**3.5 Paneth cells**

Paneth cells are physiologically found at the distal small intestinal crypts of Lieberkühn and contain abundant secretory granules. Their unique histomorphological features implicate special functions in cellular homeostasis as well as in the establishment and configuration of the mucosal barrier as a physical and highly organized immune interface [43]. Previous studies suggesting the existence of Paneth cells in the chicken remained controversial. However, recent research has supported Paneth cells existence in the small intestine of the chicken by electron

microscopy confirming the presence of granulated secretory cells at the base of the crypts in the chicken small intestine. The researchers also confirmed by Western blot the expression of lysozyme protein, which is specifically secreted by the Paneth cells in the small intestine [44]. Paneth cells have the morphological characteristics of a professional secretory cells, including an extensive ER, a Golgi apparatus and an internal secretory granule. The first assumption that Paneth cells had a hostdefense function emerged when lysozyme was identified as a product of these cells [45]. After that, it was discovered that Paneth cells secrete antimicrobial peptides (AMP) or host defense peptides (HDPs) which are important host-defense substances in the communication between host and microbiome. One of the most well characterized are β-defensins [46]. In addition to defensins, Paneth cells is able to secrete other AMPs including secretory phospholipase A2, Reg III, angiogenin 4 and cathelicidins [47–49].

#### **3.6 Host defense peptides**

HDPs are generally positively charged small peptides with amphipathic properties [50]. These peptides present in the GIT display an important, but often overlooked role in the first line of defense. With the first avian HDPs identified in 1990s [51], the information about avian HDPs has increased considerably in the subsequent decades. Currently, avian β-defensins and cathelicidins are the two major classes identified and extensively studied in chickens [52, 53].

HDPs were initially called antimicrobial peptides (AMPs), because they are characterized by the direct antimicrobial activities against a broad spectrum of numerous pathogens, including gram negative and positive bacteria, fungi, and even certain viruses [54–56]. Generally, the cytoplasmic membrane of pathogenic organisms is a frequent target for HDPs. The amphipathicity and cationic charge of HDPs allow the initial contact with membrane electrostatically, as most bacterial surfaces are hydrophobic and anionic. The peptides then insert into phospholipid bilayers and induce pore formation in membranes by toroidal pore formation, carpet formation and barrel-stave formation, resulting the cytoplasmic leakage and death of pathogens [54, 57–59]. Besides pore formation in membranes, some HDPs can directly penetrate into cells and interfere with intracellular molecules, interrupting cell wall formation, DNA and RNA synthesis, protein translation and post-translational modification [57, 60].

To be specific, chicken AvBD1, −2, and − 7 exhibit high efficiency against a large variety of both gram-negative (*E. coli*, S. enteritidis, S. typhimurium, C. jejuni, and *K. pneumoniae*) and gram-positive (*S. aureus*, B cereus, *L. monocytogenes*, S. haemolyticus, and S. saprophytus) bacteria [51, 61–64]. AvBD1 and − 7 also efficiently kill P. aeroginosa and E. cloaca, while AvDB2 showed reduced efficacy [61, 64]. AvBD4, −5, and − 11 protect host from invasion of S. enteritidis and S. typhimurium, however their antimicrobial activities on other bacteria species remain to be determined [63, 65, 66]. Although AvDB8, −9 and − 13 are active against *E. coli*, respectively, they exhibit a minimal activity against several other bacteria [66–69]. Based on studies of different AvBD isoforms, it seems that both structure and catholicity are important for antimicrobial activity but disparity in the preference of gram-negative or positive bacteria.

All four chicken CATHs show antimicrobial capacities in the same order of magnitude against a wide range of gram-negative and positive bacteria, and fungi [70–73]. Similar to AvBDs, the structure and cationic charge are equally important for their antimicrobial activities. The presence of an alpha-helical region in N-terminal and hinge region around the center of the peptide are important for antimicrobial. Removal of N-terminal alpha-helix in CATH2 truncation or

**125**

*Secretory Defense Response in the Bird's Gastro-Intestinal Tract and Nutritional Strategies…*

disrupted helix formation in a-helical synthetic peptide leads to the loss of antimicrobial activity [72, 74, 75]. Although deletion of C-terminal alpha-helix in CATH2 reduces the activity against pathogens, the remaining truncation is still capable to kill bacteria [75]. The truncation of CATH2 with N-terminal alpha-helix alone shows increased antibacterial activity [76]. The hinge region plays a key role in the insertion of CATH into the bacterial membrane and pore formation [74, 77]. Disruption of the hinge region by point mutation or removal in the center of the CATHs largely decreases the antimicrobial activity [72, 74, 78]. The cationicity of CATH and AvBDs is important for the initial contact with the surface of bacteria. The higher cationic charge in CATH2 and the synthetic analogs results in the better

In addition to direct antimicrobial activity, the HDPs exhibit the immunomodulatory function, involving inflammation and chemotaxis. Chicken AvBD13 was reported as a direct TLR4 ligand [79], increases production of IFN-γ and IL-12 in mouse monocytes through activation of TLR4-NFκB axis. Combined with the evidence that AvBD13 increases serum IgG and IgM levels in chicken and induces lymphocytes proliferation in spleen after the administration of the infectious bursal disease vaccine (IBDV) [80], activation of TLR signaling by AvBD13 indicates an immune enhancement rather than a merely pro-inflammatory effect. Moreover, chicken AvBD1 fusion protein expressed by IBDV enhances CD4+, CD8+, and CD3+ T-cell proliferation, increases antibody titers, improves survival rate in in vivo experiment [81]. Additionally, HDPs have been shown chemotactic effect. Investigations about immunomodulation by avian AvBDs and CATHs are mainly limited to NF-κB activation, cytokine production, and direct immune activation. The similar findings in human and mouse studies suggest the conserved function of HDPs among species, providing the guideline for the application and future

Unlike the innate immune system which attacks only general threats, adaptative mucosal immune system is triggered by exposure of potentially dangerous pathogens. However, sometimes if overlaps some of their functions. The three most key roles of that system are: the induction of an efficient and appropriate immune response to pathogenic invaders, the tolerance of the commensal microorganisms of the intestine as well as the induction of the tolerance of nutrients and other environmental immunogens. Responses of the systemic immune system can originate from or be modified by the mucosa; this is exemplified by the attenuation of systemic immune responses to a protein that has first been fed orally to the animal (oral tolerance). Thus, the mucosal immune system must maintain the delicate balance between responsiveness to pathogens and tolerance to a vast array of other harmless antigens encountered at mucosal sites. This balance is achieved through the interplay of innate and adaptive (B- and T-lymphocyte) mechanisms [82]. The adaptative immune system in the GIT has features that are distinct from adaptative immune systems in other organs. The major form of adaptative immunity in the gut is humoral immunity directed at microbes in the lumen. This function is mediated mostly by dimeric IgA antibodies that are secreted into the lumen of the gut. Cellular adaptative immunity is carried out by an intraepithelial lymphocytes (IEL) in healthy adult bird includes major subsets of NK and T cells bearing the γδ or αβ form of the T cell receptor (TCR). In contrast to other tissues, B cells are almost entirely absent from the IEL and the T cells predominantly express the CD8 coreceptor with smaller populations of TCRαβ+ CD4+ and CD4 + CD8+ cells [83, 84].

*DOI: http://dx.doi.org/10.5772/intechopen.95952*

antimicrobial outcomes [72, 75].

research in poultry area.

**4. Adaptative immunity of the GIT**

*Secretory Defense Response in the Bird's Gastro-Intestinal Tract and Nutritional Strategies… DOI: http://dx.doi.org/10.5772/intechopen.95952*

disrupted helix formation in a-helical synthetic peptide leads to the loss of antimicrobial activity [72, 74, 75]. Although deletion of C-terminal alpha-helix in CATH2 reduces the activity against pathogens, the remaining truncation is still capable to kill bacteria [75]. The truncation of CATH2 with N-terminal alpha-helix alone shows increased antibacterial activity [76]. The hinge region plays a key role in the insertion of CATH into the bacterial membrane and pore formation [74, 77]. Disruption of the hinge region by point mutation or removal in the center of the CATHs largely decreases the antimicrobial activity [72, 74, 78]. The cationicity of CATH and AvBDs is important for the initial contact with the surface of bacteria. The higher cationic charge in CATH2 and the synthetic analogs results in the better antimicrobial outcomes [72, 75].

In addition to direct antimicrobial activity, the HDPs exhibit the immunomodulatory function, involving inflammation and chemotaxis. Chicken AvBD13 was reported as a direct TLR4 ligand [79], increases production of IFN-γ and IL-12 in mouse monocytes through activation of TLR4-NFκB axis. Combined with the evidence that AvBD13 increases serum IgG and IgM levels in chicken and induces lymphocytes proliferation in spleen after the administration of the infectious bursal disease vaccine (IBDV) [80], activation of TLR signaling by AvBD13 indicates an immune enhancement rather than a merely pro-inflammatory effect. Moreover, chicken AvBD1 fusion protein expressed by IBDV enhances CD4+, CD8+, and CD3+ T-cell proliferation, increases antibody titers, improves survival rate in in vivo experiment [81]. Additionally, HDPs have been shown chemotactic effect. Investigations about immunomodulation by avian AvBDs and CATHs are mainly limited to NF-κB activation, cytokine production, and direct immune activation. The similar findings in human and mouse studies suggest the conserved function of HDPs among species, providing the guideline for the application and future research in poultry area.


**1. Introduction**

Dental implant service is a life-changing treatment modality for many patients. Giving our patients a fixed restoration is a very rewarding procedure, especially if the patients have difficulties: gage reflex, bulky prostheses, lack in retention, stability, or support. Unfortunately, this is not applicable for all patients, especially patients who cannot afford multiple implants or bone grafting. By considering the strategic implants under the existing removable partial denture (RPD), we make implant treatment simple and affordable for more patients.

The removable partial denture (RPD) is the dental prostheses that the patient, who suffers the absence of some but not all the natural teeth, can readily insert and remove from his/her mouth. The prostheses restore the missing teeth as well as the gingiva and the missing bone if needed. Removable partial dentures (RPDs) are indicated for patients with a long edentulous span, too long for a fixed prosthesis. The RPD is indicated for a patient with no posterior abutment to support a fixed prosthesis, and the cantilever bridge is contraindicated. Also, it is preferred if excessive alveolar bone loss is encountered, especially in the esthetic zone. Those patients who are not indicated for bone grafting or unable to afford the costly treatment are good candidates for the removable denture (RD). The acrylic flang is a good approach to compensate for the bone and soft tissue deficiency within a short fabrication time and a less aggressive approach. Moreover, this treatment option allows the patient to remove his prostheses for easier intraoral access, subsequently, better oral hygiene. The RD enables the dentist to repair or adjust the prostheses easily.

On the other hand, RD is less secure with limited retention and stability than fixed prostheses. RD metal clasp may compromise the final esthetic result. It may act as a gum stripper and accelerate alveolar bone resorption. These drawbacks in the RD can be managed by upgrading the RD using strategic implants, which are "the implants that change the prosthetic support type to a more favorable configuration" [1].

In this chapter the folllowing points is going to be discussed:

	- Kennedy classification system
	- Steffel classification and modified Steffel classification
	- Implant-Corrected Kennedy (ICK) Classification System for Partially Edentulous Arches
	- Strategic mini dental implants (MDI) and standard dental implant (SDI) under existing RPD, how many implant?
	- The abutment prosthetic value


**3. Type of polymorphisms**

The human genome comprises 6 billion nucleotides of DNA packaged into two sets of 23 chromosomes, one set inherited from each parent. The probability of polymorphic DNA in humans is great due to the relatively large size of human genome. Genomic variability includes a wide range of variations from single base pair change, many base pairs, and

Single nucleotide polymorphisms are the most common type of genetic variations in humans [3], due to their abundance across the human genome; single nucleotide polymorphisms (SNPs) have become important genetic markers for mapping human diseases, population genetics, and evolutionary studies. SNPs have become very important since technologies for DNA sequencing have become feasible and widely available. Advance continues at a rapid

A major step forward in genome identification is the discovery of about 30–90% of the genome which is constituted by regions of repetitive DNA which are highly polymorphic in nature [5]. Polymorphic tandem repeated sequences have emerged as important genetic markers and initially, variable number tandem repeats (VNTRs) were used in DNA fingerprinting. In recent years, evidence has been accumulated for the involvement of VNTR repeats in a wide

Throughout the past years, scientists have believed that genes strictly came in two copies in a genome. However, with the recent advancement in molecular technology, discoveries have revealed substantial segments of DNA, ranging in size from thousands to millions of DNA bases that could vary in copy number. Such copy number variations (or CNVs) encompass gene copies, newly discovered CNVs are important sources of genomic diversity [7, 8].

The development and use of DNA-based molecular markers is one of the most significant developments in the field of molecular genetics that facilitate the study of genetic variations

This chapter reviews the DNA-based genetic markers and their application in medicine, with a particular emphasis on common DNA-based genetic markers, including single nucleotide

Genomic variability at DNA level can be present in many forms including: single nucleotide polymorphisms, variable number of tandem repeats (e.g., mini- and microsatellites), transposable elements (e.g., Alu repeats), structural alterations, and copy number variations. It can occur in the nucleus or mitochondria. Two major sources: (1) mutations that may result as chance processes or have been induced by external agents such as radiation and (2) recombination. Once formed, it can be inherited, allowing its inheritance to be tracked from parent

The genomes of humans may be divided into different parts based on known functional properties; the coding and noncoding regions mostly do not code for protein [2, 9]. The coding

repeated sequences [2].

26 Genetic Diversity and Disease Susceptibility

spectrum of pathological states [6].

in health and diseases [5].

to child [3].

polymorphisms and short tandem repeats (STRs).

**2. Polymorphisms at DNA level**

rate [4].

#### **3.1. Single nucleotide polymorphisms**

Single base change is "high-density natural sequence variations in human genome" [14]. SNPs are mostly formed when errors occur (substitution, insertion and deletion). SNPs are prominent sources of variation in human genome and serve as excellent genetic markers. Some regions of the genome are richer in SNPs than others. SNPs may occur within gene sequences or in intergenic sequences. SNPs mostly are located in noncoding regions of the genome and have mostly no direct known impact on the phenotype of an individual but their role till now remains elusive, and depending on where SNPs occurs, it might have different consequences at the phenotypic level [3].

#### **3.2. Insertion/deletion polymorphisms**

It is a type of DNA variation in which a specific nucleotide sequence of various lengths ranging from one to several 100 base pairs is inserted or deleted. Indels are widely spread across the genome. Some authors consider one base pair as SNPs or repeat insertion/deletion as indels.

#### **3.3. Polymorphic repetitive sequences**

DNA repeats can be classified as interspersed repeats or tandem repeats. This can comprise over two-thirds of the human genome [15]. Interspersed repeats are dispersed across the genome within gene sequences or intergenic and include retro (pseudo) genes and transposons. Tandem repeats or variable number tandem repeats (≥2 bp in length) that are adjacent to each [16] can involve as few as two copies or many thousands of copies. Centromeres and telomeres largely comprise tandem repeats. Despite increasing evidence on the functionality of DNA repeats, their biologic role is still elusive and under frequent debate [11]. Tandem repeats are organized in a head-to-tail orientation; based on the size of each repeat unit, satellite repeats can be further divided into macrosatellites, minisatellites, and microsatellites [17]. Some of these repeats are described as follows: macrosatellites, with sequence repeats longer than 100 bp, are the largest of the tandem DNA repeats, located on one or multiple chromosomes [11], minisatellites, stretches of DNA, are characterized by moderate length patterns, 10–100 bp usually less than 50 bp [9, 18], and microsatellites also known as short tandem repeats (STRs) repeat units of less than 10 bp, [3].

Single nucleotide polymorphisms within a coding sequence cause genetic diseases including sickle cell anemia. SNPs responsible for a disease can also occur in any genetic region that can *eventually* affect the expression activity of genes, for example, in promoter regions. SNPs in the noncoding region of the gene, though their effect is still debatable, most of the genome mostly consists of regulatory elements that control gene expression, but these regions have remained largely unexplored in clinical diagnostics due to the high cost of whole genome sequencing and interpretive challenges. Clinical diagnostic sequencing currently focuses on identifying causal mutations in the exome, where most disease-causing mutations are known

DNA Polymorphisms: DNA-Based Molecular Markers and Their Application in Medicine

http://dx.doi.org/ 10.5772/intechopen.79517

29

Another important group of SNPs is the one that alters the primary structure of a protein

However, some SNPs are not causative, some SNPs are in close association with, and therefore segregate with, a disease-causing sequence so, the presence of SNP correlates with the presence or an increased risk of developing the disease; these SNPs are useful in diagnostics,

Single nucleotide polymorphisms can be used as genetic markers for constructing high genetic maps and to carry out association studies related to diseases because of their abundance and the availability of high throughput analysis technologies. SNPs have become an important

There are numerous strategies that can be implemented to new single nucleotide variant (SNVs) discoveries; the most common and well-known method is by direct sequencing and in comparison to a puplic or other sequence date base [25, 26] or locus specific amplification of target genomic region followed by sequence comparison [27, 28]; prescreening prior to sequence determination is needed. SNV detection encompasses two broad areas: (1) scanning DNA sequences for previously unknown polymorphisms and (2) screening (genotyping) individuals for known polymorphisms. Scanning for new SNVs can be further classified to two different types of approaches, the first one being the global (or random approach) and the other one being the regional (targeted approach) [14]. There are certain methods which have been developed for using SNVs randomly in the genome; "such as representation shotgun sequencing [14, 29], primer-ligation-mediated PCR [14, 30] and degenerate oligonucleotide–

Haplotypes are groups of SNPs that are generally inherited together. Haplotypes can have stronger correlations with diseases or other phenotypic effects compared with individual

Microsatellites are short tandem repeats (STRs), repeat units, or motifs of less than 10 bp; because of high variability, microsatellite loci are often used in forensics, population genetics, and genetic genealogy. Significant associations were demonstrated between microsatellite

SNPs and may therefore provide increased diagnostic accuracy in some cases [32].

involved in drug metabolism; these SNPs are targets for pharmacogenetics studies.

application in the development and research of genetic markers [14].

disease prediction, and other applications [3].

to occur.

primed PCR" [14, 31].

**4.2. Microsatellites (short tandem repeats)**

variants and many diseases [15].

#### **3.4. Structural and copy number variations**

Structural and copy number variations (CNVs) are another frequent source of genome variability [6, 19, 20]. The term CNVs therefore encompasses previously introduced terms such as large-scale copy number variants (LCVs) [19], copy number polymorphisms (CNPs) [20], and intermediate-sized variants (ISVs) [21]. Some currently used terms are structural variations; a genomic alteration (e.g., an inversion) that involves segments of DNA > 1 kb, copy number polymorphisms; a duplication or deletion event involving >1 kb of DNA [22], intermediatesized structural variant; and a structural variant that is ∼8–40 kb in size, this can refer to a CNVs or a balanced structural rearrangement (e.g., an inversion) [21].


**2.12 Elastic properties of coiled CNT reinforced Nano composite**

With the invention of Carbon nanotube with advanced material properties, various nano composites had been developed [14]. A new algorithmic representative volume element (RVE) and finite element method had been formulated to find the elastic properties of coiled Carbon NanoTubes (CCNT). The elastic properties had been explored with the respect to interphase, fiber volume fraction, orientation, number of coils, tube diameter, coil diameter and helix angle using FEM. The elastic moduli of the nanocomposites were found to decrease with increase in the number of coils. Also it had been found that SWNT offers better reinforcement when compared with CCNT reinforcement.


*4.2. Comparison with Previous Studies*

Previous reports related to EGFR inhibitors showed consistent findings with the current study. A recent meta-analysis of 90 retrospective or prospective cohort studies and clinical trials showed the comparable effect of gefitinib vs. erlotinib [20]. The RR (95% CI) for ORR and HR (95% CI) for PFS were 1.05 (1.00–1.11) and 1.00 (0.95–1.04), respectively [20]. Another network meta-analysis of 11 clinical trials also showed the similar PFS between gefitinib and erlotinib [21]. However, unlike our findings, the third-generation EGFR inhibitor osimertinib was found to have a longer PFS (HR 0.71, 95% CI 0.54–0.95), and the significant difference between the second-generation EGFR inhibitor afatinib and standard of care (either gefitinib or erlotinib) was not observed (HR 0.96, 95% CI, 0.86–1.17) [21].

In a large medical chart review of 1471 participants with ALK-positive NSCLC among a total of 27,375 recorded subjects from seven countries, crizotinib showed a significant improvement in complete response (odds ratio (OR) = 2.65, 95% CI = 1.69–4.15) and reduction of recurrence/progression (odds ratio = 0.38, 95% CI = 0.24–0.59) compared to controls [22]. Also, a recent network meta-analysis of ALK inhibitors showed consistent findings among treatments in both ORR and PFS outcomes [23]. In Fan et al.'s study, a remarkable improvement in ORR was shown: the ORs (95%CI) for crizotinib, ceritinib, and alextinib were 11.69 (4.29–36.56), 7.85 (3.44–19.27), and 6.04 (3.33–11.71), compared to chemotherapy, respectively [23]. The superior efficacy of alectinib in PFS might be associated with the resistance to crizotinib among ALK-positive NSCLC patients, which reduces therapeutic response to crizotinib [24,25]. Although ceritinib is also a second-generation ALK inhibitor, our study showed that there is no signicant difference in the efficacy between ceritinib and crizotinib. Similarly, the recent meta-analyses of pooled estimates reported that crizotinib might have higher ORR [66% (58–74%) vs. 52% (38–66%)] and longer PFS [9.27 months (8.28–10.26) vs. 5.92 months (4.36–7.48)] than ceritinib,

although no statistical test was performed [26]. It remains unclear why ceritinib did not show a superior efficacy unlike alectinib.


**2. Grouting mechanisms**

Hydrofracturing of soil occurs in many important geotechnical engineering issues. It corresponds to the process of initiation and propagation of a crack by injecting water and air as well as chemicals into soils. As the pressure of the fluid injected surpasses a certain threshold value, the hydrofracturing of soil is thus triggered. A typical application of hydrofracturing is fracturing grouting. The fracturing grouting that involves the intentional hydrofracturing of soil with a low viscosity grout to generate a network of interconnected grout lenses has been extensively used to create surface heave and compensate settlements as well as strengthen the soil. To implement an effective field application of the fracturing grouting, a good understanding of its fundamental mechanism is deemed to be necessary. Wong Ron and Alfaro Marolo carried out a field mapping of sand-propped hydraulic fractures at a contamination remedial site where the ground is primarily consisted of silt and clay. The fractures were found to be nearly horizontal, indicating that the ground is overconsolidated, with a K0 value greater than unity [31]. The sand proppant was thicker at locations where soils were relatively weak, but there was no strong evidence that soil stratigraphy at this worksite controlled the orientation of the fractures. Murdoch and Slack reported similar results in sand-propped hydraulic fractures [32]. Additionally, the horizontal fractures imply that the shallow soil strata should be overconsolidated. Moreover, the elevated volume would be considerably smaller than the injected volume in the event the hydraulic fractures vented to the ground surface. Liu and Yuan established an in situ slurry fracturing apparatus to analyse the slurry fracturing and fracture propagation phenomena [33]. It was observed that the fracturing pressure was highly related to the soil and slurry properties and that slurry with large bulk density and high viscosity was beneficial in preventing slurry fracture propagation. Conducting grouting in clay due to its low permeability rules out any other grouting techniques other than fracturing grouting. The excess porewater pressure generated during grout injection is greater than the in situ effective stress, leading to fractures in the surrounding clay. Existence of fractures accelerates the consolidation process and shortens the strength increase time due to consolidation. During injection, the fractures provide a channel for exchangeable cations, which make the strength increase due to chemical reactions much more quickly than anticipated. Additionally, the compensation efficiency may not be governed by clay type but by the setting time of grout, soil stress history, injection volume of grout and so on. However, the high mobility and low viscosity of the grout can lead to an inability of limiting the travel of grout, thereby resulting in a lower soil-heaved volume to injected volume of grout ratio also known as the grouting efficiency. The grouting efficiency is generally smaller than 1 due to the loss of fluid, resulting from the bleeding effect of grout and escape of the grout from the designated area by migration along fractures, and the ground settlement caused by the dissipation of excess porewater pressure generated in injection [31]. Marchi et al. carried out a comprehensive case study in Venice where a rather unique soil fracturing intervention was implemented to improve the mechanical properties of the soft silty clay underlying the ancient Frari bell tower [34]. For soils with negative values of liquidity index, the gradients from the plots of fracturing pressure against initial confining pressure are approximately 2, which indicated the fracture initiated by tensile failure in these cases, while for soils with positive values of liquidity index, the gradients are approximately 1, indicating that the fracture was triggered by shear failure. Komiya et al. conducted a field trial of shield tunnelling in a deep soft clay deposit to investigate the long-term consolidation effect on grouting efficiency [25]. The grouting programme was consisted of the tail void grouting and grout jacking. In both cases, the monitoring results indicate that the upward displacement owing to grout injection was negated by the consolidation settlement resulting in a net settlement. The considerable consolidation of clay after grout injection due to the dissipation of the excess porewater pressure generated as the grout intruded the sensitive and compressible clay contributed to this phenomenon. This also indicates that the grouting efficiency in soft clay may be negative.

grouting programme. The differential settlement or tilting of building, for instance, can be contributed not only by the soil right below the building foundation but by the successive soils. Thus, a grouting programme aimed to first stabilise the successive soils by 'stabilisation' grouting and then to lift the tilted building by 'jacking-up' grouting in the foundation soil is proved to be effective [24]. In the event that the grouting programme is designed to improve the properties of the foundation soil only, the jacking of the tilted building would not be effectively implemented due to a lack of the sufficient reaction forces given by the successive soils. Additionally, the intrusion of grouts may swell the cohesive soil and generate the positive excess porewater pressure. As long as the porewater pressure dissipates along with time, the associated settlement could override the heave generated during grout intrusion and thus result in a negative final compensation efficiency which is defined as a ratio of the total heaved volume to the injected volume of grouts [25–29]. Since the fracturing grouting due to easy travelling of the low viscosity grouts could generate higher porewater pressure than compaction grouting, regrouting at the same injection point is deemed to be necessary in order to change the stress state of cohesive soil to the overconsolidated state from its ordinary state [24, 30]. Any further grouting activity would only generate negative excess porewater pressure, and resettlement would not be occurred, thereby improving the final compensation efficiency. If both closer spacing between grout injection points and simultaneous injection are introduced, the final compensation efficiency can be further improved [27]. The above indicates that configuration and design parameters of the grouting programme play a leading

104 Current Topics in the Utilization of Clay in Industrial and Medical Applications

The objectives of this study are (i) to present the results of an application of this proposed simultaneous and multiple grouting technique for levelling two tilted buildings seated on soft soil deposits in Taipei basin, (ii) to verify the effectiveness of introducing a grouting programme consisting of the stabilisation grouting of first stage and jacking-up grouting of the second stage by analysing the elevated and settled efficiencies and (iii) to outline the lessons

Hydrofracturing of soil occurs in many important geotechnical engineering issues. It corresponds to the process of initiation and propagation of a crack by injecting water and air as well as chemicals into soils. As the pressure of the fluid injected surpasses a certain threshold value, the hydrofracturing of soil is thus triggered. A typical application of hydrofracturing is fracturing grouting. The fracturing grouting that involves the intentional hydrofracturing of soil with a low viscosity grout to generate a network of interconnected grout lenses has been extensively used to create surface heave and compensate settlements as well as strengthen the soil. To implement an effective field application of the fracturing grouting, a good understanding of its fundamental mechanism is deemed to be necessary. Wong Ron and Alfaro Marolo carried out a field mapping of sand-propped hydraulic fractures at a contamination remedial site where the ground is primarily consisted of silt and clay. The fractures

role in the success of project.

learnt from the case studies.

**2. Grouting mechanisms**

It is reported by Au et al. that for normally consolidated or slightly overconsolidated clays, the significant decrease in the grouting efficiency with time was due to the dissipation of the positive excess porewater pressure generated during grout injection [26]. However, for heavily overconsolidated clays, the excess porewater pressure was positive at the injection boundary, but it was negative at the outer boundary due to dilative behaviour of the clay. The compression around the injection point induced by the dissipation of the positive excess porewater pressure and swelling some distance away from the injection point caused by the dissipation of the negative excess porewater pressure led to a negligible consolidation effect. As discussed, the bleeding effect of grout has been deemed to be one of the factors affecting the grouting efficiency. Au et al. conducted additional injection tests with grouts that were prepared with the water-to-cement (w/c) ratios of 0.5, 1 and 3, respectively, using the 50-mm diameter oedometer [26]. The final grouting efficiency was reduced from about 20% for the grout with the w/c ratio of 0.5 to around −30% for the grout with the w/c ratio of 3. The higher the solid content of grout, the lesser the bleeding effect of grout, and the higher the final grouting efficiency. The effect of boundary condition was also examined by injecting 5 ml of grout into the modified oedometers with the diameters of 50 mm and 100 mm, respectively [26]. The results show that the reduction in the radial boundary size enabled the final grouting efficiency to be improved dramatically as the overconsolidation ratio was within a range of 1–2. In other words, the smaller the spacing of injection point, the smaller the magnitude and extent of excess porewater pressure, and the higher the final grouting efficiency. It is common practice to introduce the tube-a-manchette (TAM) while performing compensation grouting, which allows grout to be injected many times from the same injection port. In the case that a given volume of grout is injected over a fixed area, it is possible to either regrout many times at the same port with smaller injection volumes or, conversely, conduct a small number of regrouting but with larger injection volumes. A series of injection tests comprising the regrouting injection and single injection tests were undertaken in normally consolidated clay specimens to investigate the effect of waiting period on the long-term grouting efficiency after injection [26]. An injection of 5 ml for each injection was made four times for the regrouting injection tests. The test results were compared with the result of a single injection test which was undertaken by injecting 20 ml at once. The results show that in the stage of consolidation, more excess porewater pressure was generated in the subsequent injections for the regrouting injection test, thereby leading to a lower grouting efficiency than that from the single injection test. Additionally, the efficiency of compensation grouting defined as the ratio of building settled volume to total injected volume of grout may be further reduced as only the grout beneath the mat foundation can contribute to the effective lift of titled building. Moreover, injection of extra quick setting grout can only be achieved by introducing the two-shot grout hose system [35]. The shorter the grout gel time, the lesser the excess porewater pressure generated, and the higher the final compensation efficiency. To summarise, it is evident that there are many factors (soil stress state, boundary condition, bleeding of grout, regrouting, grout rheological characteristics, grout hose system and so on) affecting the final compensation efficiency. Lifting tilted building in soft clay deposit can be better achieved by introducing a grouting programme that at least takes the previously discussed factors into account. Also, the two-stage grouting consisting of the stabilisation grouting of first-stage and jacking-up grouting of second stage may be used to ensuring the final compensation efficiency.

**3. Case descriptions**

**3.1. Engineering geology**

**3.2. Grouting programme**

Based upon the preliminary geological investigation [36], the ground for Case A is generally consisted of a 1.5-m-thick surface backfill, a 4.5-m-thick low plasticity clay, a 4-m-thick silty sand and a successive very soft silty clay, as shown in **Figure 1**. The blow count N value for the clays varies from 1 to 4, whereas for the sands it varies from 5 to 10. The groundwater level is close to the ground surface. The soft soil deposits can thus easily get softened once

Clay Grouting Mechanisms and Applications http://dx.doi.org/10.5772/intechopen.74091 107

The geological profile at the worksite of Case B is consisted of a 4-m-thick alluvial loam, a 7-m-thick very soft silty clay and an underlying soft silty clay, as shown in **Figure 2**. The static groundwater level in the vicinity of the worksite is some 2 m below the surface. The N value varies from 1 to 2 for the very soft silty clay, whereas for the soft silty clay, it varies from 2 to 3. The soft clays thus can behave as a fluid once subjected to construction disturbances.

In the Case A, the eight-storey reinforced concrete building with one-storey basement was seated on the silty sand. The nonuniform consolidation of the successive silty clay led to the tilting of the eight-storey building afterwards. Since the tilting of the eight-storey building was amplified along with time, jacking the tilted eight-storey building back to the acceptable range of tilting was urgently needed. After considering all the possible alternatives to level up the tilted eight-storey building, grouting method was chosen due to the two reasons, that

disturbed or even washed away as subjected to significant hydraulic gradients.

**Figure 1.** Geological profile of worksite and properties of soft soil deposits (Case A).


**2.2 Structure of classical arsenomolybdates**

Up to now, various structures of arsenomolybdates were reported and discussed in detail. The following types are classical arsenomolybdates clusters: (i) {As2Mo6} type, Pope's group reported the first {As2Mo6} cluster [28], in which the Mo6O6 ring is constructed from six MoO6 octahedra connected via an edge-sharing mode, the opposing faces have two capped AsO4 tetrahedra. Then Zubieta's group and Ma's group reported [MoxOyRAsO3] n� (RAsO3 = organoarsenic acid) and [Mo6O18(O3AsPh)2] 4�(Ph = PhAsO3H2) clusters [29, 30]. (ii) {As6Mo6} type, which is derived from the A-type Anderson anion [(MO6)Mo6O18] 10�, the central {MO6} octahedron is coordinated with six {MoO6} octahedra hexagonally arranged by sharing their edges in a plane. The cyclic As3O6 trimers are capped on opposite faces of Anderson-type anion plane. Each As3O6 group consists of three AsO3 pyramids linked in a triangular arrangement by sharing corners and bonded to the central MO6 octahedron and two MoO6 octahedra via μ3-oxo groups. Wang and co-workers reported the compound (C5H5NH)2(H3O)2[(CuO6)Mo6O18(As3O3)2] [31], Zhao groups synthesized the compound [Cu(arg)2]2[(CuO6)Mo6O18(As3O3)2]�4H2O [32]. (iii) {AsMo12} type, has a AsO4 tetrahedron at the center and 12 surrounding MoO6 octahedra, such as [NBu4]6[Fe(C5H5)2][HAsMo12O40]2 [33]. {As2Mo9}) type, is derived from the trivacant Keggin moiety, which is capped by a triangular pyramidal {AsO3} group, e.g., [Cu(en)2H2O]2{[Cu(en)2][Cu(en)2AsIIIAsVMo9O34]} 2�4H2O and [Cu(en)2 (H2O)]4[Cu(en)2(H2O)2]{[Cu(phen)(en)] [AsIIIAsVMoVI 9O34]2} [34, 35]. (iv) {As2Mo18} type, as a classical Wells–Dawson cluster, can be described as two [AsMo9O34] 9� units derived from an Keggin anion by the removal of a set of three corner-sharing MoO6 octahedra, e.g., [Himi]6[As2Mo18O62]�11H2O [36].

In comparison with the classical arsenomolybdates, many nonclassical arsenomolybdates have also been prepared in the past of years, such as Ag12.4Na1.6Mo18As4O71 [37], (NH4)11[AgAs2Mo15O54]3�6H2O�2CH3CN [38], [AsIII 2FeIII 5MMo22O85 (H2O)]n� (M = Fe3+, n = 14; M = Ni2+ and Mn2+, n = 15) [39], {Cu(2,20 -bpy)}2{H2As2Mo2O14} [40], [{Cu(imi)2}3As3Mo3O15]�H2O [41], and so on. The novel arsenomolybdate structure is gaining more and more attention.

high-efficient proton delivery, fast multi-electron transfer, strong solid acidity and

photocatalytic activities. In particular, the integration of metal-organic frameworks (MOFs) into arsenomolybdates for photocatalysis has attracted widespread attention over the past decade, since MOFs combine porous structural and ultrahigh

Arsenomolybdates crystals reported were almost synthesized via self-assembly processes using hydrothermal method (**Figure 2**). Many factors in the synthetic process should be considered, such as reaction time and temperature, concentration of staring materials, compactness, pH values, and so on. The some experiments indicate that the temperatures are in the range of 110–180°C for srsenomolybdates synthesized, when the pH value of the mixture is adjusted to approximately 3–6.8,

(6 x) (abbreviated {As2Mo6}), [(MO6)(As3O3)2Mo6O18]

were easy to formed, when the pH value is within the range of 2.5–5.5 and 2–4,

{As2Mo18}) types were successfully synthesized. At the same time, the choice of transition metal, organic ligand, and molybdenic source have also affect for

3 (abbreviated {AsMo12}) and [As2Mo18O62]

4

6 (abbreviated {As2Mo9}) types

6 (abbreviated

excellent reversible redox activity [27], which may result to prominent

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

Based on these results, we provide a summary of recent works in the synthesis, structure, the photocatalytic activity, reaction kinetics and mechanism mechanisms of arsenomolybdates, which aim at finding the direction followed with the opportunities and challenges for the arsenomolybdates photocatalysis to accelerate the step to realize its practical application in degradation of

**2. Syntheses and structure of arsenomolybdates**

**2.1 Syntheses of arsenomolybdates**

*The potential application field of arsenomolybdates.*

(abbreviated {As6Mo6}) and [AsIIIAsVMo9O34]

internal surface areas.

organic dyes.

**Figure 1.**

[HxAs2Mo6O26]

[AsMo12O40]

**118**


**DNA-Binding Radioprotectors**

Pavel Lobachevsky1, Alesia Ivashkevich1, Olga A. Martin1,2 and Roger F. Martin1 *1Laboratory of Molecular Radiation Biology, Peter MacCallum Cancer Centre 2Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute 1Australia 2USA*


**2.4. Statistical analysis**

Statistical analysis using Student's t-test (SPSS, Version 11.0) was performed to find significant difference on lactobacilli count between LAMVAB and MRS 4.2. Pearson's correlation coefficient was used to investigate the correlation of lactobacilli count between LAMVAB and MRS 4.2 (SPSS Inc., Version 11.0, Chicago, USA). A significance level of p<0.05 was used.


**2. Materials and Methods**

The animal experiments were conducted in accordance with the corresponding German regulations and approved by the Ethics Committee of Lower Saxony for Care and Use of Laboratory Animals (LAVES) (Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit; reference: 33.12-42502-04-15/2044).

#### *2.1. Design of Experiments*

A total of 720 female one-day-old turkeys (B.U.T. Big 6) were obtained from a commercial hatchery (Heidemark GmbH, Ahlhorn, Germany). A total of three independent experiments (T1–T3) were carried out. For each of these experiments, 240 birds were used.

Before starting the experiments in the second week after hatch, the birds were housed in dry and clean floor pens in a quarantine stable. Flooring was covered with wood shavings (GOLDSPAN®, Goldspan GmbH and Co. KG, Goldenstedt, Germany). A commercially prepared pelleted diet was offered ad libitum (Best 3 Geflügelernährung GmbH, Twistringen, Germany).

Each experiment was started after the above described one-week adaptation period. For these experiments, specially manufactured boxes were used, twelve experimental pens (1.20 × 0.80 m) in total. Different flooring designs were used to establish different degrees of contact intensity of the animals to the manure (Figure 1).

**Figure 1.** Flooring designs used in the study: **G1** = entire floor pen with litter; **G2** = identical to G1 and additionally having floor heating (in red); **G3** = plastic covered steel slats in 50% of the pen (in blue) as well as an area with litter; **G4** = fully-slatted flooring with plastic covered steel slats and a sand bath (900 cm2). SB = sand bath,R=rope.

The first group served as a control. Animals were kept on dry wood shavings (G1—entire floor pen covered with litter). The second group was identically kept. The exception was an electrical floor heating system (Sauerland GmbH, Paderborn-Elsen, Germany) with an adjuster to control the temperature (G2—floor pen with litter with floor heating). Animals in these two groups continuously had full contact with manure. The pens in the third group (G3) were divided into two equal parts consisting of 50% solid flooring with wood shavings on the right-hand side and 50% plastic slatted flooring on the left-hand side. In the last group (G4), plastic slatted flooring with a sand bath (900 cm2) was used, the bath being disinfected and the sand replaced on a daily basis. Animals in G4 had no contact with litter except possibly in the sand bath. Plastic covered steel slats consisted of holes (15 × 10 mm) and bridges (plastic covered steel; 3.5 mm wide; Big Dutchman International GmbH, Vechta, Germany). The excreta were stored under the slatted floor at a depth of approximately 30 cm without any material being removed during the trial, besides small amounts of material needed for the samples as described below.

The boxes were placed in a randomized sequence in blocks of four subgroups (G1–G4) in the same stable, as previously described [25]. Two boxes of each block were placed on the right-hand side and two on the left-hand side of a central corridor (~1.70 m width). Airing was provided by vacuum air ventilation. This system was installed in the ceiling in two rows above the pens. Wood shavings were used as bedding material (1 kg/m2). Stocking densities reached a maximum of 25 kg/m2. Hanging type feeders were used (Klaus Gritsteinwerk GmbH & Co. KG, Bünde, Germany) as well as bell drinkers (Ferdinand Stükerjürgen GmbH & Co. KG, Rietberg-Varensell, Germany).

Before commencing with the trials one week after hatch, stables and all materials had been disinfected. Also, tests had been performed to exclude the occurrence of Enterobacteriaceae. All birds were allocated to four groups, each with three identical subgroups (n = 20 birds). Rearing was done until day 36. The birds had unlimited access to fresh water and feed (commercial pelleted growing diet). The environmental temperature was gradually reduced from about 33 ◦C for the one-day-old birds to about 20 ◦C by day 36. Lights were continuously on between days 1 and 3 and the photoperiod from day 4 onwards amounted to 16 h of light and 8 h of darkness.

In T1 there was no antibiotic treatment. This experiment served as a nontreated control trial. In contrast, animals in T2 were medicated with Baytril® 10% in drinking water (10 mg enrofloxacin/kg body weight per day—corresponding to an addition of 0.5 mL Baytril® 10%/L of drinking water, in accordance with the recommended dosage; Bayer Vital GmbH, Leverkusen, Germany). In the last trial (T3), the birds were not treated with any antibiotic in drinking water. Spillage of drinking water containing enrofloxacin was simulated. The amount of water losses was calculated according to experience from former trials, comparing water intake in turkeys using drinking bowls and nipple drinkers (data not shown). Water containing enrofloxacin (dosage: 0.5 mL/L of Baytril® 10%, amount 240 mL per day) was sprayed into the litter or on the slatted flooring only in the feeding area. Both, in T2 and T3, five-day treatments were performed at days 10–14 and days 26–30.

At the end of day 21, eight out of 20 birds in each subgroup were dissected. Final dissection for all remaining turkeys (n = 12/box) was done at day 36. The stunning method (percussive blow to the head) was conducted in accordance with Annex I of the Council Regulation (EC) No. 1099/2009, Chapter I, Methods, Table 1—Mechanical Methods [26].

#### *2.2. Collection of Cloacal Swabs and Manure Samples*

Samples (864 in total) were taken before treatment, directly after antibiotic treatment and at the end of the trial. Cloacal swabs were collected at day 2 and manure samples at day 9 before treatment (BT: before treatment stage). After the enrofloxacin treatment (AT), at day 15, manure samples were taken and six days later, cloacal swabs were taken (day 21). Final sampling (ET) was done for both (manure and cloacal swabs) at day 35. Cloacal swabs were always collected from 24 animals per group, i.e., in total, 96 randomly selected animals. Six samples from each type of flooring design (two samples per pen), in total 24 samples of manure, were taken from two defined locations (feeding area and resting area) in every pen for all trial stages (BT, AT, and ET). Manure samples were taken with a plastic cup (6 cm in diameter) which removed the whole litter material at these locations right down to the floor. All samples were immediately transferred to the laboratory for following analyses.


**7. Treatment of burns**

were more common; these patients were more likely to require skin grafting and treatment in the intensive care unit [12]. Moreover the abused/neglected children were more likely to come

The appropriate first aid after burn injury is very important in reduction of burn depth, which means that it influences the requirement for surgical treatment, can shorten the hospitaliza-

According to WHO, the person who gives the first aid to the burned child should stop the burning process by removing clothing and irrigating the burns; extinguishing flames by allowing the patient to roll on the ground, or by applying a blanket, or by using water or other fire-extinguishing liquids; use cool running water to reduce the temperature of the burn; in chemical burns, remove or dilute the chemical agent by irrigating with large volumes of water; and wrap the patient in a clean cloth or sheet and transport to the nearest appropri-

WHO also pays attention on the actions that the person who gives the first aid to the burned child should not do; for example, do not start first aid before ensuring your own safety (switch off electrical current, wear gloves for chemicals, etc.); do not apply paste, oil, haldi (turmeric), or raw cotton to the burn; do not apply ice because it deepens the injury; avoid prolonged cooling with water because it will lead to hypothermia; do not open blisters until topical antimicrobials can be applied, such as by a health-care provider; do not apply any material directly to the wound as it might become infected; and avoid application of topical medica-

The person who gives first aid to the child after the burn injury is usually the person that was present during the accident—in most of cases—the parent. Unfortunately, the own results indicate that parents do not provide first aid to burned children correctly. The most common

The aim of prehospital care is stabilizing ABCDEs (airway, breathing, circulation, disabilities, and environment control), preventing ongoing burn injury and provision of analgesia, cover-

It is worth to underline that also first aid provided by medical stuff in the place of the injury is not correct. The situation seems surprising, because in Poland young doctors are trained in

Nessler et al. conducted the pilot study (the anonymous questionnaire) among young doctors in Malopolska region (Poland) to evaluate the knowledge of burn first aid, because many patients admitted to burn centers in Poland receive inadequate treatment just after burn injury. The questionnaire verified the respondents' knowledge about appropriate first aid provided several minutes after burn trauma and included questions about possibilities of actions after

tion until the patient has been placed under appropriate medical care [2].

mistakes were no cooling the burn wound and no analgesics used [13].

ing area involved, and rapid transfer to emergency department [9].

first aid (including first aid in burns) during studies.

from single parent families [12].

282 Essentials of Accident and Emergency Medicine

ate facility for medical care [2].

tion time, and results in better esthetic scar.

**6. First aid in burns**

Care for burned pediatric patient is a challenge for medical and paramedical staff. Treatment of burns is multidisciplinary. According to Juan P. Barret and David N. Herndon, in the burn team, apart from surgeons who specialize in the treatment of burns (general, pediatric, and plastic surgeons), should work also nurses (experienced with care for burned patients), intensive care professionals, scrub and anesthesia nurses, case managers (acute and reconstructive), anesthesiologists, respiratory therapists, rehabilitation therapists, dietitians, psychosocial experts, social workers, volunteers, microbiologists, research personnel, quality control personnel, and workers of support services [1].

The triage decision is based on the extent of burn, body surface area involved, type of burn, associated injuries, any complicating medical or social problems, and availability of ambulatory management [4].

In addition to what has been mentioned above, the criteria that are taken into account to decide if the patient requires hospitalization or referral to the center of burns are anatomic location of the injury and age of the patient.

The most important aspect in pediatric population is age—all the children younger than 1 year old should be hospitalized. Moreover all patients with third-degree burns should be treated in the hospital. Apart from depth of the injury, also extension of burn is taken into account. Hospitalization should be considered in children from families with lower socioeconomic status. Pediatric patients with burns on the face, hands, feet, genitalia, perineum, and joints; all patients with inhalation injuries and electrical or chemical burns; and also patients with associated injury should be hospitalized. Moreover, each patient with suspected nonaccidental injury should be admitted to the hospital. In Poland children with burns are hospitalized in departments of pediatric surgery (with personnel educated about care of burnt patients) or burn centers (children with major burns).

It is possible to classify burn injury according to the severity into minor, moderate, and major [1]. Patients with moderate and major burns require hospital treatment. Minor burns are burns covering less than 15% total body surface area in adults and less than 10% total body surface area in children; less than 3% total body surface area is full-thickness burn; they do not involve the head, feet, hands, or perineum [1]. Moderate burns are burns covering 15–25% total body surface area in adults and 10–15% total body surface area in children, full-thickness burns 3–10% total body surface area, and superficial partial-thickness burns of the head, hands, feet, or perineum [1]. Each case of suspected child abuse is classified as moderate burn [1]. Moreover, in this group, all patients have burn injury and concomitant trauma, significant preexisting disease, and extreme age (neonate and infants). Major burns cover more than 25% total body surface area in adults and more than 15% total body surface area in children [1]. In this group are full-thickness burns of more than 10% total body surface area, deep burns of the head, hands, feet, and perineum, inhalation injuries, chemical burns, and electrical burns [1].

**8. Consequences of burns**

barrier to infective organisms [9].

increased evaporative water loss [10].

result in difficulties in eating and drinking [4].

impact of disfiguring burns [4].

The consequences of burns are mostly related with the loss of skin functions. The skin is the largest organ in the body and plays a crucial role in regulating body's temperature by preventing heat loss to the environment. It also prevents water loss from the body and acts as a

Problem of Burns in Children: Opportunities for Health Improvement

http://dx.doi.org/10.5772/intechopen.74490

285

It is important to underline the fact that children have a greater ratio of surface area to volume of the body, increased metabolic rate, increased heat loss (less fat and shivering), and

Possible complications of burns include variety of problems, for example, sepsis, hypovolemia, hypothermia, carbon monoxide poisoning, cyanide poisoning, gastric ulcers, cardiac dysfunction, hypermetabolic state, renal failure, transient antidiuresis, and anemia [4]. Another possible complication is laryngeal edema that can be treated with endotracheal intubation and tracheostomy [4]. Moreover, due to edema, compartment syndrome can develop, which means that the patient requires escharotomy [4]. Escharotomy technique involves making longitudinal incisions in segments with inelastic circumferential burns, usually of full thickness [1]. Possible contractures should be treated with physical therapy. Due to the risk of psychological trauma, it is important to provide to burn patients psychological rehabilitation [4]. The possible complications from respiratory system include pulmonary infiltrates, pulmonary edema, pneumonia, and bronchospasm [4]. Inhalation injuries may result in bronchospasm, airway inflammation, and impaired pulmonary function [4]. Moreover, they can

Among long-term consequences of burns in children are physical scarring and emotional

The risk of burn is the highest in children under 2 years old and in boys [5, 6]. Most of burns occur at home, when the child is under the supervision of parent. Appropriate supervision seems even more important than safe environment in prevention of burns in children [16].

Most of burns in children less than 2 years old occur when their mother or father is in the same room. The researchers found that family characteristics play a crucial role in increasing the likelihood of the injury. Lower maternal education, young age of mother and unemployment,

It is worth to underline that economic situation of the family is also important, because differences in the income result in differences in living conditions. The home environment plays an

Among effective strategies that reduce number of flame burns in pediatric population are

**9. Risk factors of burns in children: social, economic, and**

and lone parenthood are identified risk factors of burns in children [17].

important role in the risk of burn injury among children.

installation of smoke alarms and smoke detectors [16].

**environmental issues related with burns in children**

Initial treatment follows the ABCDEs of resuscitation. The aim is to stabilize the airway, breathing, and circulation [9].

Airway management should also include assessment for the presence of airway or inhalation injury [4]. In the cases of suspected airway burns, early intubation can be considered [9]. Children with stridor due to upper airway compromise also require urgent intubation [9]. Potential indications for ventilation are excessive burns that cover over 60–70% of total body surface area, full-thickness circumferential chest burns, and severe inhalation lung injury causing pulmonary edema and hypoxemia [9].

All children with burns over 20% of total body surface area should have intravenous access (peripheral access through non-burnt skin is preferred) [9]. Fluid resuscitation rates should be calculated using the time of burn, patient's body mass, and the surface of burn with the use, for example, of Parkland formula [9]. To determine the adequacy of fluid replacement, monitoring of urinary output is useful [9]. Some patients require nasogastric tube. Important issue in care of burned patient is analgesia.

The treatment of burns can be conservative and operative. Fortunately, most of children do not require surgical treatment, which is reserved for patients with deep (third degree) burns. Conservative treatment is indicated in children with superficial, partial-thickness burns.

Among the most often realized surgical procedures are escharotomy (rare), excision of the dead tissue, and skin grafting [1]. Escharotomy is indicated in patients with circumferential burns on the chest or limbs. The aim of escharotomy is to release the constrictive eschar. The burned skin should be released by incisions with electrocautery within the lines of escharotomy. Early excision of necrotic tissues and grafting is indicated in patients with full-thickness burns. In Poland burn wounds are covered with autografts (donor site is usually tight, less often scalp or back). Skin grafts can be split-skin grafts and full-thickness skin grafts. Most pediatric patients require split-skin grafts. Full-thickness skin grafts can be necessary in specific areas, such as the face (lips, eyelids, nose), hand/fingers, toes, and genitalia. In cases of extensive burns, it is possible to use meshed skin grafts.

Burn wound dressings play crucial role in the care for patient with burns. Burn dressing should protect the burn wound from further harm, such as desiccation, mechanical trauma, and infection. Moreover, they can facilitate the process of healing and relief pain [10]. The current literature is still inconclusive with regard to the gold standard burn dressing for the pediatric population [15]. In Poland burn wound is usually treated with silver sulfadiazine. However, it is commonly known that the ideal dressing for children should alleviate pain, decrease length of hospital stay, and minimize the risk of complications [15].


*Article* **Developing and Applying a Selection Model for Corrugated Box Precision Printing Machine Suppliers**

**Chin-Tsai Lin and Cheng-Yu Chiang \***

Department of Business Administration, Ming Chuan University, 250 Zhong Shan N. Rd., Sec. 5, Taipei 111, Taiwan<EMAIL_ADDRESS>
**\*** Correspondence<EMAIL_ADDRESS>Tel.: +886-04-2206-1660-630

**Abstract:** Corrugated box printing machines are precision equipment produced by markedly few manufacturers. They involve high investment cost and risk. Having a corrugated box precision printing machine (CBPPM) supplier with a good reputation enables a corrugated box manufacturer to maintain its competitive advantage. Accordingly, establishing an effective CBPPM supplier selection model is crucial for corrugated box manufacturers. This study established a two-stage CBPPM supplier selection model. The first stage involved the use of a modified Delphi method to construct a supplier selection hierarchy with five criteria and 14 subcriteria. In the second stage, an analytic network process was employed to calculate the weights of criteria and subcriteria and to determine the optimal supplier. According to the results, the five criteria in the model, in descending order of importance, are quality, commitment, cost, service attitude, and reputation. This model can provide insights for corrugated box manufacturers formulating their CBPPM supplier selection strategy.

**Keywords:** corrugated box printing machine; modified Delphi method; analytic network process (ANP); supplier

### **1. Introduction**

The global e-commerce market is rapidly developing, with exponential growth in online and TV shopping as well as demand for global shipping. Because most products purchased online or through TV shopping channels (e-commerce) are packaged using corrugated boxes for shipping, the development of e-commerce has contributed to the growth of the corrugated box industry. According to Smithers Pira [1], the global packaging market attained a value of US\$917 billion in 2019. Research and Markets (2019) revealed that the corrugated box market reached a value of US\$184.377 billion in 2019. Corrugated boxes have become the most adopted packaging materials in the packaging industry. With the continuous and rapid development of the e-commerce market, corrugated boxes, as the main packaging products, will inevitably grow rapidly accompanied with the development of the packaging industry, thus driving the rapid growth of the corrugated box precision printing machine equipment industry. For Tsao (2011) [2], the corrugated box precision printing machine is accompanied by the development of the corrugated box packaging industry. The main manufacturers of the corrugated box precision printing machine industry are currently concentrated in Europe, the United States, Japan, South Korea, Taiwan and China. Manufacturers with advanced production technology in Japan and Taiwan in the Asian region, mainly in the high-tech field, provide the best marketing and after-sales service system in the corrugated box printing machine manufacturers [3].

In the booming Internet and TV shopping consumption era, these consumer packaging have gradually become a visible part of people's lives. The increasing variety of consumer products and complexity of shipping methods have contributed to the importance of corrugated boxes as a packaging material. The demand for corrugated boxes is rapidly growing worldwide, contributing to the development of the corrugated box precision printing machine (CBPPM) industry. The sales value of the global CBPPM industry grew

**Citation:** Lin, C.-T.; Chiang, C.-Y. Developing and Applying a Selection Model for Corrugated Box Precision Printing Machine Suppliers. *Mathematics* **2021**, *9*, 68. https:// doi.org/10.3390/math9010068

Received: 20 November 2020 Accepted: 24 December 2020 Published: 30 December 2020

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional clai-ms in published maps and institutio-nal affiliations.

**Copyright:** © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

from US\$5.499 billion in 2014 to US\$7.312 in 2019, and the growth trend is expected to continue (Figure 1). As people's standard of living improves, they expect better appearance and quality of paper boxes rather than just basic paper box packaging. These expectations are closely related to the development of the CBPPM industry and spur market demands for corrugated boxes and for corrugated box precision printing machines.

**Figure 1.** Global market size of corrugated box printing machines [4].

Despite such a large business opportunity in the global CBPPM industry, global manufacturers face challenges such as high investment cost, long research and development (R&D) periods, consumer demand for customization, and high risk. Accordingly, the establishment of a decision-making model for the selection of CBPPM suppliers has become critical for corrugated box manufacturers to maintain their competitive advantage.

The selection of suppliers is a crucial but complex decision-making problem, and its ultimate goal is to find sustainable suppliers with the best potential of providing raw materials and components within a cost budget. According to Ptak and Schragenhiem [5], disruptions in the procurement process can undermine productivity, leading to serious consequences such as bad reputation caused by late delivery or the loss of customers. Therefore, suppliers play a crucial role in procurement activities. In the competitive global environment, most businesses have revisited their procurement strategy and established partnerships with their key suppliers. Despite its recognized importance, cost reduction is not the only critical factor. This study can provide insights into decision making strategies and sustainable operations that can be adopted by the CBPPM industry.

#### **2. Literature Review**

#### *2.1. Supplier Selection*

The selection of suppliers is critical. Having an appropriate supplier enables a company to offer competitive prices, deliver the correct quantity of products on time, produce high-quality products, and enhance its corporate image and reputation. Labib [6] considered product quality and delivery to be of greater importance than cost. Tam and Tummala [7] argued that the selection criteria for telecommunication service suppliers include quality, cost, problem-solving skills, expertise, delivery time, the ability to satisfy consumer needs, experience, and reputation. Liao and Kao [8] evaluated suppliers with the following criteria: depth of relationship, quality, shipping ability, guaranteed standard, and experience. Basnet [9] suggested that for both local and international businesses, quality, the ability to deliver on time, and performance are the most critical elements in supply chain management.

An excellent supplier satisfies a company's demands for raw materials, products, quality, and services. A company cannot find a high-quality and cost-efficient supplier without having a plan. A critical competency of a procurement specialist is to, by using

a rigorous and systematic method, find, evaluate, and select the most suitable supplier for a company [10]. Hsu [11] proposed the following evaluation methods for supplier selection: (a) benchmarking, (b) categorical method, (c) weighted-point method, (d) costratio method, and (e) unit total cost. Considering conflicts among supplier selection indicators, Shirouyehzad [12] employed a strengths–weaknesses–opportunities–threats analysis to evaluate suppliers qualitatively and quantitatively; Shirouyehzad used the technique for order performance by "similarity to the ideal solution" to determine the weights of indicators and adopted a linear planning method to allocate orders. Supplier evaluation methods fall into three major categories: qualitative analyses, quantitative analyses, and methods combining qualitative and quantitative analyses.

Chin [13] defined suppliers as business entities that provide products or services to a buyer and charge the buyer with remuneration in return; such provision encompasses raw materials, equipment, tools, and other resources. The management of suppliers involves active attitudes gradually established in the process of communication and interaction with the suppliers [14]. Shima Aghai [15] proposed a fuzzy multiobjective planning model that incorporates a wide range of factors, namely qualitative, quantitative, risk, and volume discount factors, in supplier selection; this model can be used to select suppliers and optimize supply volume. Supplier selection largely determines subsequent endeavors of establishing buyer–supplier partnerships and increasing supplier capabilities through supplier development programs [16]. The importance of this process for companies is reflected in the final price of products. The price of raw materials, as the main part of the product, is crucial [17,18]. Supplier selection is among the key tasks of supply management [19]. Accordingly, this study constructed a supplier selection model suitable for CBPPM suppliers to help companies maintain competitive advantage.

#### *2.2. Analytic Network Process*

The analytic network process (ANP) involves using pairwise comparisons to reveal the relative importance of decision-making features at each level on a 1–9 ratio scale. Establishing a pairwise comparison matrix, calculating the eigenvalue and eigenvector, and conducting a consistency test can avoid evaluation accuracy being undermined by the decision maker's adoption of multiple criteria. The levels are then aggregated to yield a priority vector of the relative importance of alternatives; subsequently, the optimal alternative is determined according to their relative weights as indicated in the vector. ANP, whose theory and application were introduced by Saaty [20], is derived from the analytical hierarchy process (AHP) and is aimed at solving problems involving dependence and feedback among elements in decision making. Overall, the ANP is a mathematical theory capable of solving dependence and feedback problems systematically.

The ANP comprises four steps: (1) constructing a hierarchical structure of the problem, (2) establishing the pairwise comparison matrix and calculating the eigenvector, (3) obtaining the supermatrices and weights, and (4) determining the optimal alternative.

#### Step 1: Constructing a Hierarchical Structure of the Problem

Determine the decision-making problem and construct a hierarchical structure for the problem; and describe the problem in detail and divide it into a hierarchical network.

Saaty [21] divided the ANP into two parts. The first part involves evaluating the network relationships between criteria and subcriteria; these relationships affect the relationships within a system. The second part is constituted by the network relationships between elements and clusters. According to a network system can be divided into various clusters to form a complex network structure. Figure 2a,b conceptualizes the AHP and ANP, respectively. Saaty [20] presented the interdependent relationships between clusters and elements in a diagram and used arrows to indicate relationships and interaction between them. For example, Figure 2b depicts interdependent elements.

**Figure 2.** Conceptual diagrams of the analytical hierarchy process (AHP) and analytic network process (ANP) [22].

Step 2: Establishing the Pairwise Comparison Matrix and Calculating the Eigenvector

Saaty [20] recommended the use of the 1–9 ratio scale in pairwise comparison. In ANP pairwise comparisons, the limiting influence of each criterion is calculated to establish the supermatrices.

The pairwise comparison matrix (A) is formed by experts making pairwise comparisons between criteria. Through a hierarchical analysis, the eigenvector (W) of the maximum eigenvalue (*λ*max) is obtained to satisfy the equation A × W = *λ*max × W. Then, *λ*max can be used to calculate the consistency index (CI); a satisfactory consistency level is indicated by CI ≤ 0.1. According to Saaty [23], a CI < 0.1 suggests the judgments made by experts are consistent. CI and consistency ratio are calculated using the following equations:

$$\text{CI} = \frac{\lambda\_{\text{max}} - \mathbf{n}}{n - 1} \tag{1}$$

$$\text{CR} = \frac{\text{CI}}{\text{RI}} \tag{2}$$

RI = random index.

Step 3: Obtaining the Supermatrices and Weights

The supermatrices comprise an unweighted supermatrix, a weighted supermatrix, and a limiting supermatrix, which can be used to obtain the weights of criteria and subcriteria.

A supermatrix is composed of various submatrices, and each ratio scale in the submatrices represents the influence of elements in a cluster on elements in other clusters (i.e., outer dependence) or on other elements in the same cluster (i.e., inner interdependence). Finally, the criteria and subcriteria of all dimensions are listed (respectively) at the left and top of a matrix to form a complete supermatrix, as shown in (3).

Because an unweighted supermatrix (W) may not be column-stochastic (i.e., each column does not sum to (1), it must be converted using the following process. No conversion is needed if the dimension column is stomatic (sum = 1). For nonstochastic columns, relative importance is applied on the submatrix of criteria columns to obtain the weighted supermatrix (W'). Subsequently, the supermatrix is subject to a limiting process, namely raising W' to the power of 2k + 1 (k is an arbitrarily large number) until the interdependent relationships converge, to obtain the relative weights of criteria [20].

As an example, the following is the supermatrix (W*h*) of a three-level hierarchical structure [20]:

$$\mathbf{W}\_{\rm li} = \begin{bmatrix} 0 & 0 & 0 \\ \mathbf{W}\_{21} & 0 & 0 \\ 0 & \mathbf{W}\_{32} & I \end{bmatrix} \tag{4}$$

where W21 is the eigenvector of criteria under the decision-making goal, W32 is the eigenvector of the pairwise comparison matrix between alternatives under each criterion, and *I* is the identity matrix; a 0 indicates the relationship between identical or two independent elements or criteria without interdependences.

For interdependent criteria, a network structure must be used in place of a hierarchical structure. Accordingly, the supermatrix is updated to W*n* in (5), where W22 represents the interdependence of the criteria [20].

$$\mathbf{W}\_{\overline{n}} = \begin{bmatrix} 0 & 0 & 0 \\ \mathbf{W}\_{21} & \mathbf{W}\_{22} & 0 \\ 0 & \mathbf{W}\_{32} & \mathbf{W}\_{33} \end{bmatrix} \tag{5}$$

This study employed the *ANP* to obtain the weights of elements and weights. Therefore, Wn must be modified as W *n*, as presented in (6).

In (6), W22 and W33 respectively represent the interdependence weights of the elements and criteria.

$$\mathbf{W'}\_{\mathbf{n}} = \begin{bmatrix} 0 & 0 & 0 \\ \mathbf{W}\_{21} & \mathbf{W}\_{22} & 0 \\ 0 & \mathbf{W}\_{32} & \mathbf{W}\_{33} \end{bmatrix} \tag{6}$$

The exponent of the matrix reaches an extremum where the matrix converges, thus the extremum holds constant. To achieve matrix convergence, the weighted supermatrix is raised to the power of 2*k* + 1, where *k* → ∞, as in (7). This yields a new matrix, the limiting supermatrix (W*ANP*; [20]), and the finalized weights of criteria and subcriteria can then be obtained.

$$\mathcal{W}\_{ANP} = \lim\_{k \to \infty} \left(\mathcal{W}'\_n\right)^{2k+1} \tag{7}$$

Step 4: Determining the Optimal Alternative

According to the limiting supermatrix W*ANP* in (7), the weights can be obtained through multiple matrix calculations. These weights are then used as the basis for arranging the priority of alternatives.

#### **3. Proposed Model**

This study established a two-stage CBPPM supplier selection model. In Stage 1, a modified Delphi method and content validity ratio were used to determine the criteria and subcriteria for supplier selection as well as the interdependence between criteria and subcriteria. In Stage 2, the ANP was used to calculate the weights of criteria and subcriteria. The two-stage supplier selection model is as follows [24–26]:

### *3.1. Stage 1: Establish a Hierarchical Network*

This stage involves the use of the modified Delphi method comprising four steps, as follows [27,28]:

### *3.2. Stage 2: Select the Optimal Supplier with the ANP*

This stage involves the four steps of ANP, as follows [18]:

#### **4. Results and Discussion**

SUNRISE, established in 1996 with a capital of NT\$150 million, is a CBPPM manufacturer that sells machines mostly to paper box manufacturers in Taiwan, China, Europe, Southeast Asia, Middle America, and the Middle East. With a revenue of US\$36 million in 2019, it is now the largest CBPPM manufacturer in Asia and the second largest in the world. It has thus become the hidden champion of the industry in the Taiwanese market, with patents in various countries. The high-capacity fixed-type CBPPM is its most precise, expensive, and sold machine. This CBPPM (Figure 3), which can print more than 300 color corrugated boxes per minute, contributes nearly 35% of the company's revenue (http://www.sunrisemachinery.com) [29].

**Figure 3.** High-capacity fixed-type corrugated box precision printing machine (CBPPM) (http: //www.sunrisemachinery.com).

The CBPPM industry is relatively closed compared with other industries in Taiwan. Despite the enormous business opportunity in CBPPM manufacturing, no more than 30 CBPPM manufacturers exist in Taiwan. The R&D of CBPPMs involve an extremely high cost and a 3–5-year period (or longer). The R&D and sales expenses for a CBPPM total more than US\$3 million. Although a new CBPPM has a product life cycle of more than 10 years on

average, its high investment cost and slow return on investment discourage new investors. The industry also has high entry barriers because it involves (1) complex and specialized technologies, (2) specialized assembly technicians who require extensive training, and (3) a high level of working capital. A monthly working capital of more than US\$120 million is required for the warehousing of components alone. Accordingly, procurement plays a critical role in the operation of a CBPPM manufacturer, which must establish a collaborative supply chain management system that integrates upstream and downstream suppliers well to shift from the red ocean strategy—which focuses on competition and price cuts—toward the blue ocean strategy, manufacturing products of high value at low cost [30].

This study adopted SUNRISE as an example and optimized its supplier selection process for the five firms that supply the most electronic control components to it. The optimization was conducted using the modified Delphi method and ANP to verify the feasibility of the study's proposed supplier selection model based on these two methods.

This study used the five firms as alternatives to conduct a supplier selection process as follows.

#### *4.1. Stage 1: Establish a Hierarchical Network*

#### Step 1: Define the Criteria

Six key members of SUNRISE (board director, director of plant operations, chief R&D officer, chief procurement officer, junior procurement officer, and procurement specialist) were invited to determine 11 criteria and 64 subcriteria for the supplier selection (Table 1).

**Table 1.** Criteria and subcriteria determined by six key members of SUNRISE.

**Table 1.** *Cont.*

Step 2: Convene an Expert Panel

According to Murry and Hammons [28], the appropriate size of an expert panel is more than 10 members, but an excessively large panel (with more than 30 members) can complicate the research work and create difficulty for the panel to reach a conclusion. On this basis and in consideration of feasibility and available research resources, the present study determined that the expert panel size be 23 members from the industry, government, and academia (Table 2).

#### **Table 2.** Composition of the expert panel.

Six manufacturers were interviewed; four completed a questionnaire.

#### Step 3: Conduct a Questionnaire Survey on the Panel

The first survey was administered to 23 experts who expressed their willingness to participate through mail; 20 questionnaire responses were returned for a response rate of 86.96%. Subsequently, a second survey was administered to the 20 experts (i.e., excluding the three who did not return a response) along with statistical charts for the first survey. In the second survey, 20 questionnaires were distributed, and all were returned. This study employed a two-round modified Delphi method, repeating the administration of the survey until consensus was established (Table 3).

**Table 3.** Comparison of survey response rates in the two-round modified Delphi method.

Step 4: Determine the Standard of Consistency within the Panel

After a preliminary version of the questionnaire was created, the modified Delphi method was used to verify its content. A total of 20 experts from industry, government, and academia were recruited to determine the validity of the items. The experts were asked to rate each item on a 5-point Likert scale (1 = *Very dissatisfied* to 5 = *Very satisfied*) according to its appropriateness and relevance to the research topic as well as to determine the importance of each criterion and subcriterion. The content validity ratio (CVR) formula proposed by Lawshe [31] was employed to calculate the level of agreement among the experts. The ratings were used to calculate the CVR; in this study, a rating = 5 was determined to be the standard. Specifically, the CVR for each expert was calculated by dividing the number of items rated as 5 points by the total number of items. The CVRs for the 20 experts ranged between 0.7 and 1.00. This indicated the content validity of the questionnaire, with an average CVR ≥ 0.7 [32].

After deleting criteria and subcriteria with a CVR < 0.7, five criteria and 14 subcriteria remained. The five criteria were quality, commitment, cost, service attitude, and reputation. The 14 subcriteria were product reliability, quality management system for substandard products, commitment to orders, stable supply, accuracy and reliability, on-time delivery, price reduction, price competitiveness, attitude, ability to manage customer complaints, negotiation with suppliers, after-sales services, integrity, and profit increase. On the basis of the experts' input, the criteria were interdependent (Figure 4); inner interdependence was present between subcriteria (Table 4). According to these results, the CBPPM supplier selection hierarchical network was established (Figure 5).

**Figure 4.** Relationships among CBPPM supplier selection criteria.

**Figure 5.** Hierarchical network for CBPPM supplier selection.

### *4.2. Stage 2: Select the Optimal Supplier with the ANP*

Step 1: Establish the Pairwise Comparison Matrix

A panel of 20 experts was convened to determine the relative importance of each criterion in the ANP questionnaire. Table 5 depicts the resulting pairwise comparison matrix W21.

(1) *λ*max = 5.2394; (2) CI = 0.0598 and consistency ratio (CR) = 0.0534 ≤ 0.1.

Step 2: Calculate the Eigenvalue and Eigenvector

Super Decisions software was used to calculate the maximum eigenvalue *λ*max = 5.2394 and corresponding eigenvector *x* = (0.4206, 0.2827, 0.0985, 0.0655, 0.1327, rightmost column of Table 5) for the pairwise comparison matrix.

Equations (1) and (2) were used to obtain CI = 0.0598 and CR = 0.0534, both of which indicate satisfactory consistency.

Step 3: Form the Supermatrix and Obtain the Weights

After calculating the weights for W21, the eigenvector matrix W32 was formed. For example, the pairwise comparison matrix and eigenvector for subcriteria *C*11 and *C*12 under criterion *C*1 are presented in Table 6. Table 7 compiles W21 and W32.

**Table 6.** Pairwise comparison matrix and eigenvector for subcriteria under criterion *C*1.

(1) *λ*max = 2.0000; (2) CI = 0 and CR = 0 ≤ 0.1.

**Table 7.** Weights for criteria and subcriteria.

Matrix W22 represents the pairwise comparison results for the five criteria with the presence of inner interdependence. The eigenvector matrix formed with the eigenvectors is shown in (8). Matrix W33 is the eigenvector matrix representing the pairwise comparison results for the 14 subcriteria with the presence of inner interdependence, as presented in (10).

An unweighted supermatrix is formed by combining matrices W21, W22, W32, and W33, as expressed in (9). Table 8 reveals the details of the supermatrix. In this study, matrices W22 and W32 are each assigned a weight of 0.5 to obtain the weighted supermatrix (Table 9).

Table 10 illustrates the limiting supermatrix, and Equation (11) provides the weights of all subcriteria (W*ANP*) [33].

$$\mathbf{W}\_{\boldsymbol{n}} = \begin{bmatrix} 0 & 0 & 0 \\ \mathbf{W}\_{21} & \mathbf{W}\_{22} & 0 \\ 0 & \mathbf{W}\_{32} & \mathbf{W}\_{33} \end{bmatrix} \tag{9}$$

(11)

Table 11 lists the weights of the five alternatives calculated according to the pairwise comparison matrix for subcriterion *C*12 (quality management system for substandard products).

**Table 11.** Weights of the five alternatives calculated using the pairwise comparison matrix for subcriterion *C*12.

(1) *λ*max = 5.3250; (2) CI = 0.0598 and CR = 0.0534 ≤ 0.1.

Table 12 presents the weights of the five alternatives calculated using the pairwise comparison matrices of all subcriteria.

**Table 12.** Eigenvectors of five alternatives under each criterion.

Step 4: Select the Optimal Procurement Alternative

On the basis of (11) and Table 12, the priority vector of the five alternatives is obtained, as shown in (12).

According to (12), in the supplier selection process, the companies were ranked as follows: Company D (0.2801), Company E (0.2388), Company A (0.1923), Company B (0.1532), and Company C (0.1356; Figure 6).

**Figure 6.** Ranking of alternatives for supplier selection.

#### **5. Conclusions**

The continuous, rapid development of the e-commerce market has contributed to fast growth in the packaging industry and is allowing the CBPPM industry to thrive. Accordingly, the establishment of an appropriate CBPPM supplier selection decisionmaking model has become critical for corrugated box manufacturers to maintain their competitive advantage.

According to the empirical results, Labib [6] considered product quality and delivery to be of greater importance than cost. Basnet [9] suggested that for both local and international businesses, quality, the ability to deliver on time, and performance are the most critical elements in supply chain management. Tam and Tummala [7] argued that the selection criteria for telecommunication service suppliers include quality, cost, problem-solving skills, expertise, delivery time, the ability to satisfy consumer needs, experience, and reputation. Four of the criteria obtained in this study are quality, commitment, cost and reputation, which is the same as Tam and Tummala [7], the new model is of high practical value and enables enterprises to consider and evaluate alternative solutions from multiple perspectives, thus facilitating sustainable operation and development. A quality-oriented company has an influence from higher managers to the employees of different functional departments. It not only can prevent the problems facing the products but also improve the current situation continuously. A corporate culture of having quality as the first priority has always been regarded as one of the main elements of a successful implementation of total quality management.

Through a rigorous research design, this study formed a panel of experts to build a CBPPM supplier selection model, offering insight for the corrugated box industry. The following conclusions were drawn:

products (0.1139), two of which belonged to the "quality" criteria. A CBPPM manufacturer can face an enormous loss if it manufactures products using substandard components. Scrupulous product inspection and component control practices guarantee a long, useful life and high quality of machines, which in turn enhances the manufacturer's commitment, service attitude, and reputation.

**Author Contributions:** Conceptualization, C.-T.L. and C.-Y.C.; methodology, Analytic Network Process (ANP); software, SuperDecisions; validation, C.-T.L. and C.-Y.C.; formal analysis, C.-T.L.; investigation, C.-Y.C.; resources, C.-T.L.; data curation, C.-Y.C.; writing—original draft preparation, C.-Y.C.; writing—review and editing, C.-Y.C.; visualization, NA; supervision, C.-T.L.; project administration, C.-Y.C.; funding acquisition, NA. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Data Availability Statement:** We fully adhere to its Code of Conduct and to its Best Practice Guidelines.

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

#### **References**


**1. Introduction and relevance of the topic**

The last global financial crisis was set-up by risky mortgage backed security loans and triggered by the default of the Lehman Brothers Holdings in September 2008. This marked the beginning of many policy measures and changes. While central banks around the world began to decrease interest rates in order to boost the economy, stock markets soared. At the same time, the internet is becoming more and more a medium for global interconnection due

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

to technological advancements across all industries. Not only more people connect to the internet every day, also devices actively communicate with one another, coined under the term "the internet of things". Moreover, recent initial public offerings of well-known internet companies such as Groupon, LinkedIn, Facebook, Alibaba Group Holding Limited and funding support programs in the United States, the European Union and China drive the interest of investors for lucrative opportunities.

When looking at the development of certain equity indices in the United States, Germany and China, the rates show record or close to record peaks as seen on **Figure 1**. For the Nasdaq Composite Index such rates were last seen during the dot-com bubble while the Deutscher Aktien Index 30 is almost twice as high as during the dot-com bubble and before the recent financial crisis of 2008. For the China Securities Index 300, the sources from the Bloomberg database even state price-to-earnings ratios as high as 220 times reported profits.

Bringing these circumstances into a global context, an artificial economic boost was created after the crisis that made equity indices soar—just like before the dot-com bubble. Hence, the question arises how the situation as of December 2015 is different if it is at all. Are there signs of an asset price bubble as some research argues [1, 2]?

The dot-com bubble is one of the most disputed bubbles that occurred in the last decades. Each bubble can be modelled according to some rules. Welfare analysis with empirical prediction is subject to examine [3]. Also, the pure statistical tests are suitable to describe bubble [4]. But alternative assessment can be provided by another angle of view on bubbles [5]. Moreover, market bubbles are related to market volatility in general [6].

**Figure 1.** Increase of indices' values across regions. Source: Own elaboration by the authors.


**Meet the editor**

Dr. Chih-Pin Liu is a Professor, in Department of Diabetes and Metabolic Diseases and Department of Immunology, at Beckman Research Institute of City of Hope. He received his B.S. degree from National Taiwan University, and Ph.D. degree from University of Wisconsin-Madison, followed by postdoctoral fellowships at Beth Israel Hospital/Harvard Medical School in Boston

and at National Jewish Medical and Research Center in Denver. He has had long-standing research interest in understanding the mechanisms that regulate immune tolerance induction during type 1 diabetes development. His recent work has focused on using genome-wide approaches to understand the molecular mechanisms responsible for modulating the function of regulatory T cells and identifying gene targets to improve regulatory T cell function for immunotherapy.

Contents

**Preface IX**

**Part 1 Diabetes Mellitus and Complications 1**

Vladimir Jakus, Jana Kostolanska, Dagmar Michalkova and Michal Sapak

Chapter 2 **Diet, Lifestyle and Chronic Complications in Type 1 Diabetic Patients 21**

Chapter 3 **Lipid Disorders in Type 1 Diabetes 45**

**Part 2 Psychological Aspects of Diabetes 83**

Chapter 5 **Type I Diabetes in Children and Adolescents 85**  Laura Nabors, Phillip Neal Ritchey, Bevin Van Wassenhove and Jennifer Bartz

Bruno Vergès

Chapter 1 **The Study of Glycative and Oxidative Stress in Type 1**

S.S. Soedamah-Muthu, S. Abbring and M. Toeller

Chapter 4 **Prevalence of Type 1 Diabetes Correlates with Daily Insulin**

Chapter 6 **Inadequate Coping Attitudes, Disordered Eating Behaviours and Eating Disorders in Type 1 Diabetic Patients 95**

Ricardo V. García-Mayor and Alejandra Larrañaga

Chapter 7 **Predictors of Adherence, Metabolic Control and Quality of Life in Adolescents with Type 1 Diabetes 119**

> M. Graça Pereira, A. Cristina Almeida, Liliana Rocha and Engrácia Leandro

**Dose, Adverse Outcomes and with Autoimmune Process Against Glutamic Acid Decarboxylase in Adults 61**  Mykola Khalangot, Vitaliy Gurianov, Volodymir Kovtun, Nadia Okhrimenko, Viktor Kravchenko and Mykola Tronko

**Diabetes Patients in Relation to Circulating TGF-Beta1, VCAM-1 and Diabetic Vascular Complications 3**