage while improving network resilience and water quality by dynamically reconfiguring network topology and pressure control through optimizing valve settings and boundary pipes status using a sequential convex programming approach. The proposed approach leaned on the self-powered multifunction network controllers that allowed adjustments of the network topology and continuously monitored the dynamic hydraulics based on consumers' actions (i.e., the varieties of the system's water demands). In low demand periods, original DMAs were preserved to capture the minimum night flow within small isolated areas and maximize the ability to detect leaks. In peak demand periods, DMAs were then aggregated into larger pressure-controlled zones to maximize the resilience index and improve energy efficiency due to reduced internal losses that come with using larger DMAs. The core idea here was inserting the network controller associated with dynamically reconfigurable DMAs that allows a utility to monitor high-resolution, time-synchronized, dynamic pressure conditions of the network. Similarly, Perelman et al. [113] used a linear programming approach to automate reconfiguration of an existing WDN into DMAs. The network was reorganized into a star-like topology by identifying and decomposing the existing network into a main network and subnetworks based on graph theory. Center nodes were located in main pipes and played an important role as key connections between transmission main pipes with water sources and other nodes in the rest of the network. The proposed method provided a flexible tool for water utilities by allowing only existing valves to be closed, saving investment and operation costs for additional valve installations.

Ideas derived from DMAs' limitations in emergencies, especially in the case of fire-fighting, overcome this drawback. Di Nardo et al. [18,114] recently proposed a method that allows for the redesigning of static DMAs to dynamic layouts. A heuristic procedure based on a GA was developed to determine the number of gate valves that have to be motorized and remotely controlled to satisfy hydraulic performance in a fire-fighting event. This practical technique provided system operators with a quick decision-making tool to respond to unexpected incidents in the network and eventually leads to a smart water management paradigm. Unlike the approaches proposed above, Santonastaso et al. [115] developed a dynamic scheme for adjusting a WNP by accounting for the real positions of isolation valves present in the WDN. To do this, the adjacency matrix of the WDN was changed and replaced with a dual topology based on WDN sectorization and isolation valves. DMAs obtained in this approach allowed topology matrix segments to merge while inter-DMA boundary pipes were forced to be selected among the valve-fitted pipes that separated segments. Feasible DMAs were generated that did not require additional isolation valves.

To visualize the procedure of WNP technique in the abovementioned different phases, Figure 7 illustrates the procedure of WNP for a real-life WDN in Parete town, South Italy [47,49]. In this case, 4 DMAs were generated in the clustering phase based on the normalized spectral algorithm, and a heuristic procedure based on GA is applied in sectorization phase to locate the control devices while maximizing the total nodal power of the network.

**Figure 7.** Illustration of the water network partitioning (WNP) procedure implemented to a water distribution network (WDN) in Parete, South Italy (adapted from Di Nardo et al. [47,49]); (**a**) original water network, (**b**) clustering phase, and (**c**) sectorization phase.

#### **5. Performance Assessment of Water Network Partitioning**

As mentioned in Section 2, the water network segmentation to DMAs is expected to bring many benefits along with effective reduction measures for invisible water losses, manage pressure uniformity, and prevent network contamination. However, in some cases, it may also decrease the hydraulic performance and reliability of the network. To measure how this change affects network hydraulic behavior, performance indices (PIs) can quantify the benefits and drawbacks that DMAs bring. A PI test allows for the evaluations of the performance of the original networks compared with those of the divided networks. Most were estimated using a hydraulic simulation solver based on the demand-driven analysis. Most studies applied multiple PIs to evaluate the effectiveness of DMAs, such as resilience indices, pressure indices, uniformity indices, water quality indices, and fire protection indices.

The first to be mentioned is the resilience metric, which monitors the power balance of a water network, as proposed by Todini [98] in the form of Equation (14). According to this metric, WDN resilience is defined as the capacity to overcome sudden system (hydraulic or mechanical) failure. The resilience index is often used to evaluate the performance of a WNP as a comparison of network power before and after the sectorization. Most studies have stated that the resilience index is not significantly affected by network sectorization compared to its benefits [3]. Herrera et al. [116] proposed a graph-theoretic approach by adopting the K-shortest paths algorithm [117] to assess the resilience of larger-scale partitioned WDNs. To do this, all nodes in every DMA are aggregated into a sector-node, where a new DMA-graph is represented by sector-nodes and edges that are abstracted by sector-to-sector connectivity. A mapping function was used to transform the resilience of nodes to a sector-scale resilience. They showed that the resilience of individual nodes in the DMAs closely links to the corresponding sector-nodes resilience. This establishes a different way to identify DMA configurations that have a major impact on the resilience index.

If a resilience index evaluates the overall performance of the network, hydraulic statistical indices allow for the evaluation of the level of service that a water system supplies to its customers, providing managers information on pressure change in terms of mean, minimum, maximum, and spatio-temporal deviations. More specifically, Di Nardo et al. [118] proposed several indices, such as a mean pressure surplus and mean pressure deficit compared with the design pressure.

On the other hand, water quality is measured by water age in a network and is influenced by network topology, flow velocities, and pipe lengths. The age of the water affects residual chlorine levels. Lower chlorine induces bacterial growth, and higher values indicate worse performance. Many studies used the water age index as an indicator to assess the impact of DMA design on water quality. Grayman et al. [10] and a series of studies by Di Nardo et al. [118] illustrate that after incorporating DMAs into a WDN, there was no systematic difference in the computed average water age between alternative scenarios. Although there can be significant variations in water age by node due to valve closures, when considered as a whole, no homogeneous difference was found.

Meanwhile, partitioning a WDN into subnetworks with gate valves can prevent the spread of contamination in the case of malicious attacks. Di Nardo et al. [28,119] proposed a method that uses a simple backflow attack with cyanide to investigate the effects of network partitioning. Grayman et al. [10] proposed an index to quantify the potential health impacts from contamination incidents in the WDN.

Several hydraulic uniformity indices [44,48,120,121] have been developed to evaluate the performance of DMAs. The size uniformity index reflects the cumulative demand deviation of all DMAs compared with a hypothetical DMA with average demand, for which a smaller value indicates a better performance. Pressure uniformity was suggested to guarantee that all nodes belonging to a certain district would have similar pressure patterns. A lower index value indicates better performance. Total head uniformity is also used to measure the variance of total heads along the nodes, which has the same meaning as pressure uniformity. Liu and Han [48] proposed a decision-making framework to determine the optimal DMA design by quantifying various indices, such as DMA uniformity, modularity index, and resilience index. Similarly, evaluating the benefits brought by DMAs in terms of cost-benefit analysis allows managers to make sensible decisions and create functional and efficient DMAs. Ferrari and Savic [25] proposed a comprehensive method that considers alternative DMA configurations to show the savings that utilities can obtain by considering three indices related leakage reduction, burst-frequency reduction, and pressure-sensitive demand

reduction compared with the original network. Pressure reduction across the network was the main factor leading to reducing leakage and burst frequency. The study provided a decision-support tool for economic performance analysis of various DMA layouts.

In the case of a fire, while water demand is high for fire-fighting at a few nodes, the network must still have the capacity to supply enough water to users, especially during peak demand hours. This superposition of demand creates energy-loss leaps in pipes, leading to lower pressures at that time. Moreover, when creating isolated DMAs, some pipes feeding a district are closed and this could have negative impacts on the amount of flow entering a DMA. To test this situation, Grayman et al. [10] and Di Nardo et al. [118] developed a fire protection index based on the number of nodes with a pressure lower than the required pressure designed for the fire-fighting event. Those results indicated that some negative pressure values were occurring while most of the nodes had acceptable pressure. However, a significant difference was found between looped and branched networks.

WDN is a dynamic system in which pressure can vary significantly due to variations in water demand at nodes. Addressing spatial-temporal variability of water demand in the network, Di Nardo et al. [122] proposed a procedure for WNP under stochastic water demand and quantified its effects on hydraulic performance. The study revealed that by applying random variability of water demand, the magnitude of pressure distribution within the network was affected significantly. This led to a decrement of surplus pressure and network resilience compared with the constant-demand condition. To create feasible DMAs, especially for a WDN characterized by a small deviation between the surplus pressure and required standard pressure, spatial-temporal variability of water demand should be considered in WNP.

## **6. Discussion and Future Work**

This paper provided a comprehensive review of the relevant studies on WNP over the last decade. The WNP procedure consists of two basic phases. First, the clustering phase involves the formation of the sizes and dimensions of DMAs as well as the definition of the boundary pipes that feed or interconnect DMAs. This phase is commonly associated with use of a clustering algorithm. In this study, six commonly applied algorithms such as (i) Graph theory, (ii) community structure algorithm, (iii) modularity-based algorithm, (iv) multilevel graph partitioning, (v) spectral graph algorithm, and (vi) multi-agent approach, are presented and discussed in-depth to understand how they work and handle in formation of the feasible DMA configurations. These algorithms are commonly based on the graph theorem that relies primarily on the network's topology. Since WDN is an infrastructure system with particular properties, the water network clustering algorithm allows for tailoring by appending weights to pipes or/and nodes to mimic distributing loads across the WDN. Many criteria for DMA design, such as hydraulic performance, network topology, system reliability, water quality, and cost-benefit ratio, are considered in this phase to minimize the number of boundary pipes and its goal is to define the reasonable size and configuration of DMAs.

Second, the sectorization phase is a physical segmentation process that identifies the position of gate valves and flow meters among the set of boundary pipes to satisfy operational constraints. This task requires the designer to apply an optimization algorithm or heuristic procedures to ensure that the locations of devices will have the least negative impact on the hydraulic performance of the network, minimize the energy use and leakage and be cost-effective.

The improvements and innovations in WNP developed to date often come from innovative approaches, either with the clustering algorithm or sectorization optimization. Those innovative features have emerged from combinations of clustering algorithms and alternating with flexibility or/and developing various objective functions based on the different criteria designs to propose a heuristic procedure for creating the most reliable DMAs. Many different approaches have been proposed for the automated creation of DMAs. However, several shortcomings remain to pursue in the future.

**Author Contributions:** Conceptualization, X.K.B.; writing—original draft preparation, X.K.B.; writing—review and editing, D.K. and M.S.M.; supervision, D.K. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by the EDISON\* Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (Grant No. 2017M3C 1A6075016). \* Education-research Integration through Simulation On the Net.

**Conflicts of Interest:** The authors declare no conflict of interest.


**5. The structure of integrated risk management**

Achievement of the objectives of integrated risk management within an organization presupposes the meeting, in a logical sequence, of specific and required activities, as follows: setting the context, setting the objectives, risk identification, risk assessment, setting a risk response, implementation of control measures, information and communication and monitoring.

#### **5.1. Integrated risk management process**

Integrated risk management is structured on component elements of the COSO model, indicating that the control environment is defined by the internal environment and risk assessment consists of setting goals, identifying events, risk assessment and risk response.

### *5.1.1. The internal environment*

It represents the theoretical and conceptual stage of risk management process, which presupposes an organizational culture on risks and knowledge of risk management operating concepts, and whether they are implemented and known at all levels within the organization.

This stage involves carrying out specific activities to implement risk management within the organization, as follows:

In relation to the means of establishing the context of implementation of risk management it is established and designed risk management policy, objectives and tasks of the implementation of risk management methods and methodologies for the identification, evaluation, treatment and control risk. At the same time, it is determined the structure responsible for risk management, the powers and responsibilities of it, taking into account the fact that *"management activity it means to commonly achieve the necessary objectives for the final of the organization*11*"*.

The characteristic of this work is the tone given by the organization on risk management and methodology they use in risk management and how are communicated the concepts of risk and the response of staff on risk management philosophy.