**20. Nephrotic syndrome**

Nephrotic syndrome is a known condition which increases the tendency to thrombosis [71, 72]. Although the mechanism of the tendency to thrombosis is not completely known, it is thought that lipid abnormalities increase the tendency to thrombosis by increasing haemoconcentration and hypervolemia and the viscosity of full blood and plasma and that hypoalbuminemia stimulates the synthesis of fibronectin, fibrinogen and factors II, V, X, XI, from the liver [73].

**23. Treatment**

suspected MI [10, 23].

**24.1. Alteplase**

**24. Fibrinolytic treatment**

tion of high-dose tPA [81].

intravenous thrombus cases [83–86].

As there are no comprehensive studies related to PMI treatment, the treatment principles of adult MI treatments have been adapted for children and have been formed from experience focussed on cases. Treatment must be organised according to the aetiology and clinical status of the patient. To determine arrhythmia or for early intervention when it has been determined, ECG monitorisation should be applied as soon as possible to all patients with

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In recent years, alteplase has become the most widely used fibrinolytic drug in children. The most important reasons for selection are that the half-life is short (approximately 5 mins), it is not antigenic and the effect is fibrin-specific [78]. It is a recombinant tissue plasminogen activator. In literature, there is no standard application related to r-tPA dosage in Paediatric patients. There are different applications in different centres. Nakagawa et al. applied intracoronary tPA at the dose of 200,000 unit/kg (0.34 mg/kg) to a patient with Kawasaki disease who suffered MI, but the patient died [79]. Subsequently, doses of 400,000 unit/kg (0.69 mg/ kg) and 800,000 unit/kg (1.38 mg/kg) intra-coronary tPA were applied to 2 other patients with Kawasaki disease who suffered MI, and the thrombi and cliinical findings of the patients were determined to have recovered without any complications. In addition to the tPA, Nakagawa et al. also administered urokinase infusion to the first and third of these three patients. Tsubata et al. applied a dose of 300,000 unit/kg tPA to an MI patient with Kawasaki disease as 10% of the total dose in bolus form and the remainder with a 1-hour infusion [80]. After 2 days, a dose of 50,000 unit/kg tPA was administered intra -coronary, but only a partial response was obtained in the thrombus. Krendal et al. treated a 7-year old Kawasaki patient with MI with intravenous 700,000 unit/kg tPA and a response was obtained clinically on echo. The success in that case compared to Tsubata et al. was associated with the administra-

In cases of intracardiac thrombus and intravascular thrombose**s,** while some centres have used 0.05–0.5 mg/kg/hr. infusion after 0.3–0.6 mg/kg bolus, other centres have administered infusion of 0.01–0.5 mg/kg/hr. without any loading dose, until the thrombus is resolved (max 96 hrs). This has been used and successful results have been obtained in Paediatric cases, especially in the opening of a central venous catheter and in intracardiac or intra-arterial and

After a loading dose of 0.1 mg/kg/10 mins in neonatal infants, some centres have administered maintenance at 0.3 mg/kg/hr. while others have given a loading dose of 0.7 mg/kg in 30—60 mins followed by 0.2 mg/kg/hr. As the infusion time extends, so the possibility of complications developing increases [82, 83]. Major complications that can develop are intracranial bleeding, epistaxis, melena and hematuria and minor complications may be seen as mucosal bleeding or bleeding from the needle entry site. Therefore, patients must be closely


**3. Accreditation Standards**

The accreditation standards used in biomedical calibration measurements can be classified into 2 groups. TS EN ISO / IEC 17025 and TS EN ISO / IEC 17020. While the standard of 17025 is used for the accreditation of testing and calibration laboratories, the standard of 17020 is used for the accreditation of inspection bodies.

The laboratory accreditation standards should not be confused with ISO 9001 standard. ISO 9001 is widely used in the assessment of the quality systems of production and service or‐ ganizations. Certification of organizations according to the ISO 9001 system expresses the compliance of that organization's quality system with this standard (ISO 9001). When certi‐ fying laboratories according to ISO 9001, this certification makes no statement on the techni‐ cal competence of laboratories. From this point, the certificate's power to convince the market and prospects of laboratories is quiet insufficient.

### **3.1. The standard of TS EN ISO / IEC 17025**

**•** the development and operation of Proficiency Testing schemes (Part 1)

**•** guidance on statistical methods (Annex A) and

schemes (Annex B)

84 Practical Concepts of Quality Control

**•** the selection and the use of schemes by laboratory accreditation bodies (Part 2)

**•** guidelines for development of a quality manual for the operation of Proficiency Testing

The statistical annex led to the development of ILAC Guide 13. ILAC G13 contains the techni‐ cal guidelines from Guide 43-1 expressed as requirements and includes the quality manage‐ ment system requirements from ISO/IEC Guide 25. Since G13 has management system requirements that are consistent with ISO/IEC 17025, Proficiency Testing providers accredited to this document are considered to be in conformity with the requirements of ISO 9001:2000 (Tholen, 2007). The standard ISO/IEC 17043 describes the criteria concerning the quality to be respected when developing proficiency tests and the use that can be made of these tests by the accreditation bodies. ILAC-G13 is useful to organizers for competence (Fraville et al., 2010).

The Proficiency Testing programmes of many Proficiency Testing providers around the world are now accredited by their national accreditation bodies, normally against the above documents. However, not all countries are ready to accredit Proficiency Testing providers,

Proficiency Testing programmes are operated by a variety of organizations within Europe and the rest of the world. Many Proficiency Testing programmes are international. There is a database of available Proficiency Testing programmes. In selecting the most appropriate Proficiency Testing it is important to consider a number of issues in order to judge its suita‐

The accreditation standards used in biomedical calibration measurements can be classified into 2 groups. TS EN ISO / IEC 17025 and TS EN ISO / IEC 17020. While the standard of 17025 is used for the accreditation of testing and calibration laboratories, the standard of

The laboratory accreditation standards should not be confused with ISO 9001 standard. ISO 9001 is widely used in the assessment of the quality systems of production and service or‐ ganizations. Certification of organizations according to the ISO 9001 system expresses the compliance of that organization's quality system with this standard (ISO 9001). When certi‐ fying laboratories according to ISO 9001, this certification makes no statement on the techni‐ cal competence of laboratories. From this point, the certificate's power to convince the

and not all Proficiency Testing providers wish to be accredited.

bility for your purpose (ISO Guide 34, 2000; ISO Guide 43, 1997).

17020 is used for the accreditation of inspection bodies.

market and prospects of laboratories is quiet insufficient.

**3. Accreditation Standards**

ISO IEC 17025, entitled "General Requirements for the Competence of Testing and Calibra‐ tion Laboratories", is an international standard describing the general requirements to meet for the recognition of that a laboratory is competent to perform specific tests (ISO IEC 17025; 2005). This international standard is used to develop the quality, management and technical systems of laboratories (Abdel-Fatah, 2010; Glavic-Cindro et al., 2006; Brantner et al., 2011; Zapata-Garcia et al., 2007; Jerone et al., 2008). Technical requirements are updated to include the addition of formal personnel training plans and detailed records, method development and validation procedures, measurement of method uncertainty, and a defined equipment calibration and maintenance program (Honsa et al., 2003). ISO 17025 certification can be ap‐ plied to all organizations that give services of testing or calibration. These organizations are the first-party, second-party and third-party laboratories.

First–party Laboratories: Manufacturer Laboratories, Second-party Laboratories: Customer Laboratories, Third-party Laboratories: Independent Laboratories.

This standard can be applied to all laboratories regardless of the scope of test or calibration activities and the number of personnel.

If testing and calibration laboratories comply with the requirements of this standard, a qual‐ ity management system to meet the principles of ISO 9001 will be also applied. There is a cross-match among TS EN ISO 17025 standard and ISO 9001. TS EN ISO 17025 standard cov‐ ers technical competence requirements, not covered by ISO 9001.

#### *3.1.1. The content of the standard of TS EN ISO / IEC 17025*

TS EN ISO 17025 standard is assessed in two main categories. The standard of TS EN ISO IEC 17025 contains both the management and technical requirements. In standard, 4th item describes the management system and 5th item describes the technical activities. The con‐ tent of 17025 standard is as follows:

0 Introduction

1 Scope

*Type B:* Inspection services should be given to the organization that consists of the inspection

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87

*Type C:* This type of bodies give services to both the organization that consists of the inspec‐

TS EN ISO 17020 standard can be applied regardless of the scope of inspection activities in the company. TS EN ISO 17020 certification can be given all kinds of inspection bodies that

In the standard of TS EN ISO IEC 17020, the technical requirements are the main aspect. TS

As it was mentioned earlier, there are 3 accreditation types for biomedical calibration meas‐

body. Type B bodies can not service to other organizations.

are willing to give service in accordance with this standard.

*3.2.1. The content of the standard of TS EN ISO / IEC 17020*

EN ISO 17020 standard consists of 16 items. They are:

4 Independence, impartiality and integrity

6 Organization and management

10 Inspection methods and procedures 11 Samples and materials to be inspected

14 The use of subcontractors 15 Complaints and appeals

**4. Accreditation Types**

**•** Calibration laboratories

13 Inspection reports and inspection certificates

tion body and other organizations.

0 Introduction

2 Definitions

3 Administrative Rules

1 Scope

5 Privacy

7 Quality System

8 Personnel 9 Equipment

12 Records

16 Co-operation

urements. They are:

The laboratory must be an institution that can be held legally responsible. Laboratory man‐ agement system must consist of facilities in fixed laboratory and temporary or mobile facili‐ ties that are linked to the laboratory.

#### **3.2. The standard of TS EN ISO / IEC 17020**

ISO 17020, entitled "General Criteria for the Operation of Various Types of Bodies Perform‐ ing Inspection", is an internationally recognized standard for the competence of inspection bodies. Inspection parameters may include such aspects as the quantity, quality, safety, suit‐ ability, facilities or systems (ISO IEC 17020; 2004).

There are 3 types of inspection organizations. They are:

*Type A:* Inspection body must be independent. Both the inspection organization and its per‐ sonnel must not be related to the inspected materials. They must not be the material's de‐ signers, manufacturers, suppliers, installers, purchasers, owners or operators.

*Type B:* Inspection services should be given to the organization that consists of the inspection body. Type B bodies can not service to other organizations.

*Type C:* This type of bodies give services to both the organization that consists of the inspec‐ tion body and other organizations.

TS EN ISO 17020 standard can be applied regardless of the scope of inspection activities in the company. TS EN ISO 17020 certification can be given all kinds of inspection bodies that are willing to give service in accordance with this standard.

### *3.2.1. The content of the standard of TS EN ISO / IEC 17020*

In the standard of TS EN ISO IEC 17020, the technical requirements are the main aspect. TS EN ISO 17020 standard consists of 16 items. They are:

4.6 Purchasing of service and materials 4.7 Customer service 4.8 Complaints

4.9 Control of nonconforming testing and / or calibration work

5.3 Accommodation and environmental conditions

5.4 Test and calibration methods and method validation

5.9 Assuring the quality of test and calibration results

The laboratory must be an institution that can be held legally responsible. Laboratory man‐ agement system must consist of facilities in fixed laboratory and temporary or mobile facili‐

ISO 17020, entitled "General Criteria for the Operation of Various Types of Bodies Perform‐ ing Inspection", is an internationally recognized standard for the competence of inspection bodies. Inspection parameters may include such aspects as the quantity, quality, safety, suit‐

*Type A:* Inspection body must be independent. Both the inspection organization and its per‐ sonnel must not be related to the inspected materials. They must not be the material's de‐

signers, manufacturers, suppliers, installers, purchasers, owners or operators.

4.8 Complaints

86 Practical Concepts of Quality Control

4.10 Improvement 4.11 Corrective action 4.12 Preventive action 4.13 Control of records 4.14 Internal controls

4.15 Management reviews 5 Technical requirements

5.6 Measurement traceability

5.8 Calibration procedures

5.10 Reporting of the results

ties that are linked to the laboratory.

**3.2. The standard of TS EN ISO / IEC 17020**

ability, facilities or systems (ISO IEC 17020; 2004).

There are 3 types of inspection organizations. They are:

5.1 General 5.2 Personnel

5.5 Devices

5.7 Sampling


*Edited by Razvan Udroiu*

The aim of this book is to present the latest applications, trends, and developments of computer-aided technologies (CAx). Computer-aided technologies are the core of product lifecycle management (PLM) and human lifecycle management (HUM). This book has seven chapters, organized in two sections: "Computer-Aided Technologies in Engineering" and "Computer-Aided Technologies in Medicine." The first section treats the different aspects of PLM, including design, simulations and analysis, manufacturing, production planning, and quality assurance. In the second part of the book are presented CAx applications in medicine focused on clinical decision, diagnosis, and biosensor design. CAx plays a key role in a variety of engineering and medical applications, bringing a lot of benefits in product life cycle, extending and improving human life.

ISBN 978-953-51-2787-1

Computer-aided Technologies - Applications in Engineering and Medicine

Photo by Elen11 / iStock

## Computer-aided Technologies Applications in Engineering and Medicine

*Edited by Razvan Udroiu*


3. Theory of homeostasis

the brain. A minimum of homeostatic load will serve as a criterion for this state. Joint behavior of a huge variety of such systems generates to complex forms of awareness. The neural tissue concentrates within itself the ability to evaluate its own state and endeavor to survive. A single cell, neurons in particular, can live, learn, want, suffer, delight, and try to survive [1]. Exertion of neuronal metabolism, leading to protection and goal-directed behavior, is rather appropriate for the description of conscious actions. Purposeful behavior corresponds to conscious decision and resembles a kind of generalized "pursuit of life." To the outside observer, this is

The essence of subjective feeling, goals, and will is still the amazing mysteries. The establishment of the theory of systems regulating optimal constants of their own state gives hope for understanding the problem of subjectivity, as homeostasis is the key tool that supports the system alive. The emergence of self as a state separated from the external environment is probably a direct consequence of the vitality of living systems. Alive system should assess its own vitality, and the phenomenon of maintaining its life is impossible to distinguish from instrumental actions. Probably, life appears along with the ability of an individual to evaluate its own integrity and health, and the homeostatic protection is a material manifestation of the pursuit of life.

Maintenance of vital activity resembles a manifestation of the mystical "vital force," which prevents disorder and violates the laws of thermodynamics. Homeostatic activities are so

The appearance of self-dissatisfaction plays a crucial role in triggering homeostatic protection, especially in the emergence of aware decisions. Nevertheless, it is difficult to provide a formal definition for the subjective feelings of discomfort that coincide with the appearance of damage. The assessment of general parameters is qualitative and is guided by the "injure-repair" scale. Living systems somehow regulate the avoidance of injury and the aspiration to life as it shifts toward death or life, that is, behaves as an object possessing minimum awareness. This mysterious variable may not be a function of the state and should depend on the previous history of the system, since homeostasis, as well as behavior, improves after exercise [1].

We have no possibility of determining how a neuron evaluates its own state, but we know that injury decreases positive feelings, while protection decreases distress. In any case, the approach of death increases cellular efforts to operate. A living system reacts to damage as if it is having a negative sensation. Homeostasis entails a relationship between physiology and mind. The problems of consciousness and the problem of life self-maintenance are inseparable.

It is likely that the origin of life necessarily leads to the emergence of consciousness.

Theoretically, there are two explanations for homeostatic operation:

2. Spontaneous relaxation, which minimizes injury.

1. Rigid mechanistic programs that evaluate all options for possible injures.

rational that their discoverer, W. Cannon, described them as "Wisdom of the body."

reminiscent of intentional action and a manifestation of will.

2.3. Emergence of the feeling of a death threat

150 Lagrangian Mechanics

2.4. Homeostatic regulation


**1. Introduction**

The cytochrome P450 (CYP) superfamily is a group of Phase I mono-oxidase enzymes with broad substrate specificity that is responsible for the majority of xenobiotic metabolism [1]. CYP enzymes are also involved in vital endogenous pathways, including prostaglandin metabolism and steroid hormone biosynthesis [2]. Gene names are determined according to a standardized nomenclature. Using CYP3A4 as an example, "CYP" refers to the superfamily of cytochrome P450 genes, "3" refers to the family designation (<40% amino acid identity with other CYPs), "A" refers to the subfamily designation (40–55% amino acid identity with other CYPs in that family), and "4" refers to the specific gene within the subfamily with >55% sequence identity [3]. This enzyme superfamily is ubiquitous in nature—it is present in bacteria, fungi, plants, and animals—with varying expression patterns [4]. In fact, many drug metabolizing isoforms including CYP 1A, 2C, and 3A show significant interspecies differences in enzymatic activity while CYP 2E1 does not [5].

Hepatocytes express an abundance of drug metabolizing CYP enzymes and demonstrate the greatest capacity for Phase I xenobiotic biotransformation, followed by the small intestine and kidneys [6–8]. Of the 57 known human CYP enzymes, five CYP isoenzymes from CYP 1–3 families metabolize the majority of clinically used drugs—CYP3A4/5, CYP2D6, CYP2C9, CYP2C19, and CYP1A2 [9]. Although CYP 1–3 families predominantly aid in xenobiotic detoxification, CYP enzymes are also involved in the bioactivation of xenobiotics, resulting in the formation of toxic intermediates. CYPs 1B1, 1A1, and 2A6 are involved in the bioactivation pathways of cigarette smoke constituents [10,11], while CYP2E1 is involved in the metabolism of alcohol and acetaminophen [12]. These are associated with the generation of hepatotoxic or carcinogenic metabolites and promote reactive oxygen species (ROS) production in vitro and in vivo [13–15], which eventually causes organ damage and cancers.

CYP enzymes are generally upregulated by their own substrates/drugs, resulting in enhanced metabolism and suboptimal plasma concentrations of concurrent drugs [16]. Conversely, CYP inhibition by various drugs contributes to supratherapeutic drug levels and drug-induced toxicity, thus preventing CYPs from performing their protective role in detoxification [16]. In the case of prodrugs that require CYP-mediated conversion to their active form, the reverse is true. Prototypical pharmacologic CYP enzyme inducers and inhibitors that are commonly implicated in drug–drug interactions include rifampin (inducer) and azole antifungals (inhibitors), which may interact with multiple CYP isoenzymes to varying degrees [9]. Further, pharmacogenetic variations in CYP activity may result in reduced, absent or increased metabolic capacity. Drug metabolizing isoforms with functionally relevant polymorphisms include CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 [17,18]. Certain isoforms are more highly polymorphic than others [17] and are associated with clinically significant effects, such as toxicity or lack of therapeutic response [17]. Furthermore, while CYP enzymes are most abundantly expressed in the liver, they are also found in extrahepatic tissues throughout the body. Although the majority of extrahepatic CYPs are involved in endogenous pathways [2], drug metabolism also occurs outside the liver. The small intestine and kidneys are the primary sites of extrahepatic drug metabolizing CYP enzymes [6,7]; however, drug metabolizing CYPs are also expressed in the lungs, blood (monocytes, lymphocytes), brain, and heart [19–22]. Extrahepatic CYP enzymes contribute to cell-specific biotransformation, albeit to a lesser extent than hepatic CYPs. While extrahepatic CYP expression and metabolic capacity are not able to mediate total body clearance of xenobiotics, the enzymes may play a significant role in local tissue exposure and toxicity [19].

Recently, we provided the first evidence that functional CYP isoforms are packaged into extracellular vesicles (EVs) derived from human plasma of healthy volunteers, as well as in EVs derived from hepatic cell lines [23]. Extracellular vesicles (EVs) are nanosized, membrane-bound particles that are secreted from most cell types into biological fluids, namely plasma, and are taken up by other cells [24]. EV cargo includes a heterogeneous array of biomolecules, e.g., lipids, carbohydrates, cytokines, proteins, and nucleic acids—mRNAs, miRNAs, etc. [24–26]. Thus, EVs are thought to be critical in cell-to-cell signaling, protein transfer, and nucleic acid shuttling [24,27,28]. These characteristics suggest that EVs might be potential biomarkers, therapeutic targets, and drug-delivery systems [24].

It is important to note that exosomes are a subgroup of extracellular vesicles with a distinct biogenesis pathway [29]. Although much of the literature prior to 2018 refers to "exosomes", distinguishing exosomes from other EVs has proved challenging due to overlaps in size, composition, and marker proteins [30]. Therefore, in accordance with current ISEV guidelines [30], this review will exclusively refer to "EVs" even when published reports refer to "exosomes".

As drug metabolic capacity is limited in extrahepatic tissues, it is possible that CYP-containing plasma EVs are secreted from the liver, circulate via plasma, and are delivered to distant sites (e.g., brain cells), where they may aid in extrahepatic drug metabolism, detoxification, and may also influence toxicity at these sites (Figure 1). It is also possible that extrahepatic cells in the kidneys, lungs, blood, heart, and brain also secrete EVs that are pooled in the plasma and cerebral spinal fluid (CSF), making an "EV-depot". These EVs may then be delivered to other cells as needed and under specific

conditions, to perform biological functions. This review will provide an overview of the contribution of CYPs to drug metabolism in extrahepatic tissues. Since our primary goal is to discuss relevant drug-metabolizing CYP enzymes and their xenobiotic substrates, discussion pertaining to endogenous pathways is largely outside the scope of this review. Importantly, we will summarize the most recent literature pertaining to CYPs and EVs, the relative abundance of CYPs in human plasma-derived EVs, and potential implications of CYP-containing EVs in xenobiotic biotransformation/bioactivation. Further, we will discuss the potential role of EV CYP enzymes as biomarkers in various pathological conditions and xenobiotic exposure/drug use, as well as suggest novel therapeutic interventions.

**Figure 1.** Cytochrome P450 (CYP)-containing plasma extracellular vesicles (EVs)/exosomes are secreted from the liver and other peripheral organs, circulate via plasma, and are delivered to distant sites (e.g., brain cells), where they may aid in extrahepatic drug metabolism, detoxification, and may also influence toxicity at these sites. Similarly, secretion of EVs from extrahepatic cells, including brain cells are also likely to contain CYPs in addition to other biomolecules, which would also be circulated via plasma and delivered to other distant cells.


*5.1.7 Progressive complex alliances*

Progressive complex alliances (*center triangle*) represent a difficult to achieve form of stakeholder partnership that effectively balances the interests of rural communities and the private and public sectors. In many cases, the loans from development banks are focused on combined actions involving these stakeholders through their combined participation and investment, although formula for success remains ambiguous as it involves complex, knowledge-rich problem-solving across competing interests and site-specific settings.

#### **5.2 Sector interactions**

Successful partnership within rural development programs striving for agricultural transformation, particularly within the realm of progressive complex alliances, requires effective communications between sectors (**Figure 2**). Between farming communities and the public sector, these communications involve advocacy on behalf of agricultural producers and their workers, and effective response from agricultural extension services. This dual mechanism ensures that public investment in advisory services is demand-driven. Unfortunately, rural communities often find it difficult to express their needs, and those that do so on their behalf may behave opportunistically. At the same time, public agricultural extension services are too often understaffed and underresourced, yet it is this communication that can lead to more efficient performance by extension specialists and project designers.

Communication between farming communities and the private sector is more direct. Businesses stream input products through agrodealer networks to farming communities and later purchase their surpluses through buyers. Accompanying these input products is information about them that is intended to achieve or maintain various competitive advantages. Farmer feedback on the availability, efficacy, and affordability of these input products is mainly felt in terms of seasonal purchases. At the same time, businesses seek direct feedback from potential customers to guide their selection of product lines and advertising campaigns. One difficulty in this dual mechanism is the inability of poorer farmers to purchase the full suite of

**Figure 2.**

*Key interactions between the public, private, and farming sectors that relate to the design and implementation of rural development projects.*

recommended input products proven to maximize their production. There is also the risk that unless accompanying technologies are properly bundled, the returns to any one technology may be disappointing. This communication mechanism can lead to alliances between farmers and businesses in terms of bulk purchase of production inputs and better coordinated marketing of produce.

Interactions between the private and public sector are focused on regulatory approval of products and steering financial incentives, often in ways designed to maximize profits or taxation and that often bypass farming communities. Nonetheless, the opportunities for co-investment into modernizing technologies through these dealings are enormous and can lead to the formulation of needed public-private partnerships that indirectly benefit farmers. One risk of this dialog, however, is where haphazard or opportunistic privatization may result in parastatal inefficiencies being replaced with private sector excesses.

Clearly, the optimal situation is where tripartite communication leads to the design and successful implementation of rural development projects that engage and benefit all three parties: rural communities, the private sector, and government (**Figure 2**). These complex alliances require problem-solving with clear agreement of which difficulties exist, how to merge possible solutions within everyone's best interests, and how different options most appealing to those different interests may be blended or pursued simultaneously. From the programmatic perspective, it is also important to establish how resulting activities may be accurately and continuously monitored within the context of contingencies and corrective adjustment. This level of communication as it relates to the deployment of modernizing agricultural technologies in Africa has proven to be no easy matter.

*Blending Climate Action and Rural Development in Africa's Sahel DOI: http://dx.doi.org/10.5772/intechopen.103817*

**Figure 3.**

*Selected climate-smart technologies important to the Sahel as positioned within the Agricultural Transformation Triangle.*

#### **5.3 An example from the Sahel**

Technologies may be positioned within the agricultural transformation triangle assuming that the relative importance of the three different drivers can be assigned (**Figure 3**). This positioning is based on the relative importance of each driver in the deployment of technologies and development outcomes, recognizing that all of them must ultimately be acceptable to rural households to become widely adopted, whether as technology customers or management practitioners. This approach, applied to the 17 technologies appearing in **Table 1**, results in clusters of technologies including those that are mainly achieved through grassroots efforts (upper center), or by private sector investment (lower left). Note that the positioning of new cereal varieties depends largely on whether they are hybridized or open pollinated, as the latter allows for communitybased and farmers-own seed production. Also note that systems-level changes (e.g. containment of insect invasions, elimination of *Striga*, agroforestry parkland establishment) require greater involvement of the public sector. One advantage of this approach is that technologies appearing in different clusters and within realms (see **Figure 1**) can be considered mutual objectives within a program's operational framework.

### **6. Investment volumes**

Substantial if not ample investment in the agriculture of the Sahel occurs (**Table 5**). Researchers at the Policy Analysis and Research Group at of Evans

**Table 5.**

*Annual investment in African agriculture and natural resource management by three major International Financial Institutions: The African Development Bank, The World Bank, and the International Fund for Agricultural Development (based on EPAR1 ).*

School of Public Policy and Governance (University of Washington) recently compiled data from three major International Financial Institutions (The World Bank, the African Development Bank, and the International Fund for Agricultural Development) to provide insights into the "Investment Landscape" in Africa [40]. The database contains all investments in 46 sub-Saharan African countries from the three IFIs as of May 2021 and includes "active" or "implementation" projects, loans, grants, or other financial investments [40]. To make funding by country more comparable, investments were annualized by dividing the total financial commitment per project by the number of years of implementation. Codes were applied that allowed summation for Sahelian countries including Burkina Faso, Chad, Mali, Mauritania, Niger, Senegal, and South Sudan, but not those with a small portion falling within the Sahel (e.g. Benin, Cameroon, and Nigeria). Annual investment in agricultural development across all of sub-Saharan Africa totaled US \$6.24 billion in 2019, with 11% of it (=\$0.68 billion) directed to the Sahel. This amount is proportionate in terms of population (±0.3%) and represents 20.1% of total IFI investment. Considering the importance of agriculture in the Sahel, this percentage seems somewhat low.

Overall, the per capita annual investment from the three IFS in the Sahel zone is about \$30. What can be done with this resource and how may it best be leveraged toward greater benefit? **Table 3** suggests that the cost of modernizing Sahelian farming is about \$136 per ha, so these funds are only sufficient for improved production on only 0.22 ha on a household basis. This intervention results in an additional 288 kg food production and revenues worth \$73. These modest gains can lead to substantial improvement in lives. If 50% of the funds earmarked to smallholder agriculture in the Sahel (about \$295 million, calculated from **Table 5**) was directed to the delivery of TAAT cereal technologies, this is sufficient to "jump start" improved production across 2.17 million ha (calculated from **Tables 3** and **5**) resulting in 2.8 million additional tons of cereal and profits of over \$560 million per year from improved agriculture. A similar analysis may be performed based on funds directed to cultivated lands rather than households (**Table 5**). About \$16.30 per ha is invested by IFIs in the Sahel, considerably less than the average across sub-Saharan Africa. This level of

investment is sufficient to modernize production on 0.34 ha, producing about 445 kg of additional cereal, leading to a huge improvement in food security (calculated from **Tables 3** and **5**).

These same gains would lead to an estimated additional 3.3 million MT of sequestered CO2e across the Sahel worth \$71 million (calculated from **Table 4**), assuming that buyers for that offset due to climate adaptation can be found. One complication, however, is that the costs of directly quantifying carbon offsets on a smallholder farm may well be greater than the value of those offsets themselves (\$33 calculated from **Table 4**). Clearly, potential exists for combined agricultural development and climate action given the current level of development investment, and the challenge is to better realize these gains so that even more investment will follow.