\r\n\tWithin this frame, the current book, published by InTech Open, will aim at providing the reader an update on ANS monitoring and its role in health, both physical and emotional.
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Aslanidis received his Doctor of Medicine degree from Plovdiv Medical University, Bulgaria and his PhD degree from Aristotle University of Thessaloniki, Greece. He served in the Hellenic Army Force as a medical doctor and then worked as a rural physician in Outhealth Centre, Iraklia and Serres’ General Hospital, Greece. He moved to Thessaloniki where he completed his residency in anesthesiology in 'Hippokratio” General Hospital, fellowship training at AHEPA University Hospital in Critical Care, and then a postgraduate program in Prehospital Emergency Medicine. He served as EMS Physician and Emergency Communication Center Medic at Hellenic National Centre for Emergency Care before moving to his current post as consultant-researcher at the Intensive Care Unit of St. Paul General Hospital of Thessaloniki, Greece. 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This is particularly true in Asia, Africa and the Middle East where new rail networks have been commissioned and new rail networks are being designed and constructed. Railways are complex distributed systems with capital expenditure ranging from a few $100’s million to billions of dollars. Rail projects usually consist of two main disciplines—civil and systems, with the civil component costing anywhere between 60 and 80% of the contract value. It is not unusual for rail projects, particularly transit/metro projects, to engage the services of technical specialist from a variety of technical disciplines such as architecture, landscape, fire and safety, roads, utilities, etc.
The integration of ‘vertical’ construction elements such as stations, parking facilities with ‘horizontal’ construction elements, such as track, bridges, and roadways, creates a need for a comprehensive set of design and construction services that is not normally found in other transportation projects. The nature and specialisation of these components usually requires two different entities to lead the design and construction efforts of each component. However, and in recent times, it is more common to award rail projects as a design and build contract in which the design and build contractor is a consortium comprising civil and system solution providers. Design and Build is a method of procurement in which a single legal entity takes full responsibility and sole liability for both design and construction [1]. The single legal entity may be a multi-disciplinary firm with in-house design capabilities or a consortium capable of providing a total solution. The design and build contractor is liable for all design and construction cost and must usually provide a firm fixed price in its proposal—these are typically lump sum contracts. In these type of projects, the design and build contractor commits to an aggressive schedule and implements strategies to enable the works to be completed to schedule and cost [2]. The design phase of any construction project is cyclic, repetitive and evolutionary involving designers from various design groups such as structural, mechanical, electrical and plumbing, architecture, road works. Often, these designers perceive their design scope with a unique and independent view neglecting the holistic view of the project. It is therefore not surprising that evidence exist that suggest that the design and construction failures originate from this ill-structured design process. It is therefore important that adequate effort must be taken to ensure a robust design strategy is in place from the onset and that all relevant stakeholders buy in the strategy [3]. One strategy implemented to reduce project delivery time is to reduce the design delivery time through the parallelism of sequential activities and it is not surprising therefore that many researchers have explored this aspect [4, 5, 6, 7, 8, 9]. In this Chapter, a synopsis of the application of concurrent design principles and its applications to railway design and build projects is provided.
In a typical design and build project, the owner would have undertaken a 30% design effort. This design effort enables the owner to develop specific functional and performance requirements, establish preliminary stakeholder agreements, establish the alignment, secure land requirement, establish the capital cost estimate, minimise residual owner residual risk, etc. The owner’s 30% design is usually supplied as part of the Request for Proposal (RFP)/Invitation To Tender (ITT) on an information basis with some components of the same, such as the alignment, supplied as owner’s requirement. The design and build contractor is expected to complete the 70% design effort through a staged process that includes preliminary, detailed and final design. The completion of these design phases represents major milestones in the design life cycle and thus are typically referred to as design control points. The design and build contractor is expected to have performed a 100% design effort to complete the design delivery. To eliminate rework, it is preferable that design is complete or substantially complete before construction commences, thus an effective management of the design process is crucial to minimise cost and schedule overrun.
The design team is required to complete the design effort in earnest such that construction activities can proceed much earlier. This pressure on design has the objective of reducing the delivery time and minimising delivery cost. This task becomes more difficult as in most cases Systems design tends to follow a sequential progression of plans, specifications and products that are baselined and placed under configuration control. This sequential process, referred to as the Vee Model (also known as Verification and Validation Model), is usually specified in the Contract and mandated by International Standards such as IEC 62278 [10]. Furthermore, infrastructure owners are placing increasing emphasis on quality and reliability as well as the value proposition of the design and build contractor. The ability to deliver to schedule and cost is becoming a major differentiator in railway infrastructure projects.
The parallelism of sequential activities is in effect the application of concurrent engineering principles. There are numerous definitions for concurrent engineering, but the common theme in all such definitions is a holistic approach to product development that considers all life-cycle components and influences from the onset. For the purpose of this Chapter, the following definition by Cleetus [11] and Winner et al. [12] is preferred:
Concurrent engineering as a systematic approach to integrated product development that emphasises response to customer expectations and embodies team values of cooperation, trust and sharing in such a manner that decision making proceeds with large intervals of parallel working by all life-cycle perspectives early in the process.
Concurrent engineering is intended to ensure that contractors, from the onset of a railway infrastructure design-build project, consider all elements of the final system from conception through disposal, including quality, cost, schedule and user requirement [13, 14]. However, the overlapping of design activities may result in serious consequence if not managed effectively. Concurrent design is a holistic design approach that considers the constructibility of the product as part of the design and avoids design changes to enhances its constructibility.
The main objective in applying concurrent engineering to design is to reduce waste that may occur in the design cycle and to achieve continuous improvements in the design flow and output. This is achieved by viewing ‘design’ as [15]:
A transformation of inputs to outputs;
A process of information flow from one activity to another;
A process of value generation.
Design is performed by a group of subject matter specialist whose main objective is the transformation of a client’s requirements into outputs that comprise design decisions and actionable design documents. Tzortzopoulos and Formoso [16] identified three perspective of design:
Conversion: In this view, the design is apportioned into sub-elements and assigned to a specialist who interpreted the client’s requirements and converts the same into design decisions. Deshpande et al. [15] notes the tendency of occurrence of non-value adding components in the design when it is analysed simply as a conversion of inputs to outputs. Deshpande et al. postulated that such occurrence results in an increase in the time to complete design and/or insufficient time to generate optimal design solutions [17].
Information Flow: Another school of thought, first proposed by Huovila et al. [18], suggest that the design process be viewed in terms of bi-directional information flow from stakeholders to the designers. A key principle of this thought is the identification and eradication of non-value adding activities from the design process.
Value Generation: This school of thought on design is driven by the desire to achieve the best possible design outcome for the client. Huovila et al. [18] suggest that the process of value generation is dependent on the quality of information available to the designers, as well as the ability of the design team to transform complex, uncertain, and conflicting requirements into solutions that generate value for the client.
Ballard and Koskela [19] argued that it is necessary to integrate the three thoughts expressed above for effective design management. The quality of design can be improved by increasing the quantity and quality of available information with respect to customer needs and requirements. Requirements management in terms of apportionment, assessment, analysis and traceability is therefore a key component of design management. Tzortzopoulos and Formoso [16] provided practical guidelines for the implementation of lean concepts in the design process, these guidelines include:
Identification and elimination of non-value adding activities in design;
Increment of output value through detailed assessment of client requirements;
Reduction of variability in the design process;
Limiting the approval cycle times for design documents;
Implementing design freeze and gate review concepts; and
Establishing meaningful Key Performance Indicators (KPIs) and implementing continuous improvement in the design processes.
The design life cycle is typically separated into four stages – conceptual, preliminary, detailed and final design. Some projects specify a three-stage process consisting of preliminary, detailed and final design—thus for such projects, the initial design effort required represents a 60% design effort. Irrespective of the design life cycle, the Contractor is required, at the onset of the project, to assess and plan the works in terms of work breakdown structure that represents a detailed level at which appropriate reporting and earned value can be assessed [4]. The first step is to break down the design project into appropriate level of detail for budgeting and measuring progress. In this step, the work is broken down to level of details consistent with the requirements for scheduling and determining earned value. In most cases, an experienced rail design-build contractor will implement a breakdown, gained from experience on similar projects, based on an estimated number of design documents to be produced. The output of this first step, among others, is an estimate of the total quantity of design efforts in terms of configurable items (i.e. drawings, calculations, reports, software, specifications, etc) and identification of the design stages at which each configurable item will be delivered. Such a list is referred to as a Document Submittal Register (DSR) or as a Contract Data Requirement List (CDRL). It is acknowledged that the DSR is a live document that is updated throughout the life of the project as the design matures, however in reality attempts are made to freeze the DSR at final design.
The second step is to identify the design interfaces between the design work packages. These design interfaces determine the sequential dependency among design tasks. A matrix may be used to illustrate the dependencies between design work packages and between design tasks. In such a matrix, the columns represent predecessors awhile the rows represent successors. The matrix can be used to identify sequential relationships between design tasks. The third step is to separate the systems into independent groups. This involves grouping objects into homogenous groups, based on a set of common features. The goal of this process is to group dependent systems into manageable packages. The final step is to develop a network schedule, this may be represented using the precedence diagramming method or probabilistically using Programming Evaluation and Review Technique (PERT) [20]. A Graphical Evaluation and Review Technique (GERT) may be used to simulate and assess alternative branches of design activity loops [21].
A sequential design life cycle is illustrated in Figure 1 below. In this life cycle, the development progresses through several defined phases. A detailed review of the differences and similarities between a sequential and concurrent logic is provided in [22].
Sequential design logic.
This design logic is characterised by a sequential pattern where information about the product is slowly accumulated in consecutive stages. A stage commences only when the preceding stage is completed and has supplied complete and final information. This design life cycle is aligned with systems engineering principles and best suited for the system design component. Each stage must be completed before the next stage begins.
Concurrent engineering involves reducing the total delivery time and cost of a project by overlapping activities (parallelisation of design activities) that are normally performed in a sequential manner. A core principle of the concept is the need to proceed at risk with an assumption that a specified performance will be obtained from a component, even before that performance has been demonstrated. The risk is managed on the basis of the integrity and certainty of the available information.
The extent of the overlap between two activities depends on the nature of the information exchange between these activities because it is the exchange of information that determines what work can start on the downstream activity. The extent to which two activities can be effectively overlapped depends on the relationship between those activities [22, 23]. Prasad [22] identified four types of relationships that are possible between design activities: (1) dependent activities, (2) semi-independent activities, (3) independent activities, and (4) interdependent activities. For dependent activities, the commencement of a downstream activity is dependent on the receipt of information from an upstream activity. Semi-independent design relationships commence upon the receipt of partial information from other activities. Independent design relationships are characterised by those activities that require no information from another before another activity can start. Interdependent design relationships are characterised by a bi-directional exchange of information between activities before either can be completed [24].
With respect to the identified design relationship types, only independent design activities can be overlapped without the risk of incurring delay or rework. There is an inherent risk in the overlapping of dependent activities. This inherent risk is due to the fact that a downstream activity, in a dependent activity relationship, must commence before all necessary information is available from a upstream activity. Thus changes in the upstream activity that impact assumptions made at the commencement of the downstream activity may increase the severity of the risk of delay or rework. This risk can be mitigated, in part, through increased communication and exchange of preliminary information between the upstream and downstream design activities. In other words, it is preferable not to concurrently design systems that belong to the same package.
One way that concurrent engineering characterises the exchange of information is through the concept of information evolution of the upstream activity and the sensitivity of the downstream activity or activities to that information evolution [25]. Information and knowledge in an upstream activity can develop rapidly or slowly. For the downstream activity, the sensitivity to changes in the upstream information can be significant depending on the level of rework required. Figure 2 illustrates the concept of a concurrent design logic. While applying concurrent design logic, there are a number of conditions that need to be taken into consideration; the information exchange between a potential overlapping pair of activities, the management strategy used to facilitate the overlap between the pair(s), the likelihood of rework relative to the degree of overlap, and the impact of the rework on cost and schedule. These factors are analysed in the proceeding sections.
Concurrent design logic.
Concurrent engineering can be viewed as comprised of three basic components:
Simultaneity of Activities: In a sequential design flow, the total time, Ts, required to complete the design activity is given as:
In the case of simultaneity of activities, the total time, Tc, required to complete the design activity is equal to the time duration of the activity with the maximum time duration:
Figure 3 illustrates the time required to execute the design activities in a concurrent design logic. Comparing the time required to complete the design activity in sequential design logic with a concurrent design logic, it is clear that a concurrent design logic offers a time saving of ΔT = Ts − Tc
Concurrency: The multifunctional design teams implement design concurrently (i.e. Activities 1, 2 and 3 are performed concurrently by different design teams) and interactively make decisions on works. Simultaneity of design activities without dynamic interaction of the various design teams does not assure concurrency. For example, consider a case of a simple overlapping of design activities in which communication is an acknowledgement of the conditions for commencing a task and those that underpin its completion. True concurrency of design implies interaction between the two activities in order to obtain the best decision, i.e. the two design activities ‘concur’ simultaneously for the best decision through dynamic interactions (communication), or solutions.
Simultaneity and concurrency need to occur at the onset or in the early stages of design process to ensure effective implementation of a concurrent design logic.
Time saving due to concurrent design logic.
The greatest impact and benefits of concurrent engineering is evident at the design stage. The design decisions made in the early design stages (i.e. conceptual and preliminary design phases) have a significant impact on the constructibility of a product, as between 70 and 80% of the construction cost is determined by design [26, 27]. Thus, cost reduction efforts must be an integral component of the design effort. In the following, we review factors that need to be considered to achieve a successful concurrent design output.
As previously mentioned, concurrent design logic can be viewed as an information processing system in which individual design activities are modelled as information processing units that receive information from proceeding activities and transform the information received into new information to be passed on to subsequent activities. With reference to Figure 2, preliminary information of the design Activity 1 is available ts and is continuously modified until the end of the activity. Activity 2 can start at any time between ts and tf. Evolution describes the rate at which design information is generated from the start of an activity through the completion of the activity. It is acknowledged that in practise a quantitative assessment of information evolution may be impracticable and thus a qualitative approach is favoured. There are four key determinants of evolution:
Design optimisation: The level of optimisation performed on design elements or the number of design alternatives evaluated
Constrain satisfaction: The flexibility of design elements in satisfying constraints
External information exchange: The amount of information received from or reviewed by external sources; and
Standardisation: The level of standardisation in the design process and/or design product
Each of the determinants of evolution listed above relies on activity iteration as a determining factor. Design information in those activities with iteration evolves slower than activities without iteration. It goes without saying that an activity without constraint or pressure will evolve naturally and that this natural evolution tends to produce the best design outcome for that activity, however, most design is performed under some constraint, and this is particularly true under a design and build project. Such constraints results in actions that alter the natural evolution of an activity; for example, actions resulting from time constraint may results in the reduction of the time taken to complete an individual activity or a reduction in the overall design schedule.
However, the gains from overlapping must be balanced against the potential of rework (cost and time) which results from the modification of the upstream information. When preliminary upstream information is utilised by the downstream activity too early, future changes may have to be incorporated in time consuming subsequent iterations that result in an increase downstream duration and effort. The amount of rework required, if preliminary information changes, is a function of the sensitivity of the downstream activity to changes in the upstream information.
Krishnan et al. [28] qualified sensitivity as a measure of the amount of rework required in a downstream activity as a result of information evolution in an upstream activity. The following conditions impact the sensitivity severity of the downstream activities to changes in upstream information and thus increase the risk of rework:
The downstream design is near a constraint or boundary;
The downstream design depends on one key upstream input; or
The downstream design is integrated such that changes cannot be isolated.
Small changes in the upstream information could result in extensive rework with a major cost and schedule impact to a highly sensitive downstream activity. On the contrary, a low sensitivity downstream activity can accommodate changes in information from an upstream activity such that minimum or no rework is required with minimal cost and/or schedule impact. Bogus and Molenaar [29] identified three determinant factors that influence the sensitivity of an activity:
Constraint sensitive: The proximity of the downstream design to a constraint or boundary;
Input sensitive: The level of dependence of downstream design on specific inputs from other activities; and
Integration sensitive: The ability of the downstream design element to be separated from the entire system.
The combination of an upstream activity with a fast or slow evolution and a downstream activity with a low or high sensitivity results in four possible combinations of evolution and sensitivity. These four possible combinations are major considerations in the assessment of the probability of rework for an activity pair. Roemer et al. [8] and Bogus and Molenaar [29] defined rework as the “increase in time and costs, direct and indirect, that are required to correct some of the work in the downstream activity due to incorrect or changing information received from the upstream activity”. This definition highlights the importance of the need to ensure the integrity of the underpinning assumptions and information flow from the upstream activity.
The need to commence railway construction activities in earnest serves to meet the aggressive schedule imposed through the contract. These projects, typically structured under International Federation of Consulting Engineers (FIDIC) rules, place the Contractor as the majority owner of associated risk. The design and build contractor therefore needs to put in place adequate processes and control to manage the delivery and in particular the cost. It is beneficial to apply the principles of concurrent design at the commencement of the project, with due consideration of requirement management, design freeze, over-design, etc.
Eger et al. [30] defines design freeze as a “binding decision that defines the whole product, its parts or parameters and allows the continuation of the design based on that decision”. Design freeze allows structuring and planning of the design process [30]. Freezing a design or key components of a design aims to reduce the likelihood of engineering changes, however, any change required to be implemented after a design freeze may result in high rework cost and potential delays. Design freeze can apply to different stages of the design life cycle. Figure 4 shows a typical design gate review process; it is easily recognised that the logic shown in Figure 4 is a sequential logic, however in reality it is possible to apply design freeze in a concurrent design process to facilitate the early commencement of a downstream activity, however, depending on how it is implemented, design freeze in a concurrent design logic can be viewed as performing the design activities in sequential manner using incomplete preliminary information from upstream activities. In this case, the risk of possible design changes increases with greater degrees of overlap. There are many advantages of the application of the concept of design freeze; it can facilitate the early procurement of long lead items; it can also assist in the reduction of the risk of rework and can set preliminary information from an upstream activity as a basis for further work. Once design freeze has occurred, changes to downstream activities resulting from evolution of preliminary information of the upstream activities needs to be carefully analysed before proceeding. Alternative implementation strategies should be considered and all changes should follow a change control process.
Design gate review.
Unlike design freeze, overdesign adds a margin of safety to the design as an attempt to mitigate potential errors in the information flow during overlapping periods. It can be defined as the process of implementing conservative assumptions, in the downstream activity in lieu of incomplete preliminary information transfer from the upstream activity. As an example, one may make conservative assumptions on the required size of technical rooms, while the systems design is still in its infancy, with the view to allow construction of a station or depot to proceed. There is, however, an inherent risk that the margin of safety applied might not be adequate and thus resulting in an underdesign scenario. This may result if the initial assumption is based on previous project experience without adequate analysis and resolution of the current contract’s requirements, particularly those concerning the civil-system interfaces. Such a scenario may result in rework with cost and time impact. There is therefore a balance to be maintained between the robustness and integrity of the underpinning design assumptions and the cost of implementing the design. A trade-off also exist between the degree of overlapping and the certainty of upstream information.
Standardisation is the process of adopting a design solution to be used repetitively on a project. Such practice speeds up the evolution of upstream activities and enables early information transfer from the upstream activity to the downstream. There is a likelihood of cost increases due to lack of design optimisation. In recent applications of this technique on a design and build project with 22 stations comprising of elevated and underground stations, two archetypes stations representing an elevated and underground stations where processed through design completion and these archetypes acted as the design standards for the remainder of the stations designs. This approach resulted in increased construction productivity. It should be noted that subtle difference between stations—in terms of size, layout etc.—may require additional design effort over and above that established in the standard design. It is to be recognised that standardisation in terms of design processes and procedures further contributes to an increase performance of the construction output and the overall project schedule.
As mentioned in Section 2.1, the tendency is for Systems design to follow a sequential design logic, partly because of the safety-critical nature that rail systems serves within the railway infrastructure and partly because the systems assurance process forces a sequential logic review. That said, in most design and build projects, the initial delay manifest from the civil design and construction phases. Systems, being the last major component of the Works, therefore are under constant pressure to mitigate the delays incurred from a predominate civil upstream activity. The systems activities under such pressure tend to be Systems installation and Test & Commissioning. The fact that systems design tends to follow a sequential design logic does not exclude the application concurrent engineering to the elements of the systems design. In fact, applying concurrent engineering principles of systems design ensure the timely resolution of interface issues between civil and system. Zhang and Chen [31] demonstrated the successful application of concurrent engineering on the design and fabrication of a rolling stock. The driver for applying concurrent engineering was stated as to shorten product engineering delay, improve locomotive design and capitalise knowledge. Park [32] demonstrated that concurrent design principles can be applied to safety-critical system using a model-based approach. Furthermore, while IEC 62278 implies a sequential logic, ISO/IEC 24748 [33] emphasises that projects should integrate the concurrent design of products and their related life-cycle processes. It goes on to state that ‘concurrent engineering should integrate product and process development to ensure that the product(s) are producible, usable, and supportable’.
This Chapter discusses the application of concurrent engineering concept and principles to the design process of a design-build rail project. It is identified that concurrent engineering is a logical approach to achieve a reduction in project delivery time and cost. It is highlighted that the key objective of meeting the desired project duration and cost expectations is through the overlapping of dependent activities. It is noted that overlapping should be approached in a systematic manner to reduce costs and risks. While concurrent engineering is not a term typically associated with design and build rail project, the concept is not alien to the rail construction industry as attempts at mitigating delays, avoiding potential delay penalties and cost overrun due to retrofits and delays always results in an ‘accelerated’ schedule which typically exhibits the application of concurrent engineering logic in what was otherwise a sequential logic. It is highlighted that executing the design activities of a railway design and build project concurrently will result in improvements in quality, time to deliver, cash flow and profitability, etc. It is crucial that the designers, schedulers and planners work together from the onset to develop the project schedule reflective of concurrent engineering logic.
The congenital anomalies of the urinary tract include a large number of diseases caused by anomalies in the morphogenesis of the urinary system. These anomalies include obstructive and nonobstructive dilatation of the urinary tract that can be associated with alterations in the number, size and/or position of the kidneys [1, 2].
We will discuss the congenital anomalies of the urinary and genital tract, with a short review of kidney abnormalities. These malformations may coexist within the same case, and this is due to their common embryonic origin [3].
The reno-urinary anomalies occur more frequently in males than in females, the ratio being 2.5:1 (M-F), and there are many cases with family aggregation. The incidence is 3–4 at 1000 lives or 1–5% of all pregnancies [4, 5]. If including all cases detected at post-mortem fetal autopsies, the prevalence of these malformations is much higher [2].
The urogenital system is represented by two major components: the urinary system and the genital system. Embryological and fetal kidneys, genital tract and the urinary system develop from intermediate mesoderm. The rhythm of growth and development of the collector tubes differs greatly during pregnancy. Until 15 weeks of gestation, the rhythm of development is very rapid and later decreases [1, 2].
The urinary tract is almost entirely developed from the intermediate mesoderm. The evolution implies different stages in development: pronephros, mesonephros and metanephros. These stages will appear successively in the craniocaudal direction and coexist over time. Intermediate mesoderm is divided in the upper cervical and thoracic region, resulting in nephrotomes [2, 3].
The mesonephric duct will give rise to the ureteral bud after the formation of the pronephros. This, after 15 generations of divisions, will lead to the formation of the ureter, the calves, the collector tubes and the kidney pelvis. The lack of formation or agenesis of the pronephros or of the mesonephric duct can lead to the total or partial absence of the kidney or to other anomalies of the reno-urinary tract [4, 5].
CAKUT (congenital anomalies of kidney and urinary tract) may be part of multi-organ processes in single-gene disorders, with dominant or recessive inheritance, as we can find in Fraser syndrome, the branchiootorenal syndrome, Kallmann syndrome, Ehlers-Danlos syndrome and others [5, 6].
The genitalia differentiation, which leads to female or male gender, starts at 7–8 weeks of pregnancy and finalizes at 12–13 weeks. Every fetus will develop female characteristics, because at the beginning of gestational period, the Mullerian and Wolffian structures coexist. If the Mullerian structure will suffer atrophy, due to testosterone and anti-Mullerian hormone effects, male sex structures will develop from the Wolffian structure, and the fetus will become a male. In the opposite circumstance, the fetus will become a female. In conclusion, from the embryological point of view, an individual could be a female if the masculine features will not develop [7, 8].
Congenital urinary abnormalities are often associated with the kidney anomalies, and there is a wide range of malformations resulting from disorders in the normal development process [9].
Malformations of renal parenchyma may occur due to the abnormal nephron development—in cases of renal dysplasia, renal agenesis and renal polycystic disease. The migration abnormalities of kidney embryo buds are found in renal ectopy and in the mismatched malformations [10].
Abnormalities in the development of the urinary tract system cause duplicated collective systems, posterior urethral valves and obstructions of the pyeloureteral junction. Defects may be unilateral or bilateral, and several types of defects may be associated [1, 2, 3, 6, 7].
The anomalies of the urinary system can be divided into nephropathies and uropathies:
Nephropathy involves the renal parenchyma and refers to multicystic kidney disease (MCDK), renal dysplasia disease, renal agenesis defect, congenital polycystic kidney disease and other anomalies (nephromegaly, trisomy 13, Meckel syndrome, Beckwith-Wiedemann syndrome) [6, 7, 8].
Uropathies represent the pathology of the urinary tract, and by the site of the defect, they can be pyeloureteral and ureterovesical, or they can refer to the vesicoureteral reflux and to the posterior urethral valve. Many authors also consider here the urachal fistula, the urachal cyst and the exstrophy of the urinary bladder [10, 11, 12].
For a better understanding of urinary tract abnormalities, we will summarize the classification of kidney malformations that may accompany these anomalies:
Anomalies in number
Complete bilateral renal agenesis is a rare condition, not compatible with extrauterine life. The physical appearance of the babies is very characteristic (the so-called Potter syndrome). The absence of the kidneys may be suspected before conventional postmortem autopsy. Fetal ultrasound examination is very difficult, due to the absence of amniotic fluid.
Unilateral renal agenesis or the ‘congenital solitary kidney’ is probably the most difficult diagnosis of renal malformations. There is a consensus in terms of a definitive diagnosis, autopsy being the only conclusive method.
Renal aplasia—there is a fetal bud, but it does not develop into a normal functioning organ. The pelvis and ureter are usually absent or are rudimentary.
Supernumerary kidney is the rarest anomaly and consists of a third kidney with excretory cavities and its own vascularity, completely separated from the other kidney [1, 2, 3, 4, 5, 6, 7, 8].
Renal size abnormalities
Kidney’s shape abnormalities
Lobular kidney. There is a persistence of fetal lobulation.
Kidney fusion. There are bilateral symmetrical or asymmetrical mergers or unilateral asymmetry.
The kidney in the horseshoe. In 90% of the cases, kidneys join at the lower pole through a parenchymal or fibrous bridge.
Bilateral asymmetric mergers. One of the kidneys is smaller than the other.
Unilateral asymmetric fusions. There is a single kidney mass with a crossed ectopic kidney, known as ‘the sigmoid kidney’, usually located in the pelvis [7, 8, 9, 10].
Renal position abnormalities
Ectopic kidney. A birth defect given by an abnormal (unilateral or bilateral) kidney position. The ectopic kidney is more often located on the left side. There are several ectopic kidney types: the caudal (lumbar, iliac, sacral) kidney, the cranial kidney and the crossed kidney.
Renal dystopia. Initially, in embryonic life, the hill and pelvis are located in the anterior part, and then they undergo a rotation around the longitudinal axis, until they reach the median side [1, 2, 3, 4, 7].
Multicystic renal dysplasia
These are large and hyperechogenic kidneys, including renal ciliopathies. These conditions may be divided into autosomal dominant diseases and autosomal recessive disorders, including the polycystic kidney disease, renal dysplasia, glomerulocystic kidney disease (trisomy 13 and trisomy 18, Beemer syndrome), multicystic dysplastic kidneys (MCDK), medullary cystic dysplasia (Meckel-Gruber and Beckwith-Wiedemann syndromes, as well as congenital infections) [10, 11, 12, 13].
Nowadays, the fetal bladder and kidneys may be visualized starting with 11 weeks (by transvaginal echography) or 12 weeks (by means of transabdominal echography). The fetal bladder and kidneys are located near the spine, having an elliptical shape [1, 2].
In the first trimester of pregnancy, the kidneys appear as an ovoid structure located on both sides of the spine (Figure 1) [1, 2, 3, 4].
Fetal kidneys in the first trimester of pregnancy.
Renal urine production begins during week 9 of embryonic life, making it possible to visualize the bladder, as a fluid collection in the fetal pelvis. The bladder appears spherical and transonic and is located between the iliac bone centers of ossification, in the lower pelvis. It can be visualized starting with the ninth week of pregnancy, and the umbilical arteries can be visualized laterally next to the bladder. Beyond the first trimester, the bladder will fill and empty in an intermittent manner, every 25–30 minutes, due to the influence of hormonal factors on the bladder (Figure 2) [2, 3].
The bladder in the first trimester of pregnancy.
Normal ureters cannot be visualized by means of echography. The ratio of renal circumference to abdominal circumference is 0.27–0.30 and remains constant during pregnancy [8].
Evaluation of the urinary tract also requires the evaluation of the amniotic fluid volume. After the 14th week of intrauterine life, the amniotic fluid comes mainly from the production of fetal urine and only one-third of its quantity comes from the pulmonary fluid [2, 5].
For a correct diagnosis, the clinician has to perform a complete examination in all of the three planes, the coronal, the sagittal and the longitudinal plane, using 2D grayscale and color Doppler. The examination should be complete. Sometimes, the ultrasound examination has to be completed by another screening method. Due to the association between renal malformations and other congenital defects or chromosomal anomalies, performing an invasive diagnosis method may be required [14].
The renal pelvic dilatation (RPD) is the most common of the abnormalities that can be detected during antenatal ultrasonography and is probably the most frequent sign of a reno-urinary anomaly. The diagnosis of the RPD is based on an increased anteroposterior diameter of the renal pelvis in the transverse plane, and the value allows classification: severe, moderate or mild RPD. Normal values of anteroposterior diameter of the kidney pelvis are up to 4 mm at week 16 of pregnancy, less than 7 mm at 28 weeks of pregnancy and less than 10 mm postnatal [15].
In many cases a transient dilatation occurs. This situation is caused by narrowing or natural folds of the urinary tract that may occur during the early stages of development. Transient dilatation is usually less than 6 mm in the second trimester and less than 8 mm in the third trimester. It usually resolves spontaneously or disappear postnatally [16].
Many authors concluded that for an accurate diagnosis, the assessment of the renal and urinary function may be performed by ultrasound [5, 6]. The following statements gained acceptance:
The amount of amniotic fluid is an indirect indicator of the kidney function.
The bladder filling indicates the normal functioning of at least one kidney.
The absence of the bladder filling may indicate renal agenesis and bilateral ureteral obstruction.
The bladder distension may hide a urethral reflux problem.
The ureteral dilatation may be caused by a lower obstruction of the inferior urinary tract.
The echogenicity of renal parenchyma cannot be considered for the renal function assessment.
The increasing rebound pressure in the renal artery may cause renal function [5, 6, 7, 8, 9, 10, 11, 12].
Uropathies are the most common reno-urinary abnormalities diagnosed during the prenatal period and may be caused by obstructive or nonobstructive factors [10, 11, 12, 13]. The most common urinary malformations encountered in children are vesicoureteral reflux (VUR), obstructive megaureter, posterior urethral valve and megacystis [11].
Fetal hydronephrosis may result in a number of conditions, like pelvic or vesicoureteral junction obstruction, posterior urethral valves, vesicoureteral reflux, pelvic-ureteric junction obstruction and other rare congenital anomalies [12, 13]. A clear definition of hydronephrosis would be that it is a dilatation of the calyces and the renal pelvis of over 10 mm or more than 50% of the anteroposterior diameter of the kidney. This dilatation of the urinary system may occur at the upper urethral segment, ureters, bladder or kidney pelvis. Pyelectasis is the dilatation of the renal pelvis only (Figure 3) [6, 15].
Second trimester: different aspects in hydronephrosis cases.
By some authors, the clinician can diagnose hydronephrosis if the renal pelvic AP diameter is increased over 4 mm in the second trimester and 7 mm in the third trimester [3, 11, 15] (Figure 4). A renal pelvic AP diameter > 15 mm is strongly associated with a pathology of the urinary tract that requires treatment after birth. However, in the majority of cases, the renal pelvis is mildly or moderately dilated, and no cause is identified [16].
Hydronephrosis in the third trimester of pregnancy.
There is no clear consensus on the follow-up and management of mild or moderate hydronephrosis observed on antenatal ultrasound, although it is generally accepted that a postnatal assessment should be performed if the AP diameter of the renal pelvis exceeds 10 mm at any point in gestation [17].
Many studies show that a right or left prenatal AP renal pelvic diameter > 4 mm is associated with a higher risk of postnatal hydronephrosis compared with a right and left prenatal AP renal pelvic diameter ≤ 4 mm [15, 16]. Male neonates have a higher risk of postnatal hydronephrosis than females. These results can assist in establishing the appropriate follow-up method and evaluation of fetuses with renal pelvic dilatation [18, 19].
In medical practice many abnormalities can occur, like:
Number abnormalities
Structure abnormalities
Calibration abnormalities
Vesicoureteral reflux (VUR)
Abnormalities of the pyeloureteral junction
Ureteral abnormalities
Ureteral agenesis is accompanied by the absence of the ipsilateral kidney. It may be uni- or bilateral, the latter being incompatible with life.
Incomplete ureteral duplication (ureter fissus or ureter bifid)—a double-sided pyeloureteral system: the ureters bend before opening into the bladder through a single orifice.
Complete ureteral duplication (duplex ureter)—a double-sided pyeloureteral collection system: the ureters open through separate boreholes in the bladder, one in orthoposition and the other in the ectopic position (Figure 5) [15, 16, 17].
The ureteropelvic junction obstruction
Obstruction of the ureterobladder junction (obstructive megaureter) or obstruction on pyeloureteral junction is one of the most common causes of hydronephrosis found in children, its incidence being 1 case in 1000–2000 newborns. In this situation, hydronephrosis may be caused by an abnormal shape of the ureteral junction—the existence of the ureteral valves and the mucosal fold at this level. Like many other abnormalities, this pathology occurs much more frequently in males, usually unilaterally and especially on the left side [10, 14].
The ultrasound diagnosis is based on the observation of the increase of the anteroposterior diameter of the kidney, a degree of kidney pyelectasis. If the obstruction is unilateral and the filling of the bladder is normal, the normal amount of amniotic fluid will be preserved. When the damage is bilateral, the oligoamnios/oligohydramnios may appear.
In most cases this condition does not produce symptoms after birth; in 10–15% of the cases, it regresses spontaneously, but sometimes repeated evaluation is needed [1, 2, 3, 4, 5, 6, 7, 8].
Obstruction of the ureterobladder junction
This condition is the cause of approximately 5–10% of all cases of dilatation of the urinary tract. Ultrasound diagnosis is based on dilated urethra, with renal pelvis dilatation and normal bladder image. The cause of the disease is the dysfunction of the lower ureter, the outcome is favorable and the pathologic aspects disappear postnatally in many cases [16] (Figure 6).
The normal ureter size in children is up to 5 mm. Normal ureter cannot be detected during prenatal ultrasound examination. It can only be detected if it is dilated to a size greater than 7 mm and is observed like a translucent structure. The dilated ureter should be differentiated from full intestinal loops. Pathological dilatation of the ureter is more common in male patients, usually appearing to be unilateral (Figure 7) [15, 16, 17].
The dilatation of the ureter may be partial or total, and this pathology can be classified into the following conditions:
Obstructive-type megaureter
Reflux-type megaureter
Megaureter without reflux and without obstruction
Obstructive- and reflux-type megaureter
Vesicoureteral reflux
Vesicoureteral reflux (VUR) is characterized by the return of urine from the bladder to the kidney which often causes hydronephrosis and sometimes even abnormalities in kidney development (renal dysplasia). Causes include transient obstruction of bladder discharge, delayed maturation of the vesicoureteral junction and high bladder evacuation pressure. Patients with vesicoureteral reflux have a high risk of pyelonephritis, hypertension and progressive renal failure. Vesicoureteral reflux is represented by the retrograde passage of urine from the bladder to the ureter and subsequently to the kidneys, due to the incompetence of antireflux mechanisms [17, 19, 20].
This condition is usually easy to diagnose prenatally, when visualizing renal pelvis and calyces dilatations that vary in size, associated with unilateral or bilateral ureteral dilatations. RVU reveals a nonprogressive hydronephrosis with normal amniotic fluid index [10, 11, 12, 13, 18].
VUR classification:
Grade I reflux: reflux is only present in the ureter that has various degrees of dilatation.
Grade II reflux: reflux reaches the renal pelvis, without dilatation of the collector system, the papillae being normal.
Grade III reflux: moderate dilatation of the ureter, with or without sinusitis; moderate dilatation of the collector system.
Grade IV reflux: moderate dilatation of the ureter with or without sinuosity; moderate dilatation of the collector system; calyces are flattened but with the impression of the papilla still visible.
Grade V reflux: severe dilatation with ureter sinuosity and marked dilatation of the collector system; reflux in the parenchyma, with parenchymal thinning [10, 11, 12, 13, 14, 15, 18].
The prognosis is good. The prenatal diagnosis is important. Forty percent of the newborns develop severe kidney damage [2].
Ureterocele
As many other kidney abnormalities, ureterocele is more common in male patients. This pathology appears as a thin wall cyst or sept on the bladder wall [1, 16]. In many cases the diagnosis may be omitted when the bladder is full, the filling masking the cyst. There have been described cases of ureterocele shed in the urethra. This phenomenon may lead to acute obstruction of the lower urinary tract [1, 2]. The prognosis is favorable, but its evolution must be assessed postnatally, by residual renal function testing and reflux tests (Figure 8) [20].
Coronal section and high-definition power color Doppler, in a supernumerary kidney cases. Visualization of the double renal artery.
Contralateral pyelectasis in a unilateral MCDK case.
(a) First trimester: both renal arteries visualized in color Doppler, normal kidney images on both sides of the cross section and a kidney highlighted in the coronal section. (b) Second trimester (same case): asymmetrical bilateral pyelectasis, left kidney longitudinal diameter and hydroureter on the right side.
Ureterocele and hydroureter.
The bladder is a very important element in antenatal fetal examination. Clinicians may suspect anomalies of the bladder when not visualized on prenatal examination or when enlarged. From the pathological point of view, we may encounter various anomalies as well:
Megacystis is a neurodysplastic disease, due to the anomaly of innervation. This leads to bladder dilatation (over 7 cm in diameter). It may be associated with small, short and dilated bowels, as well as a low-caliber colon. At ultrasound, the striking signs are polyhydramnios, enlarged ureters and kidneys [17].
Congenital bladder diverticulitis. A septum can be observed.
Bladder exstrophy. It is commonly associated with other urogenital malformations and is constantly accompanied by epispadias. This pathology is characterized by many anomalies and lesions, such as:
Abdominal anterior wall injuries: inguinal hernia is common.
Lesion of pelvic bones: shortening and defects of rotation of pubic bones.
Lesions of the genitalia: micropenis and cryptorchidism appear in boys; in girls, the vagina is short and has various degrees of stenosis, the clitoris is bifid and the small labia are divergent.
The anterior bladder wall is absent, and the posterior wall is the submuscular segment of the anterior abdominal wall.
The bladder mucosa is exposed to the external environment, with the ureteric holes and the inner urethra opening visible.
Vesicoureteral reflux is present in all cases.
Some patients have rectal prolapse and anal incontinence; this phenomenon is due to the malposition of sphincter structures [1, 2, 3, 4, 15, 16, 17, 19, 20].
The most common obstructive cause of the lower urinary tract is the posterior urethral valve (PUV). PUV is due to the existence of membranes in the posterior urethra. Echography shows dilated bladder and urethral dilatation, giving a classic echographic sign—‘the keyhole sign’. Dystriation of ureters and troughs also occurs [14]. In advanced forms, oligohydramnios-associated pulmonary hypoplasia and urinary ascites may also appear. These fetuses require prenatal intervention to avoid kidney damage. Some authors tried to demonstrate that creating a vesicoamniotic passage may lead to a better outcome, but this has not yet been fully demonstrated [16].
In the prenatal life, other malformations may be seen:
Urethral agenesis (absence of urethra) is a rare malformation, incompatible with life unless an alternative communication between the bladder and amniotic sac exists. The urine is discharged through abnormal communication with other organs (between bladder and bowels or by umbilical fistula).
Congenital structures.
Rear urethral valves: mucosal lining located in the posterior urethra originating from the seminal colonic and insertion on the anterior wall of the urethra [14, 15, 16, 17].
Epispadias: abnormality characterized by opening the urethra on the dorsal face of the penis at variable distance of the gland, dorsal curvature of the penis and foreskin abnormalities. There are many forms of epispadias:
Balanic: distal incomplete defect.
Penian: incomplete proximal defect.
Penopubian: a complete defect, often associated with bladder exstrophy. In this situation, a distinct pathological condition appears: the exstrophy-epispadias complex [19].
Hypospadias: the anomaly is characterized by opening the urethra on the ventral side of the penis, at any level between the gland and the perineum, causing a ventral penis (chord). Patients with hypospadias have often abnormalities of the foreskin and cryptorchidic scrotum, inguinal hernia and hydrocele. Studies have shown a higher presence of hypospadias in patients with fetal growth restriction (Figures 9 and 10) [19]
Isolated megacystis: the right-side image is the sagittal plane of the fetus and the CRL (crown-rump length) measurement; the left-side image (same case) is the pathological specimen after medical termination of pregnancy.
Grade III hypospadias (perineal) is the most severe form, with the opening of the urethra at the penoscrotal junction.
The diagnosis of hypospadias with prenatal ultrasound is based on several important criteria:
A blunter bulbous tip to the penile shaft rather than the normal.
A ‘tulip’ sign formed by the ventral-bent penis located between the two scrotal folds.
Abnormal curvature of the penis.
A short penile shaft.
Ventral deflection of the urinary stream which can be studied by color Doppler [20].
Renal pelvic dilatation is commonly seen during antenatal ultrasound examinations, and its management remains a clinical dilemma. Although it is proven that severe antenatal hydronephrosis requires postnatal clinical and ultrasound evaluation, there is no consensus on the follow-up and management of mild or moderate hydronephrosis observed during antenatal ultrasound examinations [15]. The prenatal diagnosis may improve the prognosis and the outcome of the fetus. An early diagnosis and treatment of urinary obstruction may prevent the renal damage or loss of renal function [5, 21].
Most of the cases will spontaneously resolve after delivery. Thus, some assurance should be given. Many studies suggest follow-up when the AP diameter is 4–7 mm and antibiotic therapy when the AP diameter is greater than 7 mm [14, 18].
The postnatal assessment of fetal hydronephrosis may be invasive and lengthy [6, 7, 8]. Thus, the risks and the inconvenience of a protracted evaluation need to be weighed against the probability that milder degrees of renal pelvic dilatation will decrease without resulting in any renal damage [17].
The spectrum of congenital genital malformation is very broad, and the diagnosis is usually difficult. A reliable classification reveals four main types of genital anomalies:
True hermaphroditism: an individual has both ovarian and testicular tissues.
Male pseudohermaphroditism.
Female pseudohermaphroditism: adrenogenital syndrome or congenital adrenal hyperplasia. The main feature is clitoris hypertrophy.
Fetal gender abnormality is diagnosed by ultrasound or by finding a discrepancy between fetal phenotype and sex chromosomes. The ultrasound diagnosis is late, usually accessible in the second or third trimesters [5, 20, 21, 22, 23, 24].
Male genital malformations
Due to improved ultrasound technology and increased experience in this area, the fetal sex can be established with high accuracy beyond 13 weeks of pregnancy [5]. Determination of fetal sex is based on the ‘sagittal sign’. During the first trimester, in the sagittal plane, the penis is oriented upwards and the clitoris downwards. In the third trimester, the genitalia can be described with high accuracy [21].
Penian malformations (abnormal phallic structure)
Testicular malformations.
Number abnormalities
Anorchia (or anorchism): the absence of both testicles in the presence of a normal male phenotype (46XY)
Monorchism (or monorchidism): the absence of a testicle
Polyorchism: the presence of more than two testicles
Testicular fusion: the fusion of the two testicles in the same scrotum [2, 5, 20, 21, 22, 23, 24]
Development abnormalities
Microorchidism: small, hypoplastic testicles.
Macroorchidism may be secondary to contralateral testicular damage and may be bilateral in congenital syndromes (fragile X syndrome) or other disorders (hypophysis adenoma, aromatase deficiency).
Cystic dysplasia of the testicle: benign, congenital tumor, frequently associated with other testicular malformations [5, 20, 21, 22, 23, 24].
Migration abnormalities
Hypospadias: the left-side image is the ‘tulip sign’ in 2D conventional ultrasound; the right-side image is a 3D reconstruction, surface rendering technique.
Classification:
Intraabdominal: above or at the internal inguinal opening
Intracanalicular: in the inguinal canal, between the inguinal inlet and the external groove
Extracanalicular:
Suprapubian: just above the external inguinal opening above the pubic symphysis level
Infrapubian: in retroscrotal space, inferior to pubic symphysis [1, 5] (Figure 12)
Ectopic testis: migration is normal to the level of the inguinal external hole, but the testicle follows an abnormal tract. Possible localizations are between aponeurosis of external oblique muscle and subcutaneous or femoral, etc. [24].
Unilateral cryptorchidism (in association with penian anomaly).
It is recommended that information about the fetal abnormalities, postnatal and prenatal options of treatment and prognosis should be presented to the parents by a multidisciplinary team that includes neonatologists, urologists, perinatologists and medical geneticists with expertise in this field [5].
Ovarian cysts are the most frequently abdominal tumors that may be seen in female fetuses and newborns. The incidence of fetal ovarian cysts has increased lately, due to the improvement of ultrasound technology and due to the increase in the incidence of pregnancies that require hormonal treatment during the gestation period [2].
These ovarian tumors may be uni- or bilateral, sometimes multiple, and their appearance is as anechoic structures, thin-walled and having various sizes [5, 21, 22, 23, 24]. Some authors described cases with solid tumors, teratomas or hemorrhagic cysts. To increase the accuracy of the diagnosis, MRI examination may be required (magnetic resonance imaging (MRI)) [22].
Fetal ovarian cysts have usually a good outcome; most of them progress to spontaneous resolution in the postnatal period. The most frequent complication of cysts is ovarian torsion. Other complications may be intracystic hemorrhage, rupture, dystocia during birth, etc. There are no guidelines for monitoring and treatment of this condition. The non-invasive monitoring by ultrasound seems to be the best approach in prenatal life [1, 5, 19, 20, 21, 22, 23, 24, 25] (Figure 13).
Fetal ovarian cyst: 2D and 3D surface rendering images. The evolution of the case led to the typical ‘fluid–fluid’ level aspect, due to the intracystic hemorrhage.
Hydrocolpos is the accumulation of fluid in the vagina. When the fluid is observed on the vagina and the uterine body, the condition is called hydrometrocolpos. These diseases are caused by the persistence of the urogenital sinus or cloaca malformations [23]. The presence of a cystic mass in the presacral area, containing an anechoic fluid (suggesting urine) or sediment content, should guide the clinician to a diagnosis of urogenital sinus persistence [1, 2, 25].
The ultrasound diagnosis of renal and urinary tract abnormalities is generally based on the exclusion criteria, by comparison with the normal imaging one. In most cases, kidney or urinary tract abnormalities are diagnosed considering the appearance of amniotic fluid abnormalities, visualization of kidney size abnormalities or dilated appearance of the urinary tract. Congenital kidney abnormalities are often associated with the urinary tract malformation, and there is a wide range of anomalies resulting from disorders in the development process. It is important to differentiate abnormalities incompatible with life (as they require interruption of pregnancy) and asymptomatic/paucisymptomatic diseases in the postnatal life.
The genitalia anomalies must be treated by a multidisciplinary team that includes neonatologists, endocrinologists, urologists, perinatologists and medical geneticists with expertise in this field.
We have no conflict of interest.
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",metaTitle:"Refund Policy",metaDescription:"IntechOpen will act in accordance with its Refund Policy if requests for refunds are made.",metaKeywords:null,canonicalURL:"/page/refund-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"Refunds are possible in the following cases:
\\n\\n1. A double payment, in which case a full refund will be made.
\\n\\n2. A justified withdrawal of work by the Author, which had already been accepted during or after production but prior to publication. In this situation, a 50% refund will be made. (IntechOpen reserves the right to determine, at its discretion, whether withdrawal is justified and, consequently, whether a refund should be issued).
\\n\\n3. In those rare instances where IntechOpen declines to publish a book that had been previously accepted, full refunds will be made to the same account or credit card from which the Author made the original payment.
\\n\\nPlease note that refunded amounts will not always be exactly the same as original payment amounts due to bank transaction fees and expenses. Any such costs will be split evenly between IntechOpen and the Author.
\\n"}]'},components:[{type:"htmlEditorComponent",content:"Refunds are possible in the following cases:
\n\n1. A double payment, in which case a full refund will be made.
\n\n2. A justified withdrawal of work by the Author, which had already been accepted during or after production but prior to publication. In this situation, a 50% refund will be made. (IntechOpen reserves the right to determine, at its discretion, whether withdrawal is justified and, consequently, whether a refund should be issued).
\n\n3. In those rare instances where IntechOpen declines to publish a book that had been previously accepted, full refunds will be made to the same account or credit card from which the Author made the original payment.
\n\nPlease note that refunded amounts will not always be exactly the same as original payment amounts due to bank transaction fees and expenses. Any such costs will be split evenly between IntechOpen and the Author.
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