FS2004 aircraft‐simulated characteristics PREADAR MQ‐1.
\r\n\tWhile histopathologically, the most common minimal change disease is focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, mesangial proliferation, proliferative glomerulonephritis, and membranous glomerulopathy can be seen. Treatment is planned according to symptoms, complications, and primary disease. The first goal is to minimize protein loss. Although corticosteroids are the first choice in treatment, if side effects occur or the disease does not respond, immunosuppressive treatments are applied. Current treatment approaches have shown promising results in terms of disease treatment. However, its long-term side effects and remission sustainability are still unclear.
\r\n\r\n\tNephrosis is an inflammatory, neoplastic or non-vascular nephropathy that causes degenerative changes and solute accumulation in tubules and glomeruli. Nephrosis may be due to a primary cause or secondary to another disorder. Nephrosis is often seen as amyloid nephrosis and osmotic nephrosis. Osmotic nephrosis causes structural changes with intracytoplasmic vacuolization and swelling of tubular cells, occurring primarily in the proximal tubules, without a change in osmotic balance, resulting from certain solutes such as dextran, contrast dyes, mannitol, and hydroxyethyl starch. It can lead to clinical manifestations ranging from acute renal failure to chronic kidney disease.
\r\n\tAmyloid light-chain amyloidosis is the most common type of amyloidosis, with the kidney one of the organs most commonly affected. With the enlargement of the kidney area affected by amyloid deposits, proteinuria and renal dysfunction are usually observed. This topic includes advances in research on the etiology and pathogenesis of nephritis, nephrotic syndrome, and nephrosis, new early diagnosis methods, follow-up and treatment plans, and case series. It will provide significant opportunities and support to scientists, philosophic and medical doctors, urologists, nephrologists, public health practitioners, and family physicians from around the world to share new research, ideas, and solutions.
In reality, all physical systems are affected by uncertainties due to modeling errors, parametric variation, and external disturbances. Controlling of dynamical systems in the presence of uncertainties is extremely difficult as the controller\'s performances degrade and the system may even be led to instability. As such, active researches are continuing to develop controllers that can work successfully in spite of uncertainties. Robust control techniques such as nonlinear adaptive control, model predictive control, backstepping and sliding mode control [1, 2, 3, 4, 5, 11, 19, 20, 32, 34] have been evolved to deal with uncertainties.
The classical Sliding Mode Control (SMC) leads, generally, to the appearing of an undesirable chattering phenomenon [2, 3, 9, 10, 13, 14, 15] to solve this problem we propose an approach using the Adaptive Integral High Order Sliding Mode Controller (AIHOSMC). This technique ensures a good tradeoff between error and robustness against noise and especially a good accuracy for a certain frequency range, regardless of the gain setting of the algorithm. This technique is based on estimating the successive derivatives of the sliding mode surface and transmitting them to the control block, all by using an aircraft in virtual simulated environments [24, 25]. It is real‐time virtual simulation, which is close to the real‐world situation.
The piloting technique proposed in this work is more robust and simpler to implement than the quaternion one. It only requires information about the sliding mode surface.
Through a methodology based on the confrontation of the real and the simulated worlds, the main objective of this chapter is to develop an autopilot based on a robust controller to maintain the desired trajectory (Figure 1).
Real trajectory.
To achieve this objective, we use the flight simulator FS2004 as a simulated world environment coupled to a hardware and a software development platform. This simulator is developed by Microsoft, with several simulated aircraft included in its airplane library. We choose the Predator MQ‐1 (Figure 2). It is considered as a reconnaissance and an intelligent system.
The predator MQ‐1 flying in FS‐2004.
In this work, the main goal is to maintain the desired aircraft\'s trajectory; and to do so, we propose the following approach:
description and analysis of the aircraft system model;
implementation of a real‐time interface between the flight simulator FS2004 and the module real‐time Windows target of Simulink/Matlab;
development and implementation of the piloting law based on adaptive integral sliding mode for the design of the autopilot controller;
flight tests.
The MQ‐1 predator is an American unmanned aerial vehicle (UAV) that can serve in the reconnaissance or attack role. Predator has been in the United States Air Force (USAF) service since 1995 and has seen combat in numerous theatres.
Airwrench tool gives access to flight dynamic characteristics (http://www.mudpond.org/AirWrench_main.htm). This tool allows creating and tuning flight dynamics files description of simulated planes models. This software uses aerodynamics formulas and equations described on the Mudpond Flight Dynamics Workbook. It calculates aerodynamic coefficients based on the physical characteristics and performance of the aircraft (Table 1).
Dimensions | Moments of inertia |
---|---|
Length: 11.88 m | Pitch: 1800.0 |
Wingspan: 14.84 m | Roll: 3700.00 |
Wing surface area: 11.43 m2 | Yaw: 1800.00 |
Wing root chord: 1.55 m | Cross: 0.00 |
Aspect ratio: 19.28 | |
Taper ratio: 0.10 |
FS2004 aircraft‐simulated characteristics PREADAR MQ‐1.
We communicate with FS2004 by using a dynamic link library called FSUIPC.dll (Flight Simulator Universal Inter‐Process Communication). This library created by Peter Dowson and is downloadable from his website [36] (
To read or write a variable using the FSUIPC, we need to know its offset address, its format, and the necessary conversions. For example, the bank angle (
Offset | Name | Var. type | Size (octet) | Usage |
---|---|---|---|---|
057C | Bank angle ( | S32 | 4 | Degree |
578 | Elevation angle ( | S32 | 4 | Degree |
580 | Head angle ( | U32 | 4 | Degree |
02BC | Speed IAS ( | S32 | 4 | Knot*128 |
0BB2 | Elevator deflection ( | S16 | 2 | -16383 to +16383 |
0BB6 | Aileron deflection ( | S16 | 2 | -16383 to +16383 |
0BBA | Rudder deflection ( | S16 | 2 | -16383 to +16383 |
088C | Thrust control ( | S16 | 2 | -16383 to +16383 |
Flight parameters in the buffer FSUIPC.
To deal with the design of an autopilot controller, we propose an environment framework based on a software in the loop (SIL) methodology (see Figure 3) and we use Microsoft flight simulator (MSFS‐2004) as a plane simulation environment [24, 25].
Software‐in‐the‐loop architecture.
This work is a real‐time virtual simulation, we read or/and write the desired parameters from and to MSFS‐2004 through the computer memory by using the FSUIPC library.
The model describing the system is presented by [12, 25, 26]
with is the aircraft state vector in the body frame:
We propose the following output vector:
The nonlinear functions
where,
where
The coefficients
Expression of the modified aerodynamic coefficients.
Consider the following nonlinear uncertain system [31]
The uncertainties in
The
is called “
With
With
Functions
The
With
Consider the following state feedback control
with
Applying Eq. (13) to system (10), one gets
The control objective is now the following: how to define a discontinuous control law ensuring the stabilization of the previous system, in a finite time and in spite of the uncertainties?
We proposed two high‐order sliding mode controllers based on integral sliding mode concept [27]: the first requires knowledge of the uncertainties bounds, whereas, for the second one, no knowledge of the bounds is required. This latter feature is due to an adaptation law for the control gain.
The following theorem proposes a continuous finite time stabilizing feedback controller for a chain of integrators, by giving an explicit construction involving a small parameter. One gets an asymptotically stable closed‐loop system; the system is homogeneous of negative degree with respect to a suitable dilation, which implies the finite time stability. Consider the system (12) with no uncertainty (
Let
With
For
Consider the following function, named “integral sliding variable,” defined as (
with the term
This latter feature is a key point of the integral sliding mode controller; in fact, the definition of the integral sliding variable allows to ensure that a sliding mode has been established early from the initial time, thanks to the finite time convergence property of
From the previous inequality, it is clear that, if the control
Then, in order to stabilize system (15), the following control law is defined
This controller has two parts:
The first one
The second one
ensures the establishment of a
The relative degrees are
The input control
We propose the integral sliding variable as follows:
where
In Theorem 1, we choose
The integrators’ chain is defined by
where,
The control input can be chosen as
where
The reduction of the noise is assumed by the presence of the linear term (
The dynamic adaptation of the gains
The application of this piloting technique in FS2004 is shown in Figure 2.
The input signals at the upper and lower saturation values of the control laws are used to respect the actuators bounds. Scaled functions are added to take into account the actuators resolutions.
The adaptive integral high‐order sliding mode technique is used to recover the desired signal. Several flight tests were realized to demonstrate the effectiveness of the combined controller/integrators’ chain.
We run the flight simulator FS2004 and the interface with the module real‐time windows target of Simulink/Matlab.
In a first step, we used aircraft predator, the aircraft taking off was done using the keyboard. Then, we run our software to transmit the control inputs based on the adaptive integral higher‐order sliding mode to the autopilot controller in order to maintain the desired trajectory.
The desired signal injected and the output integrators’ chain are shown in Figure 4. We notice the outputs of the integrators’ chain
Application of the adaptive integral high order sliding mode controller in FS2004.
Reference and output integrators.
Figure 6 shows the error between the output integrators’ chain
Surface sliding mode
The input signals at the upper and the lower saturation values of the aileron, rudder, and elevator deflections are used to respect the virtual Joystick (PPjoy) bounds. Upper limit: 62767, lower limit: 1.
Airwrench gives the following data:
Aileron parameters: Aileron area 1.70 m2, aileron up angle limit 20.0°, aileron down angle limit 15.0°.
Elevator parameters: Elevator area 1.54 m2, elevator up angle limit 25.00°, elevator down angle limit 20.00°.
Rudder parameters: Rudder area 0.62 m2, Rudder angle limit 24.00°.
The aileron, elevator, and rudder deflections are shown in Figures 7–9. We notice the absence of the chattering phenomenon.
Ailler control.
Rudder control.
Elevator control.
The evolution parameters
Dynamic parameters evolution
The flight tests demonstrate the robustness of the adaptive integral high‐order sliding mode. It makes it possible to ensure a better derivation of the desired input signal in real time, and this is to ensure a good accuracy of tracking the desired trajectory.
In this chapter, a procedure of the communication with an aircraft model in a simulated environment and the implementation of the real‐time interface between the Microsoft flight simulator and the module “real‐time windows target” of Simulink/Matlab has been presented. After that, an adaptive integral sliding mode for an aircraft autopilot has been presented. Our approach uses the environment simulator (FS2004) to reduce the design process complexity.
For the piloting part, we have interested the gain adaptation for the reduction of chattering phenomena and possibility to control the aircraft presented by the uncertain nonlinear systems in which the uncertainties have unknown bounds. This technique is more robust and simpler to implement than the quaternion one and only needs the information about the sliding mode surface.
The flight tests demonstrate the robustness of an adaptive integral sliding mode. The former ensures a better derivation of the desired input signal in real time, and this ensures a good accuracy in terms of tracking for a desired reference.
All surgical procedures, including dental surgery, present risk of complications, which may include pain, nerve injury, swelling, infections, and hemorrhage. Dental surgery is defined as any dental intervention including an incision in the oral mucosa or gingiva, including anything from a simple dental extraction to alveoloplasties [1]. Bleeding control is an important step during dental surgery procedures [2] because excessive bleeding complicates surgery and increases the risk of morbidity. To avoid such complications when long-lasting bleeding occurs, despite the proper use of traditional techniques for hemorrhage control, a broad range of hemostatic agents are available, as adjunctive measures to enhance hemostasis in the course of dental surgeries [3]. Despite the expressive rise in the amount and types of topical hemostats in the past decade, high-level evidence regarding the management of these agents during bleeding in dental surgery is still lacking.
\nThe periprocedual management of patients receiving therapeutic anticoagulation represents a challenge for dental practitioners, as the risk of bleeding must be counterbalanced against the risk of systemic or local thromboembolic phenomena. Recommendations for dental interventions in individuals receiving anticoagulation therapy remain quite unclear, in spite of practice guidelines from both dental [4] and medical [5] fields.
\nThis chapter aims to discuss the effective ways of managing bleeding complications in dental surgery, mainly in high-risk patients. The role of biosurgical materials to prevent or solve these complications, during and after dental surgery procedures, will also be addressed, as well as their modes of action, practical applications, adverse effects, and effectiveness.
\nThe physiological mechanism that prevents and hinders bleeding at the area of an injury while preserving regular blood flow everywhere else in the circulation is called hemostasis [6]. The hemostasis process has two major components. Primary hemostasis initiates promptly after vascular injury, and it can be divided into four consecutive and superposed stages: (A) vasoconstriction, (B) platelet adhesion, (C) platelet activation, and (D) platelet aggregation [7, 8, 9, 10]. Primary hemostasis results in the formation of a platelet plug [10]. Secondary hemostasis comprises a sequence of serine protease zymogens and their cofactors, which interact successively on phospholipid surfaces (damaged endothelial cells or platelets), leading to the development of covalently cross-linked fibrin [10, 11, 12]. This cross-linked fibrin mesh is then incorporated into and around the platelet plug. It strengthens and stabilizes the blood clot. These two processes are intertwined and occur at the same time [6]. These systems are regulated by multiple anticoagulant mechanisms, which are responsible for maintaining blood fluidity in the absence of injury, generating a clot that is consistent with the trauma. Hemostasis and the avoidance of bleeding or thrombosis are directly related to the adequate balance between procoagulant and anticoagulant systems [6].
\nHemorrhage in dental surgery can be categorized as:
Primary hemorrhage: bleeding occurs during surgery
Reactionary hemorrhage: bleeding occurs 2–3 hours after surgery
Secondary hemorrhage: bleeding occurs until 14 days after surgery, probably due to an infection
Hemorrhage can also be categorized according to the area injured: vascular, bone, and soft tissue [13, 14]. Bleeding diathesis is an unusual susceptibility to bleeding and may be genetic, autoimmune, or acquired (Table 1) [15, 17]. Selected bleeding disorders will be covered in this chapter.
\n\nThe most prevalent hereditary bleeding disorders are von Willebrand disease and hemophilia, affecting 1% of the population and 20,000 people in the USA, respectively [18, 19, 20, 21, 22]. Dental patients presenting inherited bleeding present a significantly higher risk of perioperative bleeding. The frequency and severity of bleeding are related to disease-related factors, such as the severity of the hemophilia. Factors related to the patient include the level of periodontal disease, vasculopathy or platelet dysfunction, and procedure-related factors (teeth extracted—type and the number—or the size of the wound area) [23].
\nOne example of autoimmune bleeding diathesis is the immune thrombocytopenic purpura (ITP), an idiopathic thrombocytopenic purpura condition, characterized by isolated thrombocytopenia without a clinically apparent cause [24].
\nThe most common acquired bleeding diathesis is the one related to hemostasis-altering medications. Anticoagulant agents are among the most prescribed medications in the USA [25]. For decades, anticoagulants have been prescribed to prevent arterial and venous thromboembolism [1]. Prolonged bleeding and bruising are some of the adverse events related with these medications [4]. The most frequently used drugs are therapeutic platelet inhibitors, vitamin K antagonists, or direct oral anticoagulants. Patients susceptible to hemorrhage may present severe bleeding resulting from dental surgery procedures. The use of biosurgical hemostatic agents to decrease or control bleeding may be beneficial for patients at risk for bleeding diathesis.
\nBleeding complications can occur either in healthy or systemically compromised patients. Some patients tend to bleed excessively during or after dental surgery, due to different factors, such as anticoagulant therapy, inherited bleeding disorders, uncontrolled hypertension, extreme trauma to soft tissues, and non-compliance to postoperative recommendations. In these cases, the use of an effective hemostatic agent enhances hemostasis, providing a wide spectrum of benefits, such as superior management of the anticoagulated patient, shorter operation time, as well as smaller wound exposure and shorter recovery time.
\nThe ideal topical hemostatic agent should be biocompatible, affordable, and effective [14, 26, 27]. In recent years, the number of different topical hemostatic agents has increased significantly (Table 2). Knowledge and familiarity with the wide range of topical hemostatic agents available are essential for dental practitioners, including their effectiveness, mode of action, and adverse effects. A well-informed professional will be able to opt for the most effective and practical agent for each situation. In relation to the use of local hemostatic in dental procedures, available scientific data is not homogenous. Most publications use one or more local hemostatic agents to compensate for the anticoagulant effect and prevent postoperative bleeding [29]. The most common local biosurgical hemostatic agents used in dentistry and approved by the Food and Drug Administration (FDA) are listed in Table 2.
\nTypes and trade name of some biosurgical agents–adapted from Pereira et al. [28].
Local biosurgical hemostatic agents can be classified into (A) passive or mechanical, (B) active, and (C) flowables [30].
\nConsidered as the most effective agents for small amounts of bleeding, passive or mechanical agents provide platelet activation and aggregation. This results in a matrix formation in the bleeding area that works as a barrier to stop bleeding, by activating the extrinsic clotting pathway and providing a surface that will allow coagulation to occur faster [30]. As these agents are biologically inactive, they rely on the individual’s own fibrin production to attain hemostasis. Passive hemostats are only indicated for individuals with an unscathed coagulation cascade [27]. They are generally applied as frontline agents, since they are readily available, do not require special storage or handling, and are relatively affordable [14, 27, 31].
\nGelatin is a hydrocolloid derived from acid partial hydrolysis of purified animal collagen. It is presented as a gelatin sponge, powder (mixed to form a paste), or film. Gelatin can be placed dry or after moistening it with saline [14, 28, 32, 33]. Gelatin-based products adapt effortlessly to wounds making it appropriate for application into irregular surfaces [27]. Although their mode of action is not completely understood, gelatin-based products likely act more physically than chemically in the coagulation cascade [28, 34]. Affordability, ease of use and good hemostatic activity make topical hemostats with gelatin matrix a popular tool for reducing the morbidity caused by hemorrhage [27, 28] after dental extractions and periodontal surgeries.
\nThe most popular absorbable gelatin sponge in dentistry is Gelfoam®. It is a hemostatic compressed sponge obtained from purified porcine skin gelatin. Gelfoam® is capable of absorbing many times its weight of whole blood [35]. Generally, when applied in soft tissues, its complete absorption occurs within 4–6 weeks.
\nCollagen absorbable products are nontoxic and non-pyrogenic. They are sourced from either bovine dermal collagen or bovine tendon. Collagen hemostats provide a matrix for clot formation and consolidation. These products also improve clotting factor release and platelet aggregation and degranulation, thereby breaking up clot formation. Their presentation in sheets and flours allows for easy adaptation and adhesion to irregular surfaces. Although they are commercialized at a higher price than gelatin-based hemostats, hemostasis can usually be accomplished relatively quicker (1–5 min). Collagen absorbable products are easily removed, reducing the risks of rebleeding and the need for various applications. They are absorbed in 8–10 weeks if remained in place. Adverse effects linked to bovine collagen products might include swelling and allergic reaction [30].
\nHelistat® is a collagen-based product originated from purified and freeze-dried bovine flexor tendon and is available as a spongelike structure [14, 27]. Helistat® can hold many times its own weight of fluid, as it is highly absorbent. Collagen induces platelet agglomeration when in contact with blood. In order to achieve hemostasis, Helistat® must be kept at the site (approximately 2–5 minutes). Subsequently, it can be removed, replaced, or left in place. It is easily manipulated, and it must be handled dry, and any excess must be removed. Complete reabsorption occurs within 14–56 days [14, 27, 36]. Helistat® may foster bacterial growth, acting as a nidus for abscess formation [14, 27, 37]; therefore, it should not be placed in wounds with any kind of contamination or infection. Possible adverse reactions of Helistat® or similar products are allergic reaction, foreign body reaction, and adhesion formation [27, 38].
\nSimple oxidized cellulose was first introduced in the early 1940s in the USA. In the 1960s, a new topical hemostatic-oxidized regenerated cellulose (ORC) was launched as a meshwork made from treated and sterilized cellulose—Surgicel®. ORC products are originated from vegetal-based alpha cellulose, available in absorbable knitted fabrics (low or high density), and prepared as sterile fabric meshworks. They are ready-to-use products that may be kept at room temperature and absorb 7–10 times its own weight [27, 30]. ORC cause contact activation and platelet activation, and, when absorbed, a gelatinous mass is created, assisting in the establishment of the clot formation [30]. Thrombin is ineffective with these agents due to low-pH factors. ORC are utilized in the management of capillary, venous, and small arterial bleeding, and they require dry application, without addition of saline or thrombin [27, 39] and are absorbed within 4–8 weeks, depending on the volume applied, the tissue bed, and the magnitude of blood saturation [27, 40, 41, 42]. To prevent delayed healing, excessive volumes should be removed [27]. ORC should not be used in osseous defects as it may intervene with bone regeneration [14, 27, 31]. Adverse effects also include reactions related to the acidic nature of ORC. This characteristic may induce necrosis and inflammation of the surrounding tissue and makes thrombin inefficient with these agents. When left in the wound, they may lead to fluid encapsulation and foreign body reaction [14, 27].
\nThe most common commercial products in this category are Surgicel®, Oxycel®, and Surgicel Nu-Knit®. Surgicel® and Surgicel Nu-Knit® come in knit, solid fiber form, whereas Oxycel® comes in knit, hollow fiber form; however, they function basically in a similar manner [30].
\nOxidized cellulose (OC) agents are produced from sterilized and treated cellulose, presented as a meshwork. In the presence of blood, they present a three- to fourfold increase in volume and are converted into gel. OC dissolve completely in 1–2 weeks into biodegradable end products glucose and water, and they do not interfere with wound healing [14, 27].
\nActCel® binds to calcium ions, resulting in more calcium available for the coagulation cascade [14, 27, 37]. Biochemically, it intensifies the coagulation process by increasing platelet aggregation and physically by 3D clot stabilization. ActCel® is especially indicated in third molar extractions, to avoid the occurrence of dry sockets, and in orthognathic and periodontal surgeries [27]. ActCel® is hypoallergenic, as it does not contain collagen, thrombin, or chemical additives. It also has important bacteriostatic properties [27, 43], which are particularity relevant in infected wounds [27].
\nGelita-Cel® is a relatively quick acting, oxidized resorbable cellulose hemostatic gauze of natural origin. It presents a decreased risk for encapsulation, as it resorbs as fast as 96 hours [14, 27, 37].
\nPolysaccharide hemospheres are a fairly new class of topical biosurgical hemostatic agents, produced from vegetable starch, and they contain no animal or human elements. They are commercially presented in powder form. Polysaccharide hemospheres increase barrier formation by creating a hydrophilic effect, dehydrating the blood, and concentrating its solid components [14, 27]. Due to their 3D scaffold, they are devised to enhance clot formation and organization, even in the absence of intrinsic coagulation activity [14, 44, 45]. Polysaccharide hemospheres should be used with caution in diabetic patients, as they consist of sugars [27].
\nArista™AH is the only FDA-approved product in the polysaccharide hemosphere category. It is used in dental surgery as an adjunctive hemostatic agent, when conventional mechanical procedures, such as pressure and ligature, are not effective or practical.
\nHemostatic adhesives are often used as adjuncts to standard hemostatic procedures to control bleeding from surgical areas [30]. One of the most well-known products in this category is BioGlue®. It consists of a solution of 10% glutaraldehyde and 45% bovine albumin solution purified by precipitation, heat, and chromatography radiation [28, 46]. BioGlue® has been extensively used for its sealants and hemostatic characteristics. The risk of leaking through the suture tracks is the main disadvantage of BiolGue® [27]. In the search for newly created adhesives with the chemical features and the safe reabsorptive profile required to benefit dental surgery patients, several clinical trials are currently in process.
\nActive hemostatic agents are biologically active, as they play a direct role in the coagulation cascade, inducing the formation of a fibrin clot [26, 27].
\nThrombin is key to hemostasis, as well as to the inflammatory and cell signaling processes. It is the base of the fibrin clot, fostering the transformation of fibrinogen to fibrin [28]. Topical thrombin hemostats are originated from either bovine or human plasma, and they can also be produced through recombinant DNA techniques [14, 27]. In the past, the only thrombin hemostat available was composed of bovine plasma (Thrombin-JMI). Although it has proven to be efficient in terminating bleeding, bovine thrombin induces an important immune response [28, 47]. Individuals on hemodialysis, with increased levels of antibodies against topical bovine thrombin, had higher incidence of vascular access thrombosis, severe coagulopathy, and bleeding after exposure to bovine thrombin [28, 48]. As an attempt to avoid these hazardous effects, thrombin derived from human plasma (Evithrom®) and recombinant human thrombin (Recothrom®) were developed. In 2010, Browman et al. [49] demonstrated, in a comparative study between recombinant human thrombin and bovine thrombin, that human recombinant thrombin showed the same efficacy in surgical hemostasis, a comparable safety profile, and a remarkably lower immune response than bovine thrombin. Thrombin may be applied topically, as a solution combined with gelatin sponges mixed with a gelatin matrix, as a dry powder, or as a spray [14, 27]. It is commonly used in conjunction with Gelfoam® to stop moderate to severe bleeding.
\nFibrin sealant or fibrin glue originates from bovine and/or human blood components and simulates the last phases of the coagulation cascade, generating a fibrin clot [30]. These agents control local, as well as diffuse, bleeding from the surgical area. Nevertheless, they are ineffective in controlling intense bleeding. Its use in dentistry includes tooth extraction sites, bone grafting, and periodontal surgery [14].
\nTisseel® was the first fibrin sealant approved by the FDA. It has in its composition human thrombin and fibrinogen, intermixed with aprotinin and CaCl2. Because aprotinin is a bovine protein, it is a potential allergen. Multiple exposures may cause allergic reactions, as well as anaphylactic reaction approaching lethality [30, 50]. As for its ideal application, a dry operating field is required; Tisseel® is particularly effective when applied prior to bleeding. In this situation, fibrinogen may polymerize before blood pressure increases local microcirculation flow. When used after the onset of bleeding, one should apply local pressure over the wound to allow polymerization [28, 51]. Tisseel® is available in a pre-filled syringe, allowing for effective application using the EasySpray and DuploSpray MIS systems.
\nAnother option for fibrin sealants, Evicel®, originates from pooled human plasma. It is available as two separate vials of fibrinogen and human thrombin. Prior to use, the two deep frozen solutions must be thawed and mixed after defrosting and heating up (20–30°C) [30].
\nCrosseal™ is a virally inactivated, second-generation surgical sealant. It is produced from concentrated human clottable proteins, namely, biological active component (BAC), which contains the active component fibrinogen, and human α-thrombin (1000 IU/ml) [52]. This fibrin sealant is applied using an application device which drips/sprays Crosseal™ onto the bleeding site.
\nThere are two main categories of flowable biosurgicals: products containing porcine gelatin, which can be combined with thrombins (bovine, human-pooled plasma thrombin, or rhThrombin), and bovine collagen-based agents, packed with human-pooled plasma thrombin. The flowable agents are deemed the most effective of all the local hemostatic agents [30, 53].
\nSurgiflo® is an absorbable, sterile, hemostatic porcine gelatin matrix, combined with Thrombin-JMI, a topical bovine-derived thrombin. It should be placed directly to the bleeding areas to activate the hemostatic process [30]. A compression period is required for polymerization of the sealant components [28].
\nFloseal® consists of a bovine gelatin matrix, plasma-extracted human thrombin, and CaCl2. Its gelatin granules expand (10–20%), as it comes in contact with blood, producing a seal when the product is applied to a bleeding area [27, 30]. The thrombin fraction of the product triggers the regular pathway of the coagulation cascade, converting fibrinogen to a fibrin polymer and creating a clot around the firm matrix [27], which is reabsorbed within the expected period of standard wound healing (6–8 weeks) [14, 27, 33, 42, 54]. A distinctive feature of Floseal® is the need for the presence of blood for activation [30, 55]. Neither compression, nor a dry surgical field is required for its application [28].
\nBecause of this biosurgical flowability, they can easily adapt to irregular wounds. Flowables have been utilized as frontline topical hemostats in major dental surgeries, in patients where conventional procedures are ineffective. They can be utilized as an adjunct to hemostasis in practically all dental surgical interventions. Flowables are effective on both hard and soft tissues [27, 30]. They have a risk of transmitting infectious agents and are contraindicated in patients who are allergic to materials of bovine origin [27].
\nAlthough traditional methods, such as ligature and manual pressure, can promote hemostasis, they are not an effective approach of bleeding control in less accessible sites and complex injuries. Furthermore, bleeding control is especially challenging in patients presenting acquired or congenital coagulation disorders.
\nTopical biosurgical hemostatic agents comprise a wide range of products aiming at minimizing the risk of bleeding. In recent years, several clinical trials have analyzed the effectiveness, advantages, and limitations of biosurgicals, as well as performed comparisons among the different types of biosurgicals and other non-biologic agents. Despite the beneficial effect of these local hemostatic agents in preventing bleeding in dental surgery, available data comparing their effectiveness and efficiency is still scarce and inconclusive. Methodological heterogeneities, such as the lack of a standard therapy and comparable treatment regimens, are noticeable among studies, as well as the reduced number of randomized controlled trials [2, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70].
\nIn summary, local hemostatic agents are very distinct products with diverse indications. Presently, there is no definite evidence-based approach to guide the dental practitioner when selecting a local hemostatic agent. They must be aware of the characteristics of each single hemostatic agent, to elect the most suitable product for every particular clinical situation. In addition, current available data shows that no topical agent can be regarded as superior or more effective than the others [2]. Further experimental research and controlled clinical trials are warranted to define the most cost-effective biosurgical hemostatic agents in dentistry.
\nThe dental practitioner should assess the bleeding risk of the patient, as well as the bleeding risk of the surgical intervention, preoperatively. After assessing both bleeding risks, the professional can then conceive an intraoperative and postoperative plan. The international normalized ratio (INR) must be evaluated in patients reporting an elevated risk of bleeding. While a standard parameter of coagulation has an INR of 1 [71], the therapeutic range runs from 2.0 to 3.5. In this case, it is recommended to use local hemostatic measures independently or in combination with conventional methods. These agents can be used before, during, and after dental surgeries.
\n\n
Comprehensive medical history, including all medications in the patient’s regimen, to identify potential bleeding issues prior to the surgery [26].
In order to decrease surgical bleeding, patients receiving anticoagulant therapy may need to break up exodontia into multiple appointments [26, 72].
Laboratory values such as platelet count, INR, and prothrombin time are of critical value in medically compromised patients [26].
Demographic risk factors (female sex and older age) [73].
Supplemental patient-related risk determinants: diabetes mellitus, hypertension, obesity, hemostatic disorders, renal impairment, and other major organ system failures [73, 74, 75].
Timing of the appointment: early morning visits allowing patients to return to the dental office in case of postsurgical hemorrhage [26].
Patients at a higher bleeding risk are those reporting family history of bleeding and previous bleeding problems after dental surgery or trauma and individuals using medications, such as aspirin, anticoagulants, and/or long-term antibiotics. Any illnesses associated with bleeding problems, such as leukemia, congenital heart disease, liver disease, or hemophilia, present a higher risk of bleeding. The dental professional needs to be aware and prepared for any intercurrence, during or after a surgical procedure. Individuals presenting advanced periodontal disease are also considered as having a higher risk of perioperative bleeding. In such cases, the surgical plan should include a preoperative phase, consisting of scaling and root planning and a proper chlorhexidine gluconate mouth rinse regimen, 2 weeks before an elective procedure [26].
\nThe risk of bleeding of a dental intervention may be ranked as high, moderate, and low [25, 76, 77, 78]. In most patients, antithrombotic therapy is not interrupted before dental interventions with low bleeding risk, due to the disastrous complications of thrombosis (Table 3) [25, 76, 77, 78]. Moderate and high bleeding potential interventions might need the temporary discontinuation of the antithrombotic therapy [25, 76, 77, 78].
\nDental interventions that do not require anticoagulation therapy interruption*–adapted from Kaplovitch and Dounaevskaia [25].
Dental surgical interventions are considered by most recommendations, as minor procedures presenting self-limited blood loss and low bleeding risk. Bleeding, in most cases, can be managed with local hemostatic agents [79, 80].
\nThe dental care of individuals receiving therapeutic anticoagulation becomes critical when invasive procedures are needed. At this time, the clinician must decide either to maintain the anticoagulation therapy and risk bleeding complications or withdraw the anticoagulation medication and risk developing systemic thrombosis [1]. After decades of controversial data, there is currently a nearly unanimous consensus that anticoagulation therapy, for most dental surgeries, should not be discontinued. The higher risk of bleeding complications is compensated by the elevated risk of developing thromboembolic complications [1, 81, 82, 83, 84].
\nNational dental and medical group statements and multiple evidence-based clinical guidelines have considered the issue independently and support the maintenance, for most dental patients, of anticoagulation therapy (American Dental Association; American Academy of Dental Sleep Medicine; American Heart Association; American College of Cardiology; American Academy of Neurology; American Society of Anesthesiologists; Society for Neuroscience in Anesthesiology and Critical Care; American College of Chest Physicians (ACCP)) [1]. In a 2012 statement [76], the ACCP recommended continuing anticoagulation therapy with warfarin, with the additional utilization of a local hemostatic. The ACCP advised a 2–3-day anticoagulation therapy suspension, in order to lower the INR levels to a range of 1.6 and 1.9 [76, 85].
\nLately, the dental care of patients receiving anticoagulant treatment has been the focus of expressive scientific interest, in both dental and medical fields. A recent literature review showed that only 31 (0.6%) of more than 5400 patients receiving over 11,300 dental surgical interventions while continuing to take vitamin K antagonist anticoagulants (warfarin in most cases) demanded more than local maneuvers for hemostasis. No cases of fatal hemorrhage were reported. In over 2600 individuals whose anticoagulation was discontinued for dental interventions, 22 thromboembolic complications (0.8% of medication withheld), including 6 fatal events (0.2% of medication withheld), were observed [83]. Similar results have been shown in a literature review of dental surgery and antiplatelet medications. Of more than 1200 patients receiving over 2300 dental surgical procedures while continuing their antiplatelet medications (aspirin in most cases), only 2 (0.2%) needed more than local measures for hemostasis. Conversely, in over 320 individuals undergoing 370 antiplatelet interruptions for dental procedures, 17 (5.3%) suffered thromboembolic complications [86].
\nAvailable data shows that the majority of dental interventions can be safely conducted in patients receiving anticoagulation treatment, when considering older medications [4]. However, there are fewer studies reporting the provision of dental care in individuals using newer direct oral anticoagulants. The clinical implications of these newer anticoagulant and antiplatelet therapies have only been recently investigated [80, 87]. The protocol followed by the dental practitioner when managing these patients varies significantly and shows inconsistencies reflecting the lack of large-scale studies and evidence-based clinical guidelines [80, 88, 89]. The risk of postoperative bleeding after invasive periodontal treatment in individuals using different anticoagulation therapies was assessed, retrospectively, in 456 individuals receiving an antiplatelet and/or anticoagulant therapy [90]. Data was collected after 484 invasive periodontal interventions, with 99.6% of patients continuing their medications during the procedures. Postoperative bleeding was reported only following three interventions (0.35%), and it was controlled with local hemostatic maneuvers. Although the authors did not specify which type of local hemostatic procedure was used, this retrospective study showed a very low risk of bleeding in patients receiving an invasive periodontal intervention while using an anticoagulant or antiplatelet medication [90]. These results support the recommendation that such medications do not need to be discontinued in anticipation to invasive periodontal interventions.
\nExtended inter- or postoperative bleeding following dental surgery is infrequent, seldom demanding anything more than the use of local hemostatic biosurgicals. The judgment of whether or not to interrupt anticoagulation treatment can be both intricate and dynamic, and it should be based on the indication for pharmacological therapy, as well as previous thromboembolic history. The discontinuation of anticoagulant therapy may be required in dental interventions with moderate and high bleeding risk [25, 76, 77, 78]. Currently, most clinicians dealing with anticoagulant management tend to personalize the periprocedural management of the bleeding potential, according to the individual risk of each procedure—low, moderate, or high—following the current clinical practice recommendations based on best evidence and maintaining the anticoagulant therapy. Thereby, the patient anticoagulant regimen should be continued in specific low-risk dental procedures, without consultation or fear of disproportionate bleeding demanding additional intervention (Table 3) [25].
\nUndoubtedly, anticoagulant agents are effective in preventing thromboembolism. Nevertheless, their potential for critical adverse effects cannot be ignored. The use of antithrombotic medications is the most frequent cause of an adverse drug event requiring individuals to seek out emergency care [25, 91]. The majority of drug interactions with anticoagulants lead to elevated risk of bleeding. The nature of the interactions cannot be predicted, as they are expressed through both pharmacodynamic mechanisms and pharmacokinetic properties [25].
\nRegarding patient safety, potential risk for interaction, as well as knowledge of appropriate prescribing and monitoring, is crucial. Equally decisive is selecting the appropriate anticoagulant agent and monitoring the potential for drug–drug interaction [10, 11, 12, 13, 14, 15, 17, 25]. Common anticoagulants and their interaction with the most common medications prescribed for dental patients are described in Table 4 [25, 92, 93, 94, 95, 96, 97, 98].
\nCommon anticoagulants and potential interactions with dental medications–adapted from Kaplovitch and Dounaevskaia [25].
Most studies evaluating the occurrence of peri- and postoperative bleeding show anticoagulation therapy can be maintained when adequate local hemostatic maneuvers are used.
\nAs an example, a controlled clinical trial compared the occurrence of bleeding following dental extractions in individuals receiving oral anticoagulants (experimental group) versus patients that had never received oral anticoagulant therapy (control group). Tooth extractions were performed, and a piece of oxidized cellulose was placed only into the sockets in the experimental group. The wound borders were sutured, and a gauze saturated with tranexamic for 30–60 minutes was applied with pressure in the wound. Both groups presented similar bleeding complications [99]. In a similar clinical trial [100], 161 tooth extractions were performed in patients undertaking warfarin. After tooth extraction, an oxidized cellulose gauze was placed in the socket, and the wound was sutured. Patients were assigned to four groups, according to their INR range (INR was 1.5–1.99 in group 1; 2.0–2.49 in group 2; 2.5–2.99 in group 3; and 3.0–3.7 in group 4). No significant differences were found in the postoperative bleeding among groups.
\nBased on the latest evidence and clinical practice recommendations on the perioperative management of dental patients receiving direct oral anticoagulants, on single or dual antiplatelet therapy or vitamin K antagonists, as well as on the current scientific knowledge on biosurgical hemostatic agents, the following conclusions can be made:
The majority of dental procedures can be securely executed without the withholding of anticoagulants, using only local hemostatic therapy. In fact, current recommendations and consensus support the continuation of antiplatelet or anticoagulant therapy. Discontinuing these drugs can increase the risk of thromboembolism, at the cost of minor bleeding, which can be restrained without difficulty. The appropriate use of local hemostatic measures, such as topical biosurgical hemostatic agents, should always be considered whenever indicated.
In order to safely treat a patient receiving anticoagulant therapy, familiarity with anticoagulants and with the potential for drug–drug interactions is required, in addition to knowledge about the topical hemostatic options available.
Topical biosurgical hemostatic agents are diverse agents with distinct indications. The dental practitioner must be aware of the properties of each single agent, in order to properly select the product needed in each different clinical condition.
Based on current available data, no topical hemostatic agent can be regarded as superior or more effective than the others. Further experimental research and controlled clinical trials are warranted to define the most cost-effective biosurgical hemostatic agents in dentistry.
A definite protocol for excessive bleeding is still required for dental surgery in patients with hemorrhagic diathesis. The most effective local hemostatic agent with lesser complications should be determined in future research, considering their availability and cost-effectiveness.
The authors are grateful to Kisa Iqbal BSc Hons, DDS Candidate c/o 2020, New York University College of Dentistry, for editing this article.
\nThe authors declare no conflict of interest.
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Stauffer",coverURL:"https://cdn.intechopen.com/books/images_new/5838.jpg",editedByType:"Edited by",editors:[{id:"97565",title:"Dr.",name:"Mark",middleName:"Thomas",surname:"Stauffer",slug:"mark-stauffer",fullName:"Mark Stauffer"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5766",title:"Food Additives",subtitle:null,isOpenForSubmission:!1,hash:"db60517de698281a1de9b335dd171236",slug:"food-additives",bookSignature:"Desiree Nedra Karunaratne and Geethi Pamunuwa",coverURL:"https://cdn.intechopen.com/books/images_new/5766.jpg",editedByType:"Edited by",editors:[{id:"130501",title:"Prof.",name:"Desiree Nedra",middleName:null,surname:"Karunaratne",slug:"desiree-nedra-karunaratne",fullName:"Desiree Nedra Karunaratne"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1484",title:"Soybean",subtitle:"Molecular Aspects of Breeding",isOpenForSubmission:!1,hash:"3bd8fd078e7df24f2eed6dc7bc226475",slug:"soybean-molecular-aspects-of-breeding",bookSignature:"Aleksandra Sudaric",coverURL:"https://cdn.intechopen.com/books/images_new/1484.jpg",editedByType:"Edited by",editors:[{id:"21485",title:"Dr.",name:"Aleksandra",middleName:null,surname:"Sudarić",slug:"aleksandra-sudaric",fullName:"Aleksandra Sudarić"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:7,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"14941",doi:"10.5772/14407",title:"Evolution of Soybean Aphid Biotypes: Understanding and Managing Virulence to Host-Plant Resistance",slug:"evolution-of-soybean-aphid-biotypes-understanding-and-managing-virulence-to-host-plant-resistance",totalDownloads:3437,totalCrossrefCites:2,totalDimensionsCites:34,abstract:null,book:{id:"1484",slug:"soybean-molecular-aspects-of-breeding",title:"Soybean",fullTitle:"Soybean - Molecular Aspects of Breeding"},signatures:"Andrew P. Michel, Omprakash Mittapalli and M. A. Rouf Mian",authors:[{id:"17721",title:"Dr.",name:"Andrew P.",middleName:null,surname:"Michel",slug:"andrew-p.-michel",fullName:"Andrew P. Michel"},{id:"22017",title:"Dr.",name:"Omprakash",middleName:null,surname:"Mittapalli",slug:"omprakash-mittapalli",fullName:"Omprakash Mittapalli"},{id:"22018",title:"Dr.",name:"M. A. Rouf",middleName:null,surname:"Mian",slug:"m.-a.-rouf-mian",fullName:"M. A. Rouf Mian"}]},{id:"63469",doi:"10.5772/intechopen.80869",title:"Use of Natural Antimicrobial Agents: A Safe Preservation Approach",slug:"use-of-natural-antimicrobial-agents-a-safe-preservation-approach",totalDownloads:2881,totalCrossrefCites:15,totalDimensionsCites:31,abstract:"Microorganism contamination at various stages of food chain is one of the major causes for food spoilage that ultimately leads to food waste, increasing food insecurity issues and substantial economic losses. Various synthetic chemical preservatives are being used to control microbial food spoilage and to extend product shelf life. Researchers and consumers are discouraging the use of synthetic preservatives due to their negative health impacts. Naturally occurring antimicrobials have gained attention among researchers and food manufacturer due to their safety and nontoxic status. Natural preservatives are easy to obtain from plants, animals and microbes. These naturally occurring antimicrobial agents can be isolated from indigenous sources using various advanced techniques. Natural preservatives such as nisin, essential oils, and natamycin have effective potential against spoilage and pathogenic microorganisms. The regulations regarding the use of these naturally occurring preservatives are not well defined in some developing countries. This chapter focuses on source and their potential role, antimicrobial mechanism in food preservation, and current knowledge on the subject.",book:{id:"7261",slug:"active-antimicrobial-food-packaging",title:"Active Antimicrobial Food Packaging",fullTitle:"Active Antimicrobial Food Packaging"},signatures:"Farhan Saeed, Muhammad Afzaal, Tabussam Tufail and Aftab Ahmad",authors:[{id:"192244",title:"Dr.",name:"Farhan",middleName:null,surname:"Saeed",slug:"farhan-saeed",fullName:"Farhan Saeed"},{id:"232885",title:"Dr.",name:"Aftab",middleName:null,surname:"Ahmed",slug:"aftab-ahmed",fullName:"Aftab Ahmed"},{id:"245894",title:"Dr.",name:"Muhammad",middleName:null,surname:"Afzaal",slug:"muhammad-afzaal",fullName:"Muhammad Afzaal"},{id:"255994",title:"Mr.",name:"Tabussam",middleName:null,surname:"Tufail",slug:"tabussam-tufail",fullName:"Tabussam Tufail"}]},{id:"55599",doi:"10.5772/intechopen.69301",title:"Nutritional, Bioactive and Physicochemical Characteristics of Different Beetroot Formulations",slug:"nutritional-bioactive-and-physicochemical-characteristics-of-different-beetroot-formulations",totalDownloads:3880,totalCrossrefCites:12,totalDimensionsCites:24,abstract:"Beetroot possesses high nutritional value and is considered one of the main dietary sources of nitrate. Nitrate has increasingly attracted the interest of the scientific community regarding new physiological, nutritional and therapeutic approaches with beneficial effects on the cardiovascular system. These effects can be explained by the possible effect of dietary nitrate in stimulating nitric oxide synthesis. Dietary nitrate can be reduced to nitrite in the oral cavity, which is then decomposed to nitric oxide and other bioactive nitrogen oxides in the stomach. Beetroot administration can be conducted by several types of formulations, in order to provide a convenient and alternative source of dietary beetroot, such as beetroot juice or beetroot chips and powder. The challenge in providing a product which, in addition to being rich in nitrate, is attractive and easy to administer, while also being microbiologically safe, is increased by the limited scientific information available concerning the nutritional aspects of beetroot formulations. In this chapter, a brief review on the efficiency of different beetroot formulations on health indicators is conducted, emphasizing the effects following the intake of nitrate-enriched beetroot gel. The metabolic and hemodynamic effects of beetroot formulations in healthy and non-healthy volunteers are also discussed.",book:{id:"5766",slug:"food-additives",title:"Food Additives",fullTitle:"Food Additives"},signatures:"Diego dos S. Baião, Davi V.T. da Silva, Eduardo M. Del Aguila and\nVânia M. Flosi Paschoalin",authors:[{id:"97533",title:"Dr.",name:"Vania",middleName:null,surname:"Paschoalin",slug:"vania-paschoalin",fullName:"Vania Paschoalin"}]},{id:"56718",doi:"10.5772/intechopen.70197",title:"Natural Antimicrobials, their Sources and Food Safety",slug:"natural-antimicrobials-their-sources-and-food-safety",totalDownloads:3981,totalCrossrefCites:9,totalDimensionsCites:23,abstract:"With consumer awareness about food safety and quality, there is a high demand for the preservative (synthetic)-free foods and use of natural products as preservatives. Natural antimicrobials from different sources are used to preserve food from spoilage and pathogenic microorganisms. Plants (herbs and spices, fruits and vegetables, seeds and leaves) are the main source of antimicrobials and contain many essential oils that have preservation effect against different microorganisms. Mainly, herb and spices contain many essential oils and the examples include rosemary, sage, basil, oregano, thyme, cardamom, and clove. These essential oils are very effective against many pathogenic and spoilage microorganisms like Salmonella, Escherichia coli, Listeria monocytogenes, Campylobacter spp., and Staphylococcus aureus and help to increase their quality and shelf stability. These antimicrobial compounds are also used in combination with edible food coatings and inhibit the ability of microorganisms to grow on the surface of food and food products.",book:{id:"5766",slug:"food-additives",title:"Food Additives",fullTitle:"Food Additives"},signatures:"Muhammad Sajid Arshad and Syeda Ayesha Batool",authors:[{id:"192998",title:"Dr.",name:"Muhammad Sajid",middleName:null,surname:"Arshad",slug:"muhammad-sajid-arshad",fullName:"Muhammad Sajid Arshad"},{id:"209272",title:"Ms.",name:"Syeda Ayesha",middleName:null,surname:"Batool",slug:"syeda-ayesha-batool",fullName:"Syeda Ayesha Batool"}]},{id:"14938",doi:"10.5772/15688",title:"Phomopsis Seed Decay of Soybean",slug:"phomopsis-seed-decay-of-soybean",totalDownloads:4488,totalCrossrefCites:10,totalDimensionsCites:22,abstract:null,book:{id:"1484",slug:"soybean-molecular-aspects-of-breeding",title:"Soybean",fullTitle:"Soybean - Molecular Aspects of Breeding"},signatures:"Shuxian Li",authors:[{id:"21619",title:"Dr.",name:"Shuxian",middleName:null,surname:"Li",slug:"shuxian-li",fullName:"Shuxian Li"}]}],mostDownloadedChaptersLast30Days:[{id:"57363",title:"Some Aspects of Animal Feed Sampling and Analysis",slug:"some-aspects-of-animal-feed-sampling-and-analysis",totalDownloads:2875,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Animal feed plays an important part in the food chain and the composition and quality of the livestock products (milk, meat and eggs) that people consume. Animal feeds are either classified as fodder, forage, or mixed feeds. Fodders could be classified as roughages (fresh cut forage, hay or dry forage, straw, root crops, stover and silage) and concentrates such as grains, legumes and by-products of processing. Safety is perhaps one of the most important reasons for feed analysis by the manufacturers and consumers. Storage duration and conditions for feed samples, as well as of stable and unstable parameters are important in sample preparation. A number of sub-samples for preparing final sample for various categories of feed products are recommended. Some analysis conducted on feed include; dry matter, crude ash, ash insoluble in acid (sand), crude protein, crude fat, fibre analysis, starch, gross energy, minerals. More are amino acids (excluding tryptophan), amino acids (tryptophan), fatty acids, vitamins, reducing sugar, mycotoxins, and pesticides. Various types of samples depending on their purposes and uses are available from check, standard, working and referee samples to composite types. Sampling errors in procedures exists and can be minimized by standards or purposes of the analysis, appropriate sampling equipment and using the right quantity of materials.",book:{id:"5838",slug:"ideas-and-applications-toward-sample-preparation-for-food-and-beverage-analysis",title:"Ideas and Applications Toward Sample Preparation for Food and Beverage Analysis",fullTitle:"Ideas and Applications Toward Sample Preparation for Food and Beverage Analysis"},signatures:"Gabriel Adebayo Malomo and Nnemeka Edith Ihegwuagu",authors:[{id:"94246",title:"Dr.",name:"Nnemeka",middleName:"Edith",surname:"Ihegwuagu",slug:"nnemeka-ihegwuagu",fullName:"Nnemeka Ihegwuagu"},{id:"217809",title:"Dr.",name:"Gabriel",middleName:null,surname:"Malomo",slug:"gabriel-malomo",fullName:"Gabriel Malomo"}]},{id:"56317",title:"Food Additives and Processing Aids used in Breadmaking",slug:"food-additives-and-processing-aids-used-in-breadmaking",totalDownloads:3777,totalCrossrefCites:8,totalDimensionsCites:9,abstract:"The main classes of additives used in breadmaking are: (i) oxidants/reductants; (ii) emulsifiers; (iii) hydrocolloids; and (iv) preservatives. The main processing aids used are enzymes. Historically, market trends have developed from the use of ingredients in greater quantities - to obtain specific effects in bread (such as fat for crumb softness) - to the use of additives at much lower levels (max. 1%) and, more recently, to enzymes which are used in parts per million (ppm). According to many regulations, enzymes do not need to be declared on the label of the final product, attending the “clean label” trend. We will describe the food additives used under each class, individually describing their mode of action and effects on dough rheology, during the breadmaking process, and on product quality. We will also describe the main enzymes currently used, dividing them according to the substrate they act on (gluten, starch, lipids, non-starch polysaccharides or NSPS), individually describing their mode of action and effects on dough rheology, during the breadmaking process, and on product quality. Legal aspects will also be addressed. We will conclude with future trends in the use of additives and processing aids in breadmaking.",book:{id:"5766",slug:"food-additives",title:"Food Additives",fullTitle:"Food Additives"},signatures:"Luis Carlos Gioia, José Ricardo Ganancio and Caroline Joy Steel",authors:[{id:"196530",title:"Prof.",name:"Caroline",middleName:"Joy",surname:"Steel",slug:"caroline-steel",fullName:"Caroline Steel"},{id:"197499",title:"BSc.",name:"Luis Carlos",middleName:null,surname:"Gioia Jr.",slug:"luis-carlos-gioia-jr.",fullName:"Luis Carlos Gioia Jr."},{id:"197500",title:"BSc.",name:"José Ricardo",middleName:null,surname:"Crepaldi Ganancio",slug:"jose-ricardo-crepaldi-ganancio",fullName:"José Ricardo Crepaldi Ganancio"}]},{id:"60470",title:"Contamination, Prevention and Control of Listeria monocytogenes in Food Processing and Food Service Environments",slug:"contamination-prevention-and-control-of-listeria-monocytogenes-in-food-processing-and-food-service-e",totalDownloads:2090,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"This chapter reviews issues related to the occurrence and growth of Listeria monocytogenes in food processing and food service environments. L. monocytogenes is a food-borne pathogen with the capacity to contaminate raw or minimally processed foods such as chilled ready-to-eat (RTE) foods. The consumption of food contaminated with L. monocytogenes can result in a disease known as listeriosis among vulnerable groups of people such as pregnant women and fetuses, newborns, adults between the ages of 65 and 75, and people with weakened immune systems. L. monocytogenes is ubiquitous and has been isolated from soil, vegetation, sewage, water, animal feed, fresh and frozen meat including poultry, slaughterhouse wastes and the feces of healthy animals and humans. The bacterium is both acid tolerant and salt tolerant. It is able to grow at refrigerator temperature, and is therefore often associated with the consumption of raw or minimally processed and often chilled RTE foods. L. monocytogenes is able to form biofilms on food processing and preparation surfaces, which protects it from antimicrobial action. Continuous education of vulnerable groups regarding food safety will increase their awareness of the importance of practicing safer food handling practices such as hand washing and safe storage of RTE foods as a means to prevent listeriosis.",book:{id:"6648",slug:"listeria-monocytogenes",title:"Listeria Monocytogenes",fullTitle:"Listeria Monocytogenes"},signatures:"Frederick Tawi Tabit",authors:[{id:"229896",title:"Dr.",name:"Frederick Tawi",middleName:null,surname:"Tabit",slug:"frederick-tawi-tabit",fullName:"Frederick Tawi Tabit"}]},{id:"56718",title:"Natural Antimicrobials, their Sources and Food Safety",slug:"natural-antimicrobials-their-sources-and-food-safety",totalDownloads:3982,totalCrossrefCites:9,totalDimensionsCites:23,abstract:"With consumer awareness about food safety and quality, there is a high demand for the preservative (synthetic)-free foods and use of natural products as preservatives. Natural antimicrobials from different sources are used to preserve food from spoilage and pathogenic microorganisms. Plants (herbs and spices, fruits and vegetables, seeds and leaves) are the main source of antimicrobials and contain many essential oils that have preservation effect against different microorganisms. Mainly, herb and spices contain many essential oils and the examples include rosemary, sage, basil, oregano, thyme, cardamom, and clove. These essential oils are very effective against many pathogenic and spoilage microorganisms like Salmonella, Escherichia coli, Listeria monocytogenes, Campylobacter spp., and Staphylococcus aureus and help to increase their quality and shelf stability. These antimicrobial compounds are also used in combination with edible food coatings and inhibit the ability of microorganisms to grow on the surface of food and food products.",book:{id:"5766",slug:"food-additives",title:"Food Additives",fullTitle:"Food Additives"},signatures:"Muhammad Sajid Arshad and Syeda Ayesha Batool",authors:[{id:"192998",title:"Dr.",name:"Muhammad Sajid",middleName:null,surname:"Arshad",slug:"muhammad-sajid-arshad",fullName:"Muhammad Sajid Arshad"},{id:"209272",title:"Ms.",name:"Syeda Ayesha",middleName:null,surname:"Batool",slug:"syeda-ayesha-batool",fullName:"Syeda Ayesha Batool"}]},{id:"77442",title:"Fermentation of Cocoa Beans",slug:"fermentation-of-cocoa-beans",totalDownloads:414,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Cocoa bean fermentation is a spontaneous process driven by an ordered microbial succession of a wide range of yeasts, lactic acid and acetic acid bacteria, some aerobic sporeforming bacteria and various species of filamentous fungi. The process of cocoa fermentation is a very important step for developing chocolate flavor precursors which are attributable to the metabolism of succession microbial. The microbial ecology of cocoa has been studied in much of the world. In Venezuela, studies have been carried out with Criollo, Forastero, and Trinitario cocoa, fermented under various conditions, the results obtained coinciding with the reported scientific information. Fermentation must be associated with the type of cocoa available, carried out knowing the final processing and derivative (paste, butter, powder). The results shown in this chapter correspond to investigations carried out with cocoa from three locations in Venezuela. The quantification, identification, isolation, functionality of the most representative microbiota involved in the fermentation of these grains was sought. This to give possible answers to the fermentation times and improvement of the commercial quality. Likewise, generate greater interest on the part of the producers in carrying out the fermentation.",book:{id:"9709",slug:"fermentation-processes-benefits-and-risks",title:"Fermentation",fullTitle:"Fermentation - Processes, Benefits and Risks"},signatures:"Romel E. Guzmán-Alvarez and José G. Márquez-Ramos",authors:[{id:"238233",title:"Dr.",name:"Romel",middleName:null,surname:"E. Guzmán-Alvarez",slug:"romel-e.-guzman-alvarez",fullName:"Romel E. Guzmán-Alvarez"},{id:"269154",title:"Dr.",name:"José",middleName:null,surname:"G. Márquez-Ramos",slug:"jose-g.-marquez-ramos",fullName:"José G. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. 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He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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