Incident likelihood and risk scoring (risk scoring = consequence x likelihood).
\r\n\t
",isbn:"978-1-80355-403-7",printIsbn:"978-1-80355-402-0",pdfIsbn:"978-1-80355-404-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"360fe5dabd12a1f91a5658a5fe3eff66",bookSignature:"Associate Prof. Murat Eyvaz and Dr. Ahmed Albahnasawi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11934.jpg",keywords:"Hydrogen Sources, Hydrogen Production, Hydrogen Safety, Hydrogen Storage Methods, Environmental Impacts of Hydrogen, Synthetic Fertilizer Production, Aromatization, Hydrocracking, Hydrodesulfurization, Fuel Cells, Gas Turbines, Hydrogen Driven Vehicles",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 18th 2022",dateEndSecondStepPublish:"March 18th 2022",dateEndThirdStepPublish:"May 17th 2022",dateEndFourthStepPublish:"August 5th 2022",dateEndFifthStepPublish:"October 4th 2022",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Eyvaz is a pioneering researcher in environmental sciences and engineering, who has co-authored numerous journal articles and conference papers and has four patents on wastewater treatment systems.",coeditorOneBiosketch:"Dr. Albahnasawi is a pioneering researcher in environmental sciences and engineering, who has co-authored numerous journal articles and conference papers on water and wastewater treatment and waste remediation.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"170083",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Eyvaz",slug:"murat-eyvaz",fullName:"Murat Eyvaz",profilePictureURL:"https://mts.intechopen.com/storage/users/170083/images/system/170083.png",biography:"Dr. Murat Eyvaz is an associate professor in the Environmental Engineering Department, Gebze Technical University, Turkey. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49195",title:"Current Trends in the Production of Cellulose Nanoparticles and Nanocomposites for Biomedical Applications",doi:"10.5772/61334",slug:"current-trends-in-the-production-of-cellulose-nanoparticles-and-nanocomposites-for-biomedical-applic",body:'Cellulose is the most abundant, renewable, and sustainable biopolymer on earth. It is present in plants, tunicates, and some bacteria. For instance, it is present in the cell wall of wood fibers along with hemicellulose and lignin. The cellulose fibers are composed of microfibrils that, in turn, are composed of elementary fibrils, which are the basic structural units. These elementary fibrils or nanofibers are about 2–20 nm in diameter and a few micrometers in length. About 30 to 100 cellulose chains aggregate into an elementary fibril. There are regions within each of these elementary fibrils, where the cellulose chains are arranged in highly ordered (crystalline) structures and regions that are disordered (amorphous) [1]. These elementary fibrils are formed during cellulose biosynthesis. Each microfibril is a flexible hair strand composed of cellulose nanocrystals (CNC) linked along with cellulose nanofibers (CNF) [2] (Fig. 1). The terms nanofibrils, nanofibers, and elementary fibrils are usually employed as synonyms. A CNF is a bulky, moderately degraded cellulose with a large surface area with diameter ranging from 20 to 60 nm and length of several micrometers. It presents a weblike structure, and the length/diameter ratio is very high. They are usually extracted by mechanical treatment without using acid hydrolysis. Conversely, when subjected to acid hydrolysis, cellulose microfibrils undergo transverse cleavage along the amorphous regions, and the use of sonication results in CNC also referred as cellulose nanowhiskers, or nanorods. Thus, CNCs are described as the crystalline region of cellulose and exhibits a rodlike shape having a low aspect ratio [2, 3]. Its elastic modulus can be compared to the modulus of crystalline cellulose (up to 140 GPa) due to its high hydrogen bonding capability. Further, cellulose nanoparticles degrade faster than other nanoparticles such as fullerenes and carbon nanotubes, which do not degrade at all [4].
Another type of nanocellulose is bacterial cellulose (BC), which is produced as an extracellular primary metabolite by bacteria belonging to the genera
Hierarchical structure of cellulose extracted from plants.
CNF is mainly extracted from wood. However, it can be extracted from natural resources such as such as sisal [15], flax, hemp, grass [16], sorghum, barley, sugar cane [17], pineapple leaf fibers [18], banana rachis [19], soy hulls [20], algae [21], bacterial cellulose, kenaf stem, swede root, wheat straw [22], carrots, empty fruit bunches, potato pulp, branch bark of mulberry [23], bagasse, rice straw, chardonnay grape skins [24], stems of cacti, coconut husk [25], bamboo, pea hull fiber, cotton and industrial bioresidues [26]. Pineapple leaf and jute fibers are the best sources for its extraction due to the low cost, abundance, and high cellulose content [60–70%) [27]. The size of CNF depends on the source and exhibits an entangled morphology with an aspect ratio over 250. For instance, CNF obtained from wheat straw, soy hull, and soybean stock have diameters ranging from 10 to 80 nm, from 20 to 120 nm, and from 50 to 100 nm, respectively [28, 29]. Nevertheless, other researchers have obtained CNF from sisal, carrots, beet pulp, and Luffa cylindrical with smaller diameters of 20–65 nm, 3–36 nm, 30–100 nm, and 55 nm, respectively. These nonwooden sources contain less lignin and require less processing steps and energy consumption due to the less tightly bound microfibril in the primary cell wall than wood. There are several extraction methods to obtain CNF [30–32] (Fig. 2). They can be performed by mechanical techniques such as grinding, cryocrushing with liquid nitrogen, high-pressure homogenization, etc. In addition, different chemical alkali and enzymatic hydrolyses can be utilized before mechanical processes in order to promote the accessibility of hydroxyl groups, increase the inner surface, alter crystallinity, break cellulose hydrogen bonds, and therefore boost the reactivity of the fibers.
The mechanical treatments can isolate CNF from the primary and secondary cell wall without severely degrading cellulose. For instance, microfluidization and high-intensity ultrasonic treatments produce a high shear gradients causing transverse cleavage along the longitudinal axis of the cellulose fibers, and as a result, they tend to damage the microfibril structure by reducing the molar mass and degree of crystallinity. Depending on the mechanical force levels and types of mechanical treatment, interfibrillar hydrogen bonding are broken [2, 32, 33]. However, the mechanical methods exhibit high production costs (tools and materials); they are also less efficient and require greater energy than the chemical methods [34].
For this reason, a chemical pretreatment reduces energy consumption and makes the surface more hydrophobic. Further, the mechanical treatment usually reduces the degree of polymerization (DP) from 1,200 to 1,400 to a DP between 850 and 500. A high cellulose DP is desirable since this is correlated with the nanofiber tensile strength, which can be at least 2 GPa [22, 35]
In this process, dilute slurries of cellulose fibers (2–7% w/v) are passed through a spring-loaded valve assembly, at high pressure (8,000 psi), low velocity and exposed to a pressure drop to atmospheric condition while the valve opens and closes in a cyclic motion. This results in high shear and impact forces generated in a minute gap of the valve maintained at a temperature of 70–80°C [30]. As a result, the cell wall is peeled off and the DP is reduced [35, 36]. For instance, the DP is reduced from 2720 to 740 when cotton is used as a source of cellulose. Usually, this method produces fibers with diameters between 20 and 100 nm and lengths of several tens of micrometers. However, this method present some problems such as clogging of the homogenizer, high energy consumption, and mechanical damage of the crystalline microfibril structure [34, 36, 37]. HPH also decreases the crystallinity of nanofibers by increasing the number of passes.
It is a process by which a fiber suspension is pumped through thin z-shaped chambers under a high pressure (~30,000 psi). The slurry is accelerated and led into the interaction chamber where it passes through geometrically fixed microchannels at very high velocities. Thin Z-shaped chambers with different sizes generate a high shear rate and impact forces against colliding streams. A microfluidizer generates CNFs with several micrometers in length and less than 100 nm in diameter.
This is a single process by which the cellulose suspension is passed through an ultrafine grinder where the upper stone is static and the lower stone is rotating at 1400–1500 rpm. As a result, the cell wall structure is broken down by shear forces generating a gel due to the heat generated by friction while evaporating water. However, a mechanical damage of the fiber would occur [38]. This process has been used to extract CNFs from wheat straw and soy hulls [39]. Compression is a modified grinding system by which delignified fibers of cellulosic materials are placed in a bed of stripes placed between the two plates and subjected to a constant load of 10 tons for several seconds. However, in this process fibers in the micrometer rather in the nanometer size range are obtained [40].
In this process, swollen cellulosic fibers are immersed in liquid nitrogen. These brittle fibers are subsequently crushed by high shear and impact forces. As a result, ice crystals exert pressure on the cell walls, causing them to rupture. Usually, this method produces CNFs with diameters ranging from 30 to 80 nm [3].
It is a mechanical process in which oscillating power is used to isolate CNFs by hydrodynamic forces of ultrasound [41]. During the process, cavitation leads to a formation of powerful oscillating high intensive waves. These microscopic gas bubbles expand and implode breaking down cellulose fibers. However, a large feed concentration and a large distance from probe to beaker is not advantageous for fibrillation. A typical treatment requires a cylindrical titanium alloy probe tip of 1.5 cm in diameter, high temperatures, 1000 W power, and 20–25 kHz for ~30 min [42].
It is a thermomechanical process (200–270°C) that exposes cellulose to a high pressure of steam (14–16 bar). As a result, it penetrates the biomass by diffusion for short periods of time (20 s to 20 min), followed by a sudden decompression (explosion) generating shear forces which hydrolyze the glycosidic and hydrogen bonds between the glucose chains [31].
All the above-described mechanical methods demands a high energy consumption (20,000–30,000 kWh/tonne), which prevents their successful commercialization. Therefore, by combining the mechanical treatment with enzymatic or chemical pretreatments, it is possible to decrease the high energy consumption.
Conventional treatments to obtain cellulose nanoparticles.
In this electromechanical method, a cellulose dispersion is extruded and electrospun under the effect of a high electric field. Thus, a charged stream of cellulose dispersion is ejected following a 3D spiral trajectory. Once the solvent evaporates, it leaves behind a randomly oriented nanofibers in the collector [43]. This is a quite simple and cost-effective process. The morphology of the CNFs produced by this technology depends on factors such as the electric field strength, solution feed rate, tip-to-collector distance, etc. [43].
In this treatment, an enzyme is used to modify and/or degrade the lignin and hemicelluloses, while preventing the cellulose region. These enzymes are produced by cellobiohydrolases, which are A- and B-type cellulases able to attack the crystalline portion of cellulose, and endoglucanases C and D type, which are able to attack the disordered structure (amorphous) of cellulose [12]. Cellobiohydrolases and endoglucanases have strong synergistic effects. Thus, pretreated fibers subjected to the lowest enzyme concentration (0.02%) disintegrate, while molecular weight and fiber length are preserved. Endoglucanases cleave the noncovalent internal bonds, whereas exoglucanases attack the terminal glycosidic bonds [44]. Furthermore,
CNCs are commonly isolated from cellulose fibers by acid hydrolysis. Tunicin is a cellulose extracted from sea animal sources made up of highly crystalline nanofibers and has an helical organization. It has a high modulus, a high aspect ratio, and good compatibility with matrix materials [45]. This cellulose is obtained by cutting into small fragments followed by bleaching. Subsequently, CNC is extracted from bleached samples by acid hydrolysis with 64 v/v% H2SO4, for 5 h, at 50°C. Typically, the diameter, the length, and the aspect ratio of CNC are 4–25 nm, 100–500 nm, and 15–50, respectively. Among the many cellulosic sources used for its isolation, cotton constitutes the main source. It exhibits an elongated crystalline rodlike shape and has a limited flexibility since it has no amorphous regions. These CNC have a degree of crystallinity from 55% to 90%. Moreover, the degree of crystallinity, aspect ratio, and morphology depends on the source of cellulosic material and preparation conditions [46].
A typical production process involves acid hydrolysis, washing, centrifugation, dialysis, and sonication to form a suspension followed by drying [47]. The main process for the preparation of CNCs is based on strong acid hydrolysis under strictly controlled conditions of concentration, temperature, agitation, and time. The mineral acid breaks the
For instance, hydrolysis with 63.5 v/v% H2SO4 for 2 h leads to a 30% yield, a width narrower than 10 nm and length ranging between 200 and 400 nm [3]. Smaller CNCs are obtained by increasing hydrolysis time and acid concentration [15]. Another treatment employs wood pulp boiled with 2.5 N sulfuric acid for 12 h, generating CNCs with lengths between 50 and 60 nm and widths between 5 and 10 nm [49].
The physical characteristics of CNCs depend on the origin of cellulose sources, concentration of acid, types of acid, reaction time, and temperature [3]. If sulfuric acid (50–70% w/v), temperature of 20–70°C, rate of 500 rpm, and time of 0.5–6 h are employed, esterification also occurs forming “cellulose sulfate,” resulting in a negatively charged surface on the cellulose crystallites. Longer hydrolysis time and higher temperature generate shorter nanocrystals with higher surface charge, high crystallinity (~80%), and narrower polydispersity [50–53]. However, the very limited commercial availability of CNC is due to the time consuming production process and the low yield produced, especially if the initial amount of amorphous cellulose is very high. The aggregation of CNC occurs with HCl, but sulfuric acid creates charged sulfate esters promoting the dispersion of the CNCs in water preventing aggregation. The combination of both sulfuric and hydrochloric acids during hydrolysis generates spherical nanoparticles with improved thermal stability due to the reduced presence of sulfate groups on their surface. The negative surface charge of CNCs stabilizes the aqueous suspension against flocculation, but this charge also compromises the thermostability of nanocrystals. Therefore, the increase in the sulfate group content decreases the temperature at which thermal degradation takes place [54]. CNCs also exhibit chiral nematic liquid crystalline alignments, which are seen as a flow of birefringence between two crossed polarizing films.
The aim of the pretreatment process is to remove ashes, waxes, lignin, hemicellulose, and other noncellulosic compounds, which are crucial to produce pure cellulosic products such as CNFs and CNCs [30–32]. A pretreatment also reduces the energy demand of mechanical processes from 20,000 to 30,000 kWh/tonne to 1000 kWh/tonne. The types of pretreatments applied on different raw materials such as tunicate, algae, and bacteria cellulose have been reported previously [21, 55]. The alkaline delignification and organosolvation with acetic acid, aqueous methanol, or ethanol are also considered as pretreatment processes [56, 57].
Alkaline treatments are conducted when a more effective lignin, hemicellulose, and pectin solubilization and removal is needed. Alkaline extraction needs to be controlled to avoid cellulose degradation [3]. A typical treatment involves dipping of fibers in a 5% sodium hydroxide solution for ~48 h at 30°C. At pH >12, NaOH reduces super oxide radicals (-O2), wherein lignin and hemicellulose are hydrolyzed [15]. However, if lignin content is high in the cellulosic source, the nanocellulose yield is low [15, 58].
Pulp can be bleached to improve ageing resistance avoiding yellowing and brittleness. These two defects are mainly related to the presence of lignin. Different compounds are commonly used for bleaching. These include hydrogen peroxide (H2O2), chlorine dioxide (ClO2), ozone (O3), peracetic acid, and NaClO2. Sulfite pulps are more readily bleached and results in high yields [59]
The TEMPO-mediated surface oxidation is the most commonly used chemical pretreatment conducted under aqueous and mild conditions. It converts the primary hydroxyl group (C6) to a charged aldehyde or carboxylate functional group, whereas the secondary hydroxyl moieties present in the cellulose molecule remain unaffected [1, 12]. The oxidation of cellulose fibers occurs in the presence of NaClO and catalytic amounts of 2,2,6,6 tetramethyl-1 piperidinyloxy radical (TEMPO) and NaBr as catalyst at a pH between 9 and 11 and room temperature. The higher the amount of NaClO in the reaction medium, the larger is the number of carboxylic groups formed at the surface of the CNFs and the stronger is the decrease in DP [44]. This oxidation creates negative charges on the surface of CNC [31] without changing the original fibrous morphologies [61–66]. The reaction by-product is only sodium chloride. Other N-oxyl compounds, such as the 4-hydroxy TEMPO derivative (less expensive than TEMPO), have been proposed. The residual aldehyde groups causes discoloration. In order to avoid depolymerization or discoloration of the oxidized cellulose, a TEMPO/NaClO/NaClO2 system is employed under neutral or slightly acidic conditions [60]. This treatment also prevents the postaggregation of nanoparticles during the drying step.
A variation of this condition oxidizes wood cellulose rendering CNF with a higher molecular weight and with no aldehyde groups using a TEMPO/NaClO/NaClO2 system at pHs ranging from 5 to 7 [67]. The TEMPO pretreatment eases the separation of the nanofibrils from each other due to the repulsive forces of the ionized carboxylate groups, which overwhelm the hydrogen bonds. The TEMPO oxidation pretreatment is usually followed by a mechanical treatment. Other less commonly used processes include oxidation at 60°C with ammonium persulfate and the sequential periodate and chlorite oxidation [68].
Ionic liquids are organic salts having no corrosive properties, no flammability, a melting point below 100°C, low vapor pressure, and low viscosities [34]. Ionic liquids dissolve cellulose and render a wide range of particle morphologies after precipitation. The ionic liquid breaks intramolecular hydrogen bonds, whereas the cations attack the O atom of the –OH, and anions attack the hydrogen atoms of the -OH group [34]. PF6-, BF4-, (CF3CO2)-, (SbF6)-, (OTS)-, (ClO4)-, (GeCl3)-, (Al2Cl7)-, and (AlCl4)- are the most common anions employed [69, 70].
This chemical treatment is performed on the surface of BC, CNC, or CNF for making them more hydrophobic reducing the agglomeration tendency of these materials. The goal of the derivatization is to endow nanocellulose with a hydrophobic character in order to improve its compatibility with nonpolar polymers [60, 71–73].
This process makes the surface negatively charged, promotes the formation of a stable suspension, and increases the breakup of lignocellulosic fibers [2]. If carboxymethylation is conducted before mechanical treatment, the fibers become more dispersible having a lower degree of crystallinity [72].
In this reaction, the C6 hydroxyl groups of cellulose are selectively converted to carboxylate groups and only NaClO and NaOH are consumed. The amount of carboxylate groups formed increases with the amount of NaClO and by employing long reaction times [74]. This reaction causes plasticization of lignocellulosic fibers [31] [54]. Further, a reaction of CNF with acetic anhydride at 105°C for 30 min causes a degree of substitution (DS) of 0.43. As a result, the contact angle increases from 33° for nonacetylated nanofibers to 115° for acetylated ones. The acetylated fibers have a lower crystallinity due to degradation of crystalline regions during the reaction.
Isocyanates, in particular, octadecyl isocyanate, can generate covalent bonds with hydroxyl groups on the particle surface, rendering a degree of substitution of 0.07 and 0.09 for CNC and NFC, respectively [75].
The reaction between silanol and OH groups of cellulose at high temperature is initiated by water. Surface silylation of CNFs from bleached softwood pulp using chlorodimethyl isopropylsilane renders a degree of surface substitution from 0.6 to 1. Conversely, silylation of CNFs by isopropyl dimethylchlorosilane renders a CNF that forms suspensions with a shear-thinning behavior [54].
Depending upon the source of the cellulose and the method of production, a CNF displays similar morphologies but several dimensions. Typically, a CNF and a CNC have typical diameters of 2–100 nm and between 2 and 30 nm, respectively. For instance, CNFs from wheat straw have diameters from 10 to 80 nm [22] as compared to soy hulls (20–120 nm) [20], kenaf bast (2–6 nm), wood (15 nm), bagasse (5–15 nm), rice straw (4–13 nm), soybean stock-based (50–100 nm), cotton (10– 25 nm), and empty fruit bunch (10–30 nm) [31, 76–85].
Crystallinity is highly dependent on the lignocellulosic source. For instance, crystallinity of flax, rutabaga, and wood CNFs are 59%, 64%, and 54%, respectively, whereas a crystallinity of 85.9%, 76%, 84.9%, 94%, 80.6%, and 81.7% has been found for CNCs obtained from sisal, rice husk, flax, cotton, corn stover, and commercial MCC, respectively. On the other hand, a DC of 78% and 70% has been obtained for wheat straw [22] and soy hull CNFs, respectively. Further, very low values have been obtained for beet pulp ~30–40% [20]. The degree of crystallinity ranges in the order: pineapple > banana > jute, and this order agrees with the values of cellulose content determined in these samples. Usually, CNCs prepared from H2SO4 have lower crystalline values than those prepared from HCl. In addition, the increase in hydrolysis time also increases crystallinity due to the elimination of amorphous regions [15].
The thermal degradation of lignocellulosic materials begins with an early decomposition of hemicelluloses, followed by an early stage of pyrolysis of lignin, depolymerization, active flaming combustion, and char oxidation. Further, CNF has a high degradation temperature onset (350°C) and better thermal behavior than hemicellulose, pectin, and lignin. On the contrary, the onset of the thermal degradation of CNC typically occurs at 200–300°C[86]. CNC with lower sulfate content have better thermal stability [53]. On the other hand, banana CNF exhibited three main weight loss regions. The initial weight is mainly due to moisture evaporation followed by thermal depolymerization of hemicellulose and the cleavage of glycosidic linkages of cellulose. The broad peak in the region from 200°C to 500°C is due to residual lignin components. A convection drying of a CNF removes water slowly causing the formation of aggregates. Therefore, the dried CNF presents a lower degree of thermal stability than that of the original fibers. [19].
DP is strongly correlated with the aspect ratio of the nanofibers. As explained previously, any pretreatment process also reduces the DP. On the other hand, the mechanical properties of cellulose nanoparticles depend on morphology, geometrical dimensions, crystal structure, crystallinity, and the process used to produce CNCs and CNFs. For instance, the DP of softwood is 2249, but the DP of sulfated CNF is 825. Further, the tensile strength of native CNCs ranges from 7.5 to 7.7 GPa. Further, the Young’s modulus of CNCs is estimated to lie between 130 and 250 GPa.
Drying of individual cellulose nanoparticles creates irreversible agglomeration affecting their dimension and, therefore, their unique properties [87]. This irreversible agglomeration is known as hornification and is related to the hydrogen bonds formed [81]. If freeze-drying or supercritical dying with CO2 is used, agglomeration is avoided [87–89].
CNF gels can be diluted and either cast or vacuum filtered followed by drying to form stiff films due to the formation of an interfibrillar hydrogen bonding network [63, 90–93]. For instance, CNF films obtained from sugar beet have values of tensile strength and modulus of 104 MPa and 3.5 GPa, respectively [37, 61, 94].
Cellulose nanoparticles have a high specific surface area (SSA). Typically, cellulose nanoparticles have SSA ranging from 50 to 200 g/m2. Conversely, the SSA of nanocellulose aerogels ranges higher from 250 to 350 m2/g and have a very low density (0.02 g/cm3) and a high porosity of 98% [61, 63, 94].
CNF suspensions exhibit a shear-thinning behavior and pseudoplasticity, which in turn depends on the pH medium [95]. Further, sulfate cellulose shows a pH-dependent viscosity profile due to electrostatic interactions. Moreover, a CNF suspension has a decreasing viscosity with increasing shear rates. Further, CNF also has a high elastic modulus due to the entangled network structure [96].
CNFs are able to form films with a low moisture diffusivity due to a rigid fiber network [90] and, thus, have excellent barrier properties [90]. The water vapor transfer rate (WVTR) of CNFs films are 20% smaller than those made of macrofibers (from 20% to 30%). CNC films are expected to provide a better barrier to water since CNC films have a more crystalline nature than CNF [90].
The oxygen transmittance rate of CNF at 0% RH is in the range 17–18 mL/m2/day. The increase of RH increases the oxygen permeability due to the limited hydrogen bonding and loose network caused by the incoming water molecules. The water and oxygen permeability decreased with increasing film thickness due to the lack of interconnectivity of pores [63].
CNCs have low toxicity and low environmental risk according to ecotoxicological tests with several aquatic species (e.g., Daphnia, rainbow trout and fathead minnow). Further, cytotoxicity (intracellular toxic effect) and proinflammatory response are significantly lower than those for MWCNT (multiwalled carbon nanotubes) and CAF (crocidolite asbestos fibers). CNF shows no toxicity and genotoxicity in vitro [97]. The toxicity of BC nanofibers has been successfully evaluated in vitro through cell viability and flow cytometric assays and in vivo using C57/B16 mice surgeries. Further, BC shows no toxicity in human umbilical vein endothelial cell culture, fibroblasts, and chondrocytes. The in vitro evaluation also shows that 95% of the mesenchymal stem cells aggregate to cellulose membrane [98, 99] (Fig. 3).
Nanocellulose has been mainly used as a filler in nanocomposites because of its good mechanical properties due to their biodegradability, renewability, availability, sustainability, lower cost, lower weight, higher mechanical strength, biocompatibility, high hydrophilicity, and high surface area [94, 100, 101–105]. It evades adverse tissue reactions, and unlike proteins, its polysaccharide nature makes it less immunogenic and nonhemolytic. It also promotes cellular interaction and tissue development. It is a slow/nondegrading material in vivo and in vitro, which makes it suitable for use as a scaffold providing a long-term support, sustains high loads, and has a high wear resistance. The biomedical industry includes skin replacements for burnings and wounds; drug releasing system; blood vessel growth; nerves, gum, and dura mater reconstruction; scaffolds for tissue engineering; stent covering; and bone reconstruction. The cellulose nanoparticle surface dictates cellular response by interfering with cellular adhesion, proliferation, migration, and functioning. On the other hand, cells support, hold, synthesize the matrix for the new tissues, and keep the proper growth ambient, whereas the growth factors promote the cell regeneration [97, 101, 106, 107].
In one study, a charged CNC–FITC and newly synthesized CNC–rhodamine B isothiocyanate (RBITC) were synthesized, and in vitro cellular uptake studies showed that the positively charged CNC-RBITC was taken up by human embryonic kidney (HEK) and
Biomedical applications of cellulose nanoparticles.
CNFs serve as a suitable platform for immobilization of bioactive molecules (e.g., enzymes, antibodies, etc.), which is useful in biosensors and diagnostics. For example, novel gold bacterial cellulose (Au-BC) nanocomposites have been prepared by a one-step biotemplated method in aqueous suspensions. This material shows excellent biocompatibility, good conductivity, and ultrafine nanofiber network structure, which makes it able to entrap horseradish peroxidase (HRP), maintaining enzyme bioactivity. HRP biosensors allow detection of H2O2 with a detection limit lower than 1 μM [109]. CNF films carboxlylated with TEMPO and activated via EDC/NHS coupling have been used to immobilize the antibody (antihuman immunoglobulin G (anti-IgG)) by physical adsorption. This surface can detect positively charged molecules. A TEMPO-activated film has also been used to conjugate Avidin for selectively capturing biotinylated molecules (anti-IgG) [109, 110].
Another study showed CNF to prepare support films with carboxyl groups, which are then converted to amine-reactive species. These substrates were then used to bind polyclonal anti-IgG. The CNF surface can also be activated by copolymer grafting. Thus, a peptide with specific affinity to human IgG is conjugated to the grafted polymer having a high selectivity.
Proteins such as collagen, elastin, hyaluronan, and growth factors such as the basic fibroblast growth factor (B-FGF), human epidermal growth factor (H-EGF), and keratinocyte growth factor (KGF) have been immobilized on macroporous BC to improve biocompatibility. The attachment of cells can be improved by utilizing adhesive amino acid sequences, such as Arg-Gly-Asp (RGD) found in several extracellular matrix proteins [111, 112].
Peptides such as the HWRGWV peptide can be immobilized on the TEMPO-activated film to detect human IgG. Thus, the acetylated peptide is covalently immobilized to the spacers on CNF via amide reaction. For instance, chitosan can be physically adsorbed onto the CNF and used as a spacer. The resulting biosensor has a very high specific binding capability for IgG and exhibits excellent resistance for nonspecific protein adsorption [113]. In another study, Edwards et al. created biosensors based on CNC by peptide conjugation for detection of human neutrophil elastase [114].
On the other hand, CNCs have been used as electrochemical sensors to selectively detect DNA hybridization. DNA oligomers were grafted onto TEMPO-oxidized CNC produced from cotton. This DNA-grafted CNC is able to self-assembling into larger aggregates as compared to the unmodified CNC. In another study, silver nanoparticles were obtained onto TEMPO-mediated oxidized CNC by using NaBH4 as a reducing agent. The presence of CNC prevented the aggregation of the nanoparticles [115].
Moreover, the layer by layer (LbL) assembly technique has been used to adsorb collagen onto the surface of CNF. The LbL technique has also been used to prepare a luminescent single-walled carbon nanotube–CNC films enhancing their water dispersibility [116].
Dong et al. synthesized folic acid (FA)-grafted CNCs and explored their folate-receptor-mediated uptake by human and rat brain tumor cells. First, CNCs were labeled with fluorescein isothiocyanate (FITC) for detection in the cells and were then conjugated with FA. In vitro studies showed that the cellular binding of the FITC–CNC–FA by the folate receptor (which is overexpressed by cancer cells) was higher than that of the free FA [117].
Nanocellulose membranes could serve as an infection barrier, prevent loss of fluids, have a painkiller effect, allow drugs to be easily applied, and also absorb the purulent fluids during all inflammatory stages, expelling them later on in a controlled and painless manner [118].
Properties such as biocompatibility, high superficial area, high water absorption capacity, high elastic modulus, low thermal expansion coefficient, optical transparency, anisotropy, and flexible surface chemistry endow nanocellulose with suitable wound dressing applications. For instance, a membrane has been developed with BC and propolis extract, rendering antimicrobial and anti-inflammatory activities in chronic wounds absorbing purulent exudates. Further, it eases the BC removal from a wound surface after recovery [97].
Traditionally, skin tissue repair materials have been absorbent, permeable materials such as gauze, which can adhere to desiccated wound surfaces inducing trauma upon removal [119, 120]. BC controls wound dressing since it can control wound exudates and can provide a moist environment to a wound resulting in better wound healing. For instance, Biofill® is a commercial product of BC used as a temporary substitute for human skin in cases of second and third degree burns.
Czaja et al. showed that the skin of the patients whose burns were covered with a BC membrane healed faster than the wounds of patients who received conventional wound dressings. This is explained by the faster tissue regeneration, capillary formation and cell proliferation [121].
In a different study, BC wound dressing materials were compared to two different commercial dressings, Vaseline gauze, and Algisite M in a rat model. This study showed that BC-dressed animals had more rapid wound healing within 14 days without any evidence of toxicity [122]. Further, BC, gelatin, and alginate composite membranes showed the successful growth of NIH/3T3-type cells and, hence, proved potential as a skin tissue regeneration template [123].
The addition of chitosan to a tempo-oxidized BC renders a composite with high superior mechanical properties, water holding capacity, and water release rate, and thus, these composites can be used for wound dressing [124].
BC has also been used in a surgery of the lateral wall of the nose preventing nasal bleeding, surgical wound infections, local pain, and clotting [125]. Therefore, it provides a more rapid healing without the formation of crusts and prevent infection without the need for removal as compared to commercial nasal packing which causes a great discomfort upon removal [125].
A nanocellulose membrane has also been implanted into the subcutaneous tissue of diabetic rats for 12 weeks. Rats showed no macroscopic signs of inflammation around the implants, no formation of fibrotic capsule or giant cells, and fibroblasts were fully integrated to the cellulosic membrane and started to synthesize collagen [126].
Neural interfaces are able to record neural signals from individual neurons or small groups of neurons in the brain. The most common neural interfaces are made of iridium oxide, silicon, platinum, titanium, glassy carbon, gold, and stainless steel. However, they cause glia encapsulation at the electrode interface, leading to neuron death near the surface of the implanted electrode. For this reason, adaptive cellulose nanoparticles interfaces should be stiff enough to be easily implanted into the brain but subsequently soften under in vivo conditions to closely match the stiffness of the brain tissue.
This nanocellulosic interface relies on stiff collagen fibers dispersed throughout a soft fibrillin matrix. Because of the abundance of surface hydroxyl groups, CNCs strongly interact with each other through hydrogen bonding and/or van der Waals’ forces, but exposure to water reduces CNC–CNC interactions because of competitive hydrogen bonding or interfacial interactions with intermolecular van der Waal’s forces. For instance, CNCs isolated from tunicate sea creatures have been successfully integrated into a rubbery ethylene oxide-epichlorohydrin copolymer matrix having a lower stiffness than conventional electrodes [127].
Another study reported the development of poly(vinyl acetate) (PVAc) and CNCs composites showing a dual responsive behavior. Upon exposure to physiological conditions, the composites are plasticized and the CNC network loses its stiffness capabilities due to the loss of hydrogen bonding. Once these composites were implanted in the pia mater of the cerebral cortex of a rat, the initial stiffness rapidly decreased matching that of the brain tissue [128, 129]. These adaptive microelectrodes implanted into a rat cortex for 8 weeks increased the cell density at the electrode–tissue interface. After 16 weeks of implantation, there was no neuron death surrounding PVAc/CNC implants as compared to PVAc-coated microelectrodes [130]. Another cortical implant in rats containing CNC/PVA and curcumin showed that after 4 weeks, curcumin promoted higher neuron survival and a more stable blood–brain barrier than the neat PVA controls [131].
BC-based implants have been developed to replace synthetic by-pass implants made of polytetrafluoroethylene, poly(ethylene terephthalate), polyethylene, and polyurethane. Further, BC tubes have been successfully used to replace carotid arteries in rats, pigs, and sheep without any rejection after 4 weeks [127].
One study showed that the mechanical properties of CNC-PVA composites are similar to that of cardiovascular tissues, such as aorta and heart valve leaflets. For instance, the stress–strain properties for porcine aorta and heart valve tissue matches those of PVA-nanocellulose composites in the circumferential and the axial tissue directions [132].
The nanocellulose implants have been attached in the carotid artery of rats for 1 year, resulting in incorporation nanocellulose forming neointima and ingrowth of active fibroblasts. In another study, the grafts were used to successfully replace the carotid arteries of pigs [133]. Further, cellulose and chitosan composites have been successfully used to produce hollow tubes with a compliance compared to that of human coronary arteries showing potential for coronary artery bypass graft applications [134].
In one study, part of the carotid artery (4–6 mm) of a rat was replaced using BC and after 4 weeks, the BC complex was wrapped up with connective tissue and was infused with small vessels [28, 135]. BC porous surfaces have also been reported to maintain fiber network arrangement viable in endothelial cells for 20 days [136]. Further, the surface modification of BC by nitrogen-containing plasma improved cell adhesion and proliferation of the endothelial and neuroblast cells [137].
Medical implants must have mechanical characteristics as the tissue it replaces. It must also show nonthrombogenicity, sterilizability, durability, lesser degree of calcification, and good processability. The implant should be biocompatible with the host tissues in terms of chemical, mechanical, surface chemistry, and pharmacological properties.
BC is a good candidate for use as medical implants since it is nondegradable under physiological conditions and provides durable mechanical properties and chemical stability. One study showed that the mechanical properties of the BC gel with collagen meniscal implants were similar in magnitude to the ones of pig menisci [138].
Further, an ear-shaped BC prototype material showed suitable mechanical properties for ear cartilage replacement for a customized patient-specific ear shapes [139].
A nanocellulose membrane has also been implanted in the nasal dorsum of 22 rabbits as an excellent substitute of bone cartilage. After 6 months, residual inflammation was attributed to the surgical procedure itself and not to the cellulosic membrane [140].
The cartilage that covers the trochlear groove in dogs is composed of chondrocytes. Further, BC was utilized successfully in experimental trochleoplasty in dogs, showing advantage in respect to conventional treatment for osteochondral injuries [141]. Moreover, BC membrane was applied in the tissue formation of fibrocartilage ripe, resulting in a good integration of the newly formed tissue.
Other researchers have successfully incorporated BC and polytetrafluoroethylene (PTFE) membranes in rats to correct abdominal wall defects [142]. Further, BC implanted in the peritoneum of dogs formed an integrated net along the conjunctive tissue after 6 months [143].
On the other hand, the biggest challenge in dental applications is the loss of alveolar bone. For this reason, synthetic hydroxyapatite (HAP-91) was implanted in the dental cavities and covered by nanocellulose membranes. Nanocellulose promoted faster bone regeneration and resembled those of the original tissue after 50 days [144].
A bandage product derived from BC (Gengiflex®) restores the osseous defects. It consists of an inner layer of microbial cellulose, which offers rigidity to the membrane, and an outer layer of alkali cellulose. A greater amount of bone formation was present in bone defects protected by the BC membrane, when compared to the control sites [145, 146].
BC membranes were tested as physical barriers used to treat bone defects. In this scenario, two osseous defects (8 mm in diameter) were performed in each hind foot of four adult rabbits. After 3 months, the bone defects showed lamellar bone formation resulting in partial bone deposition [147].
The asymmetric structure of a scaffold is composed of a fine network of nanofibrils, which is similar to a collagen network, which promotes the adhesion and proliferation of muscle cells [97, 101]. BC has shown significantly higher levels of chondrocyte growth, suggesting the potential application of scaffolds for cartilage tissue engineering [148]. The beneficial properties of CNF are based on its unique nanofibrillar structure, mimicking properties of the extracellular matrix, and thus, a CNF scaffold promotes hepatocyte 3D cell culture without added bioactive components.
Nanocellulose and hydroxyapatite (HA) are both capable of bone replacement because of their properties, including biocompatibility with the human body, bioactivity, osteoconductivity, and noninflammatory properties [74]. Further, nanocellulose has also been soaked into HA to develop a composite scaffold for bone regeneration. Thus, CNC/HA scaffolds were prepared by absorption of HA onto the BC surface to induce nucleation of calcium-deficient HA. The presence of calcium-deficient HA crystals on the BC surface increased cell attachment and alkaline phosphatase activity on bone cells. Further, nanocellulose has been combined with polyacrylamide and gelatin, yielding hydrogels with improved toughness [149].
Moreover, enzymatically modified gelatin (EMG) and nanocellulose composites have been prepared to improve the rehydration properties and, thus, can be used as scaffold for the cornea tissue since the stromal cells are able to grow into the scaffold [150].
In one study, BC and poly(3-hydroxubutyrate-co-4-hydroxubutyrate) (P(3HB-co-4HB) composite scaffolds showed excellent biocompatibility in Chinese hamster lung (CHL) fibroblast cells [151]. Further, the BC and alginate composite (80:20 w/w) dried by supercritical carbon dioxide formed a nanoporous structure, which supports the proliferation of keratinocytes and gingival fibroblasts [152, 153].
In another study, nanocellulose/PEG composite scaffolds were prepared by soaking a nanocellulose hydrogel with a PEG solution forming scaffold with improved thermal stability. Results indicated that the Young’s modulus and tensile strength tended to decrease while the elongation at break had a slight increase. Thus, the prepared nanocellulose/PEG composite scaffolds were suitable for cell attachment [154].
The functionalization of the BC surface with recombinant proteins containing a bioactive peptide (IKVAV) and a carbohydrate-binding module (CBM3) has improved their biocompatibility with neuronal and mesenchymal cells [155]. BC cross-linked with heparin is able to prevent the formation of blood clots [156]. A natural peptide called as polylysine (PLL) has been cross-linked to the surface of BC resembling the collagen fibers and composition of natural bone [157].
CNCs have been coated with 2-hydroxyethylmethacrylate and methacrylic functional groups forming hydrogels with excellent mechanical properties comparable to articular cartilage with hydrogel-like properties [158].
One study reported the creation composites based on BC and type I collagen (COL) for potential bone tissue engineering, in which collagen was covalently introduced into the BC network. Further, cell culture with osteogenic cells revealed that collagen did not affect cell adhesion and proliferation or its morphology [159]. Heparin and nanocellulose scaffolds have been prepared with anticoagulant properties for potential use in vascular tissue engineering [160].
Further, grafted zwitterionic carboxybetaine improved CNF membrane blood compatibility. In another study, dialdehyde BC membranes supported the epidermal cell adhesion and proliferation [161].
BC has also been used to treat wounds in diabetic foot ulcers. The mean time for 75% epithelization was achieved in 79 days, and BC shortened the epithelization time as compared to XeroformTM® Petrolatum gauze [162]. Another study showed a complete closure of the facial wound within 44 days with no significant signs of extensive scarring [121]. Further, the release of BC dressing from the wound is a painless operation due to the moisture still present in the cellulose structure [163].
A nanogel made of poly(
Nanocellulose intrinsically does not possess any antimicrobial property. Therefore, it needs to be functionalized with antimicrobial agents. For instance, chemical grafting of aminoalkyl groups [165], 2-benzyl-4- chlorophenol [166], and L-cysteine [167], onto the surface of the cellulose backbone has been reported [168]. In one study, a BC film was soaked in a benzalkonium chloride solution, resulting in antimicrobial activity against
The electrospun composite nanofiber membrane containing bis(
The immersion of BC in a silver nitrate solution, followed by reduction of absorbed silver ions (Ag+) with sodium borohydride, formed metallic silver nanoparticles with antimicrobial activity against
In another study, composites of CNF and chitin nanocrystals formed a 3D network with bactericidal activity against
In one study, BC was first homogenized with a ferric and ferrous salt mixture followed by soaking in dopamine and silver nitrate solution. The resulting magnetic silver/BC nanocomposites had antimicrobial activity against
The abundant surface hydroxyl groups in nanocellulose provide a site for the surface modification by a variety of methods. Surface modification modulates the loading and release of nonionized or hydrophobic drugs that would not normally bind to nanocellulose. For instance, poly(caprolactone) chains might be conjugated onto CNC for drug release [31].
PVA and methyl cellulose form aninterprenetrating polymer network through cross-linking with epichlorohydrin and serve as a carrier to load a drug for controlled release [31]. Further, coating of CNC with a cationic surfactant such as cetyltrimethylammonium bromide (CTABr) has been useful to load significant quantities of anticancer agents for controlled released [177–179]. In one study, nanoparticles of itraconazole were stabilized by the nanostructured cellulose matrix during freeze-drying and storage increasing its dissolution rate and in vivo performance [177].
On the other hand, spray-dried CNFs were produced in order to increase the long-term stability of drugs due to a better ability to pack having a low porosity and forming fast disintegrating tablets [179]. Further, BC membranes loaded with lidocaine rendered lower permeation rates in the skin than traditional drug delivery systems. The greatest advantage of the BC membrane is the combination of its wound healing capacity and the ability to absorb exudates with the release of antimicrobial and anti-inflammatory drugs [180].
In another study, freeze-dried BC and serum albumin composites were investigated as potential drug delivery systems for proteins [110]. In one report, CNC was oxidized with periodic acid to graft a spacer molecule (aminobutyric acid), and then syringyl alcohol was attached. In another investigation, calcium peroxide (CPO) was embedded into highly porous CNCs to produce H2O2, whereas catalase was added to convert the generated H2O2 to O2, increasing cell survival up to 5 days [181].
Weng et al. created biodegradables cellulose microspheres loaded with doxorubicin for arterial embolization applications. They showed a burst release profile within 8 h followed by a release plateau over a 24-h period in rabbits [182].
Further, docetaxel-loaded CMC-based nanoparticles have been produced for enhanced cytotoxicity against cancer cells releasing 100% of drug within 3 weeks inhibiting 90% of tumor growth [183]. In another study, CMC gels were produced by polymerization of oligo(ethylene oxide)-methacrylate (OEOMA) in the presence of CNC. These gels have a dual drug release in response to acidic pH and thiol-reducing agents [184].
Zoppe and collaborators applied CNC-based systems as viral inhibitors (alphavirus infectivity) and suggested that CNC can be used for inhibition of HIV [185].
The attractive properties of nanocellulosic materials such as biodegradability, biocompactibility, renewability, low density, high strength, good stiffness, low thermal expansion, and high aspect ratio make them suitable for biomedical applications. For this reason, the number of publications and patents related to these applications has skyrocketed in the last 5 years. However, a great effort has still to be made to reduce the high cost involved with the production process of nanocellulose intended for biomedical used.
What is human error and how can we learn from them?
According to UK hospital literature data, at least one in ten patients is certain to suffer some level of harm during their care [1]. If true, it is a terrifying proposition, resulting in about 600,000 incidents per year in Great Britain alone. This is in comparison to the aviation industry, where fatalities have never exceeded 0.6 cases per million flights (14 deaths) [Civil Aviation Authority]. In the aviation sector, each incident must be investigated by law, however, there are no similar legal obligations for health care providers despite the significantly higher numbers of incidents and fatalities.
How can we improve healthcare related harm? Shall we introduce additional protocols and checklists similar to practice ibn the aviation sector? Does each complaint or error need a thorough analysis to better understand what could have led to the incident at both individual and organisational level? Is this data applicable to different health care systems or UK specific? If this proportion of harm is not country specific, how can we learn from each other?
The authors opine that there is no single good answer, but rather a series of answers, which together can help to understand and solve the problem of accidental, preventable harm in healthcare. In this chapter, we present a real-life incident and aim to guide the reader to implement both an industrial and a health care related algorithm to recognise, analyse and synthesise the learning points of the exemplary error. We also would like to spark further discussions and invite any interested readers to a best practice sharing session at the end of the chapter. We encourage everybody to join/start any blog in this topic to spread the word about the importance of learning from errors in health care.
The fast pace of modern medicine is mostly driven by patient’s demand for a quick fix, however this tempo does not result in a faultless operation. The often-unreasonable hurry is likely one of the reasons why the emergency speciality has unfortunately claimed a silver medallist position on the podium of litigation, not far behind the surgical disciplines [2, 3]. Clearly, other factors, like the immense stress, the constant pressure to make back-to-back decisions and perform various procedures under severe time pressure are also inherently incident prone. Speed comes at a price that is mostly paid by the patient but often the health care provider as well (second victim). The other element that attracts mistakes is the number of interruptions during the process of care. A typical patient journey in the emergency department includes countless stops, each with a brief handover between providers of different qualifications (ambulance, triage nurse, doctor, etc.). Handovers are knowingly dangerous in medicine. Everyone knows the Chinese whisper when a sentence conveyed ear-to-ear in a line of people. By the time the message reaches the end, the original text is barely recognisable. Unsurprisingly, according to regulatory bodies, one of the most common errors in emergency departments is loss of data [4, 5].
Human errors are events when a planned action fails to achieve the desired result due to a human failure. In this chapter we introduce both an ergonomic based industrial approach and hospital protocols used in the UK. Both methods are excellent not only for recognising an error or even a near miss. They are also useful at mitigating consequential damage, mapping the factors leading to the incident, and also preventing possible future occurrences and instigating the necessary corrective measures (Figure 1). The explicit goal of the ergonomic approach is the optimization of equipment design and reduction of work-related stress to minimise chances of human errors (International Civil Aviation Organisation). Even though similar initiatives are seen in medicine, as of yet there is no overarching authority to enforce necessary measures.
Ergonomic flowchart for processing human omission categories.
In the UK, Australia, Canada and the USA, dedicated systems are in place to facilitate incident recognition and reporting. Most enable users to anonymously (or named) report any adverse occurrence. The systems are designed to alert manager levels and prompt actions according to pre-set protocols.
In the next paragraphs, we present an incident from a real ED (Box 1 and 2). The reader will be asked to review the incident and use their experience to work up the error as normal (according to local protocols/experience). An ergonomic flow chart will then be shown and the reader should compare the two approaches and mark their thoughts in the below workbook.
The summary of the clinical incident.
Result of the usual approach: Result of the ergonomic approach: Result of the repeated ergonomic assessment: |
The Mental Capacity Act (MCA) was designed to protect and empower people who may lack the mental capacity to make their own decisions about their care and treatment. It applies to people aged 16 and over. The MCA refers to decisions about day-to-day situations and giving consent to medical interventions including surgery. There are 5 principles of the MCA and all practitioners must act in the best interest of the patients and presume that anybody under their care has the capacity to make a decision themselves, unless it’s proved otherwise. Furthermore, any health care worker must make sure to help people make their own decisions, whenever it is feasible. In this case, despite the registrar believing to have acted in the best interest of the patient, he breached the protocols by not discussing his working diagnosis of potential postpartum depression and the steps he deemed necessary to help the patient. As the MCA states people must be encouraged “to express their preferences for care and treatment” the registrar should have discussed all available options detailing the presumed benefit and exploring the patient’s understanding of the help offered. In addition, the registrar should have assessed potential cultural barriers, as in some cases, depression (or any mental health diagnosis) might be seen stigmatising and shameful. |
In incident management, sometimes multiple answers are available for the same question. To give the benefit of doubt, the reader is asked to repeat the ergonomic exercise using the other arm of the process. If, during the above, the reader responded that the error was “Intentional Non-Compliance” (i.e., the junior doctor knowingly violated departmental regulations by failing to record vital parameters, to seek senior advice before transferring the patient and did not hand over the patient to the nurse in charge of the clinical decision unit) they should consider choosing the alternative path of “Inadvertent error/incomplete knowledge” (the junior was not aware of the regular transfer process and/or undervalued the patient’s condition). One must realise that both solutions (and even a combination of the two) are equally conceivable however, each involves different corrective steps.
The full extent of the incident.
The incident log entry said: “
Poor handover.
Records not available.
Documentation/Tracking issue.
Once an incident was recognised, the immediate harm was mitigated the background and context needs further assessment. Again, the health care approach is different to the ergonomic one. Without a detailed understanding of the circumstances and background facts, causes cannot be fully determined. Without fully exploring the causes, potential future recurrence of similar incidents cannot be prevented. Therefore, it is in the best interest of any system to learn the crucial details.
The reader shall review the below two charts (Figure 2; Table 1) and mark their ideas on risk assessment in Workbook 2.
Ergonomic flow chart for risk assessment.
Likelihood score | Rare | Unlikely | Possible | Likely | Almost certain |
---|---|---|---|---|---|
Will probably never happen/recur | Unlikely to happen again/recur, but it may do so | Might happen or recur occasionally | Will probably happen/recur but it is not a pressing issue | Will surey happen/recur possibly frequently | |
Catastrophic | 5 | 10 | 15 | 20 | 25 |
Major | 4 | 8 | 12 | 16 | 20 |
Moderate | 3 | 6 | 9 | 12 | 15 |
Minor | 2 | 4 | 6 | 8 | 10 |
Negligible | 1 | 2 | 3 | 4 | 5 |
Incident likelihood and risk scoring (risk scoring = consequence x likelihood).
Low risk = 1–3; Moderate risk = 4–6, High risk = 8–12; Extreme risk = 15–25.
Ideas generated by the ergonomic approach Ideas generated by the healthcare approach |
The UK hospital practice has currently advocated three methods to identify causation: the formal “Root Cause Analysis” (RCA), the “fishbone” approach, and the “5 - why” (5 W) method. There are no set rules as to when to implement a certain method, however, a rule of thumb is that an RCA is used to analyse complex, severe, and/or frequently recurring problems, while the “fishbone,” or 5 W method, is reserved for simpler incidents [6, 7, 8].
As in our present example, the patient did not suffer permanent health impairment and the number of involved of staff was less than 5 people. The 5 W method was used in the investigation process. The advantages of this approach are that it does not take a long time but creates an opportunity for a layered analysis. The technique is simple; the investigator should ask a minimum of 5 questions starting with “Why”. If the problem cannot be explored in depth even after the 5th question then either, additional questions can be raised or a new method is needed to investigate further. The disadvantage of the 5 W method is its subjectivity: no matter how unbiased the investigator, their cultural, cognitive, and emotional factors can affect the result. To address this source bias (if resources allow), two independent investigators are advised to be put on the case. Given the length of the article, the fishbone and RCA approach cannot be presented at this time, however, the reader is encouraged to review these methods based on the references provided.
The reader is asked to formulate their own 5 questions and enter in the workbook. Once finished, please review the questions raised by the hospital investigator (see Table 2). Compare the questions and make notes of the differences. What does the difference suggest to the reader?
Question | Answer |
---|---|
As the patient presented with the same complaints twice (unplanned return), per department policy she should have been seen by a consultant. The night shift was very busy, the consultant on call was unavailable, therefore the night registrar admitted the patient to the CDU. | |
The patient was seen by two different juniors and the case was discussed with two different seniors. There was no mention of the social or mental health assessment as the juniors did not think about it. | |
The registrar was very busy with other patients and thought that once spoken to by someone from the Crisis Team he will discharge the patient with a home appointment with a counsellor. | |
The Crisis Team assessed another patient at the medical ward and thought to that they would quickly see the patient. | |
The patient was seen by the Crisis. Team and as she refused any further intervention (she felt offended by the stigmatising label of depression) the CDU charge nurse offered her a self-discharge form. By the time the registrar returned to review, the patient had left. |
Summary of the investigators “5-whys” of the above error.
Table 2 Summary of the given clinical incident according to the 5 W method.
Question 1. Question 2. Question 3. Question 4. Question 5. The differences between the readers and the investigators questions: 1. 2. 3. 4. 5. Please reflect on the differences |
The previous paragraphs helped the reader to review a real-world, potentially dangerous incident, identify the involved parties, have a detailed background check, categorise the error leading to the incident, perform a quick risk assessment, and address immediate threats. In the next section, we will determine the learning points and decide who shall learn to prevent further occurrences.
This is a key step in the process, as the severity of any particular incident is determined by the weight of the consequences and the frequency of potential reoccurrence. These evaluation steps will also reveal the nature of necessary corrective actions on both an individual and organisational level. In Anglo-Saxon areas, health care institutions use a very similar nomenclature/protocols for reporting incidents: minor events (“near miss”, “quasi-damage”, or “minimal damage”) should only be reported to the immediate supervisor (as is practical, but preferably within 12 hours), whose task it is to investigate, resolve or take it forward. However, moderate/severe incidents should be reported immediately not only to the line manager, but the director in charge. In most cases, the reporting system automatically notifies the appropriate level. “Serious” or “catastrophic” events should be immediately taken to the hospital directorship level. The reader is asked to review Table 3, which summarises the categories used by a UK tertiary hospital. In the workbook please enter the differences between the reader’s system and the UK system to reflect on the advantages/disadvantages of both.
Likelihood score | Rare | Unlikely | Possible | Likely | Almost certain |
---|---|---|---|---|---|
Will probably never happen/recur | Unlikely to happen again/recur, but it may do so | Might happen or recur occasionally | Will probably happen/recur but it is not a pressing issue | Will surey happen/recur possibly frequently | |
Catastrophic | 5 | 10 | 15 | 20 | 25 |
Major | 4 | 8 | 12 | 16 | 20 |
Moderate | 3 | 6 | 9 | 12 | 15 |
Minor | 2 | 4 | 6 | 8 | 10 |
Negligible | 1 | 2 | 3 | 4 | 5 |
Incident likelihood and risk scoring (risk scoring = consequence x likelihood).
Low risk = 1-3; Moderate risk = 4-6, High risk = 8-12; Extreme risk = 15-25.
Summary of the reader’s local system Reflection on differences between the UK and the reader’s own system (if applicable) |
Identifying and classifying adverse events, analysing the relevant risks, determining the likelihood of recurrence and determining lessons at both individual and organisational level is pointless without communicating the result to the individuals involved and (while maintaining anonymity) with the entire team. If this step is missed, the opportunity to learn from error will be lost forever, not to mention that the incident will surely reoccur [9].
In the author’s experience, the UK is at the forefront of recognising, managing and learning from errors and incidents with a nearly two decade-long history in the NHS. The National Quality Committee issued a document in 2013 (Concordat 2013) promoting the culture of learning from errors, the importance of timely feedback and the culture of candour. While the concordat is mostly a manifesto, another national organisation, the National Reporting and Learning Service, developed a seven-step tool to help with the practical application of this relatively new concept into the day-to-day operation.
However, even the English system has minor flaws. NHS England does not have a uniform reporting system and procedure, rather, it is left to hospitals to choose the best method. Most Trusts have their own classification system, which may differ significantly from one another. Unfortunately, these differences can conceal system-wide problems, so many advocate the need in favour of a unified, national system. Inarguably, a single system, similar to aviation, would simplify detection, facilitate detection and management of adverse events, as well as provide all level healthcare staff with transferable skills that can be applied in practice and used anywhere in the country.
Using Table 4 as a guide the reader should review the example of a clinical error and mark their recommendation in the workbook. Once the exercise is complete please review their answers against the hospital investigator’s recommendations (Table 5) and reflect on the differences.
NRLS steps |
---|
Build a safety culture |
Lead and support your staff |
Integrate your risk management activity |
Promote reporting |
Involve and communicate with patients and the public |
Learn and share safety lessons |
Implement solutions to prevent harm |
Summary of the NRLS 7 steps.
Trust measures to mitigate errors |
---|
No patient can self-discharge with an alleged mental health issue. |
Patients with alleged mental health issues needs senior review prior discharge. |
CDU Lead to revise CDU review policies and Mental Health Referral pathway. |
Promote and appraise reporting. |
Duty of Candour applies, patient shall be called and a formal letter might be considered. |
Learning points to be discussed on nursing training day and junior teaching. |
Compulsory CDU checklist prior to (self) discharge. |
The investigators recommendation based on the above NRLS tool.
The reader’s recommendations Reflection on the differences |
In the final section of the chapter we will have a quick trouble-shooting run-through to identify the potential barriers. At the moment, in the Anglo-Saxon territories incident recognition is based on voluntary reporting hence can only be as effective as often it is used.
The first difficulty stems from the inherent weakness of any self-reporting voluntary system; any non-mandatory, non-punitive, but at the same time non-incentivising activity depends solely on the level of motivation of those carrying out the activity. Not surprisingly, the sensitivity of hospital incident reporting systems (i.e. how many events does the system detect at all) is around 30% [10], while its specificity (i.e. how the detection rate relates to actual errors) is even lower: 14% [11].
To explain the poor sensitivity and specificity, similar answers were found throughout the world, regardless of political setting, religion, culture, or even clinical setting, whether inpatient and outpatient care, hospital or GP practice. This similarity highlights the importance of the human factors in reporting. A USA primary care survey found [12] that the time spent writing a report was inversely proportional to the frequency of reporting. Iranian authors [13] found that hospital workers reported only half of serious medication errors. According to their results, fears of accusations, retaliation, and the reporting burden (“it takes too long to write”) were the main disincentives behind non-reporting. It was also clear from the responses that almost all practitioners stated in unison that “there is no need to report if there was no problem with the patient”. The barriers of reporting seem to be similar in Canada: according to a hospital study [14], the timing of the reports was proportionate with factors perceived important by the responders: incidents endangering patient or staff safety, while the time spent writing the report, or the user unfriendly reporting interface significantly slowed down reporting speed. According to the study, professional identity, lack of information, unclear organisational relationships, and fear of retaliation also proved to be important barriers. Another Iranian article [15] concluded that the main barriers to reporting were the lack of effective reporting systems, complicated forms and the lack of collegial support. They also concurred with other studies that incidents perceived as minor were less frequently reported. The study highlighted significant differences between genders and occupations: women tend to report earlier than men, and nursing staff are more likely to report in writing than doctors. Most studies emphasised that reporting success was also positively influenced by timely, useful feedback. This is probably a common human trait, and the lack of effective communication of results or recommendations can easily cool an individual’s enthusiasm, as no one likes to work unnecessarily.
In conclusion, the success of reporting is proportional to low reporting burden and the accessibility to information. Thus, when designing an ideal system, cognitive- (understanding the importance) and emotional factors (enthusiasm, fear, satisfaction, etc.) as well as technological, organisational, and cultural aspects must be taken in consideration to facilitate easy and efficient reporting.
By adopting the concept of learning from errors, medicine has taken the initial step to eliminate the “blame and shame” culture. However, there is still a long way ahead before openly admitting mistakes and capitalising on improvement potential of errors become the new norm. To build a new world, where the truth of “to err is human” is rediscovered, the full support of both mass and social media will also be needed. Presently, health-related news in the media can be frightening. Articles and interviews have never highlighted the fact that many important, forward moving changes in medicine were actually triggered by serious, even fatal errors. The attitude of the media and also the public opinion must be changed to acknowledge that it takes enormous courage and honour to openly admit mistakes instead of waiting out the consequences. Such moral strength may drive development in both individual and organisation level. Only such new, non-punitive but supportive systems are likely to be able to overcome deep-rooted emotional barriers such as fear, anxiety, guilt and appraise compassionate performance.
The authors of the chapter are also convinced that medical and media professionals alone will surely not be able to create this new system: the patients must to be given more weight in planning and design of care systems, as ultimately, we are working with them, not for them. In this new structure, patients (and caregivers) are more likely to receive high level of partnership-based carewith practitioners standing a better chance that a one-off error may not be ruining an otherwise immaculate long service careers of dedicated, talented professionals who dedicate their time and knowledge to helping others [16, 17].
What systems are in place in your setting to report harm? How are Datix, RIDDOR and Patient Liaison reports are collated and reported to you and your team? How many entries did you make in the adverse event log during the last year? How many should you have reported?
Please ensure you are familiar with the risk assessment tools in your department? Are there any differences compared comparing to the above model? Is your tool better or worse than the tool above?
How are adverse events dealt with in your organisation? How are the learning points communicated to your team?
Are you aware of the effectiveness of root cause analysis within your organisation? If yes, what is the result?
How would you manage your team and in similar situation described in Box 2?
|
What are the most common strategies to communicate errors and consequent recommendations to the team in your organisation?
|
"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
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\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. 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