**1. Introduction**

Surgical approaches to the cervical spine include anterior, posterior, trans-oral, lateral trans-mandibular which can be done by open, tubular MIS or full endoscopic as described recently.

Anterior cervical spine surgery is commonly performed for the treatment of varieties of cervical spine pathologies that include degenerative, trauma, tumors, deformities and infections [1].

Techniques of anterior cervical spine surgery include anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), for primary stability and fusion different type of devices are used, such as cages, plates, cylinders, as well as bone growth promoters, substitutes, and bone morphogenic protein (BMP) have been use. In selected cases, discectomy alone is also performed especially through MIS or endoscopic techniques [2].

Anterior cervical discectomy and fusion (ACDF) was first described by Smith Robinson in 1968, when he performed discectomy and fusion was done using tricortical bone graft, during 1990s more than 500,000 anterior cervical discectomy and fusion (ACDF) was done in USA [3].

Anterior cervical spine surgery is safe and effective harboring a wide range of indications with a low rate of morbidity and mortality [4]. Complications following anterior cervical spine surgery include airway complications, dysphagia, dysphonia, infection, implant failure, non-union, neurological deficit, vascular injuries, implant subsidence, adjacent level disease and even death [5–10].

Dysphagia is one of the most common complications following anterior cervical spine surgeries, dysphagia is a symptom indicative of an abnormality in the neural control of, or the structures involved in, any phase of the swallowing process, which involve both voluntary and involuntary/reflex responses. Oropharyngeal dysphagia is an impairment in the speed and/or safe delivery of food materials from entry in the mouth to the upper portion of the esophagus. If present, the patient is at an increased risk of

#### *Dysphagia - New Advances*

aspiration and may be unable to swallow properly liquids, foods, or saliva. The condition is considered long standing if it is still present more than 4 weeks after surgery [11].

Dysphagia following anterior cervical surgery can occur in the three phases of swallowing process (oral & transport phase, pharyngeal & esophageal) [12].


Identification, Knowledge Engineering and Digital Modeling for Adaptive and Intelligent Control

Edited by Natalia Bakhtadze, Igor Yadykin, Andrei Torgashov and Nikolay Korgin

www.mdpi.com/journal/mathematics


**Elena Fortunati 1,\*, Geremia Giovanale 2, Francesca Luzi 1, Angelo Mazzaglia 2, Josè Maria Kenny 1, Luigi Torre 1 and Giorgio Mariano Balestra 2,\***

Academic Editors: Stefano Farris and Lluís Palou Received: 28 August 2017; Accepted: 9 November 2017; Published: 11 November 2017

**Abstract:** Kiwifruits and romaine lettuce, among the most horticulturally-consumed fresh products, were selected to investigate how to reduce damage and losses before commercialization. The film-forming properties, physico-chemical, and morphological characteristics, as well as the antimicrobial response against *Botrytis cinerea* and *Pectobacterium carotovorum* subsp. *carotovorum* of chitosan hydrochloride (CH)-based coatings were investigated. The results underlined the film-forming capability of this CH that maintained its physico-chemical characteristics also after dissolution in water. Morphological investigations by FESEM (Field Emission Scanning Electron Microscopy) underlined a well-distributed and homogeneous thin coating (less than 3–5 μm) on the lettuce leaves that do not negatively affect the food product functionality, guaranteeing the normal breathing of the food. FESEM images also highlighted the good distribution of CH coating on kiwifruit peels. The in vitro antimicrobial assays showed that both the mycelial growth of *Botrytis cinerea* and the bacterial growth of *Pectobacterium carotovorum* subsp. *carotovorum* were totally inhibited by the presence of CH, whereas in vivo antimicrobial properties were proved for 5–7 days on lettuce and until to 20–25 days on kiwifruits, demonstrating that the proposed coating is able to contrast gray mold frequently caused by the two selected plant pathogens during postharvest phases of fruit or vegetable products.

**Keywords:** chitosan hydrochloride; coating; edible film; food safety; postharvest; antimicrobial properties; *Botrytis cinerea*; *Pectobacterium carotovorum* subsp. *carotovorum*; rotting


**8. Conclusion**

reported an improvement in confidence and performance after ECMO simulation training. Su et al. reported a faster deployment time to ECPR initiation after simulation training [14], and Allan et al. reported a decrease in cannulation time for ECPR in pediatric cardiac surgery trainees [15]. Recently, Zakhary et al. published the first randomized controlled trial comparing the performance after conventional water-drill training and simulation training. In this study, the simulation training group had a higher scenario score and a shorter time to critical action in certain scenarios. More importantly, this superior performance was sustained over 1 year [16]. However, it must be noted that despite the ongoing research and implementation of simula-

Percutaneous cannulation for ECMO is increasingly performed by intensivists, cardiologists and emergency physicians. Despite infrequent occurrences, complications of cannulation may be associated with significant morbidity and mortality [17]. Existing simulation models mainly focus on ECMO circuit management, with less emphasis on percutaneous cannulation, and there are yet publications related to percutaneous cannulation model. Collaborative international endeavours targeted to improve cannulation safety are in progress. We have developed a simulation model for fluoroscopic-assisted dual-lumen cannulation (https://www.youtube.

Despite the increasing use of simulation in many ECMO education programmes, the role of simulation remains unclear in currently available guidelines and international recommendations. The latest Extracorporeal Life Support Organization (ELSO) guideline on ECMO specialist training published in 2010 only included didactic lectures, water drills, animal laboratory sessions and bedside training as the main training modalities. Moreover, it only targeted 'ECMO specialists' (i.e. nurses, respiratory therapists, perfusionists and medical professions providing care under the guidance of ECMO physicians) and not ECMO

In a United States survey published in 2015, simulation has been adopted as part of the institutional ECMO credentialing programme for ECMO physicians in 73% of the centres, highlighting its increasing importance [18]. The EuroELSO guidelines for training and continuing education of ECMO physicians published in 2017 have incorporated high-fidelity simulation training as an alternative training modality to supplement bedside clinical hours. More importantly, its significance in teamwork and communication skills training has been acknowledged [19]. It is expected that the role of simulation will be further expanded in future

As mentioned earlier, ECMO training curriculum and thus simulation programmes are institutional specific and may be modified according to the characteristics and training needs of the institution. As a result, significant variances exist among different institutions, imposing difficulties in standardization and validation of the assessment tools. Currently, there are no validated assessment tools to assess the learning efficacy of common and essential ECMO scenarios. Joint efforts are ongoing among international ECMO educators to develop

com/watch?v=dr02RAMRk1A) and two-cannula cannulation in veno-venous ECMO.

tion training, there is yet evidence of association with better patient outcomes.

**7. Challenge and future directions**

144 Advances in Extra-corporeal Perfusion Therapies

physicians.

versions of the ELSO guideline.

ECMO is a low-volume but highly complex technology. The management of ECMO patients often requires an integration of cognitive, psychomotor and behavioural skills that can be addressed by simulation training. As a result, simulation is increasingly acknowledged as one of the essential learning tools in ECMO education. Further researches in simulation technology, medical science pedagogy and clinical trials are warranted to delineate its impact on patient outcomes.


**1. Introduction**

With the emergent strategic concern of environmental protection, organizations nowadays are expected to be responsible for green management. Thus, strategic HRM as a framework linking elements of HRM with strategic goals and objectives is expected to play a pivotal role in fostering employees' pro-environmental behavior and in achieving sustainability of the overall organizational system (people, environment, and practices) [1, 2].

In this regard, companies strive to develop innovative environmental processes that will have significant implications for management and that are able of making employees environmentally aware, involved, and highly trained. Consequently, HRM needs to ensure that targeted HRM programs are designed and developed to raise employee awareness of the importance of environmental initiatives, develop the workforce skills as well as engage it in the corporate green goals.

Several businesses have employed a strategic tool known as green human resources management (GHRM) [3]. Masri and Jaaron [4] define GHRM as the use of human resources management practices to reinforce environmentally sustainable practices and to increase employees' commitment to the issues of environmental sustainability. Thus, with companies now changing their business strategies and efforts toward a more environmentally focused agenda; HR must adjust its mandate and expand its scope by incorporating environmental management into its core HR functions [5].

Green HR practices result in different outcomes, such as improved employee moral, stronger public image, increased employee loyalty, increased brand recognition, competitive advantage, increased workforce productivity, and increased employee retention [6].

Despite the previous literature, numerous issues remain misunderstood. Scholars have not given adequate attention to how GHRM contributes green competitiveness of the firm. It presents a major gap for scholars in green management to be filled [7]. Hence, the current study aims to bridge the gap between previous studies by expanding the understanding of how GHRM can lead to a green competitive advantage. This analysis draws on the resource-based view (RBV) and suggests that only companies with advanced personnel management in environmental issues will be able to gain a competitive advantage associated with improved green knowledge, enhanced green values, and environmentally committed employees. This paper is among the first works to deal with such a complex framework that considers the interrelationships among numerous constructs and their effects on green competitive advantage.

The present study argues that companies need to develop a GHRM that possesses both greenness and involvement attributes to improve competitive advantage in the environmentally friendly business era. Besides, one of the key elements for green competitive advantage is knowledge, commitment, and values. By increasing these three assets, workers would actually be conscientious, active, and committed to the company's environmental goals, which further contributes to the corporate environmental activities' success. The primary objectives of this study are:


The Sarcin–Ricin Loop

The sarcin–ricin loop is one of the most conserved rRNA regions of the ribosome, which underlines its importance in ribosome function. It is located in helix 95, in domain VI of 23S/25S/28S rRNA (nucleotides 2646-2674 in *E. coli*, 3012-3042 in yeast) (Figure 2A).

**Figure 2.** The model of sarcin–ricin loop structure. (**A**) Alignment of highly conserved secondary structures of yeast and *E. coli* SRL. The red color indicates the key adenine hydrolyzed by the ricin. A conserved fragment of 12 nucleotides is marked with a gray color. (**B**) Structure of the *S. cerevisiae* SRL (PDB code 3U5H). The key adenine was marked in red (A3027). The individual structural elements of the SRL - the stem, the flexible region, the G-bulged cross-strand stack with the highlighted individual nucleotides and the GAGA loop - are marked with a dotted black line. The gray fields show the non-canonical π-stacking interactions between particular bases. Model prepared by PyMol software, (The PyMOL Molecular Graphics System, version <IP_ADDRESS>, Schrödinger, LLC, NY, USA) based on [42].

Unlike other rRNA regions, which form compact structures coordinated by rRNA–rRNA or rRNA-protein interactions, the SRL exists on the ribosome as an autonomous unit [43–45] and is exposed to the solvent [46]. This unique feature is critical for its accessibility for external factors like trGTPases. From the structural point of view, the SRL has the conformation of a distorted hairpin [47]. It consists of several well-organized elements (Figure 2B) [48]: the stem, the flexible region, the G-bulged cross-strand stack, and the GAGA loop [45] with the key adenine base (A2660/A3027—*E. coli*/*S.cerevisiae* numbering), which is a target for ricin activity. The SRL stem structure is formed mainly by classical Watson–Crick base pairs, whereas the rest of the structure is stabilized mainly by π-stacking interactions. The critical element, the GAGA tetra-loop, forms a compact well-organized structure [43]. The spatial organization of the loop structure is determined by non-canonical interactions between base pairs, allowing the carbohydrate-phosphate backbone of RNA to form the atypical spatial form, which is recognized by translational factors [43]. The critical bases A2660, G2661, and A2662 in the GAGA loop (*E. coli* numbering) associate with each other via non-canonical π-stacking interactions that stabilize the loop structure [42,43]. The crucial A2660, located at the top of the hairpin structure, is stabilized via the stacking interactions with G2661 (Figure 2B). Importantly, A2660 is fully exposed and does not form any hydrogen bonds with other bases of the loop, making it easily accessible to external factors like ricin [49]. Biochemical studies on prokaryotic and eukaryotic ribosomes have shown that the SRL represents a critical element responsible for the interaction and stimulation of all trGTPases activity [50,51]. Additionally, it has been early recognized that this structure represents the main target for numerous toxins [50,52–54]. Recent structural analyses have brought detailed insight into the intricate interplay between the SRL and trGTPases and at the same time cast light on the molecular aspects of ricin toxicity [28,29,40,55]. In general, all trGTPases interact with the SRL via the GTP-binding domain (G-domain) comprising the active site of the factor, responsible for GTP hydrolysis [17]. It should be stressed that the structure of the G-domain is evolutionarily conserved among all trGTPases, and biochemical and structural investigations support the notion that the mechanism of activation of GTP hydrolysis by the ribosome is universally conserved [17,56]. The trGTPases convert chemical energy into mechanical forces at the expense of GTP hydrolysis, and this drives the ribosome through the translational cycle. The key role in catalysis is played by an invariant histidine residue (His84 in EF-Tu, His87 in EF-G, or His61 in SelB, or His108 in eEF2) [56–60]. This histidine may adopt two conformations: an inactive "flipped-out" state (pointing away from the γ-phosphate of GTP) and an active flipped-in state (reaching towards the γ -phosphate) (Figure 3). After joining the factor to the ribosome, the SRL is "inserted" into the catalytic center of the G-domain, and the phosphate moiety of A2662 coordinates, by means of electrostatic interactions, the catalytic histidine positioning to the active "flipped-in" position towards the γ-phosphate of GTP [28,38,61]. The positively charged histidine points towards the water molecule aimed at the nucleophilic attack on GTP γ-phosphate [29,38,58,62]. Additionally, the phosphate of A2662 coordinates a Mg2+ ion, important in positioning of the Asp residue (Asp21 in EF-Tu, Asp22 in EF-G, Asp10 in SelB), which is also crucial for GTP hydrolysis (Figure 3) [28,58].

**Figure 3.** Model of GTP hydrolysis activation with the aid of sarcin–ricin loop (SRL), with the EF-G as trGTPase. Left panel: the organization of the active site in isolated EF-G. Asp22 and His87 are in "flipped-out" state, pointing away from GTP; the "hydrophobic gate" formed by amino acids Ile63 and Ile21 prevents His87 from adopting the active conformation. Right panel: the reorganization of the active site of EF-G as a result of binding of EF-G to ribosome and inserting the SRL to the G-domain. Base A2660 interacts with His20, which induces Ile21 movement away from GTP and "hydrophobic gate" opening. The phosphate of A2662 directs His87 and Asp22 residues (through Mg2+) to "flipped-in" conformation which allows for water molecule activation and GTP hydrolysis (see the details in the text).

Recently, A2662 and G2661 within the tetraloop structure were distinguished as critical elements, directly involved in stimulation of the GTP hydrolysis process [28,38]. Interestingly, α-sarcin cleaves the bond between eukaryotic nucleotide equivalents to *E. coli* G2661 and A2662, which results in ribosome inactivation [63,64]. The A2660 base, which is cleaved-off by ricin, plays a distinct but weighty function, which could be named as the "power behind the throne" title role. As shown based on the structure of the EF-G–ribosome complex in a pre-translocation state, an intricate network of hydrogen-based interactions involving the G2661 and A2660 of the SRL, EF-G (Glu456, Arg660, Ser661 and Gln664), and ribosomal L6 (Lys175) is formed in the immediate vicinity of the GTPase active site, with A2660 being the central element of the network [40]. Thus, depurination of A2660 may prevent the surrounding elements from adopting the active conformation, which is required to bind the metal ions necessary to stabilize Asp22 and neighboring regions of EF-G in the activated form [55,65]. On the other hand, A2660, together with G2661, plays a crucial role in opening of a so-called hydrophobic gate, which prevents the invariant His residue in the free trGTPase from achieving an active state and spontaneous GTP hydrolysis. In the complex of the EF-G/ribosome, the bases A2660 and G2661 interact with His20 of EF-G, which in turn interacts with Ile21, forming a hydrophobic gate with Ile63. These interactions contribute to its opening and repositioning the His87 into its active position [40]. The structural analyses of the A2660 role are supported by biochemical insight. It has been shown that lack of the single exocyclic N6 amino group at position 2660 within rRNA inhibited GTP hydrolysis on the EF-G/ribosome complex. Importantly, the introduction of different exocyclic groups with dissimilar chemical groups, such as inosine, dimethyladenosine, or even 6-methylpurine, restored

the GTP hydrolysis activity of EF-G. The experimental biochemical data indicate that the critical favorable chemical feature is related to electron configuration that allows participation in the aromatic π-electron interaction system of the purine, which in turn facilitates the π-stacking e ffect [66]. It should be underlined that despite the vast number of data collected from only the bacterial model, the amino acid sequence, called PGH motif (with the invariant His residue) is universally conserved and present in EF-Tu, EF-G, IF2, and RF3, as well as archeal and eukaryotic trGTPases [67]. What is more, the highly conserved A2660 base moiety (A3027 - yeast, A4324 - rat, A4605 - human) within the tetra-loop of SRL [56] represents the most crucial base which contributes to a cooperative interaction network, which stabilizes the active state of trGTPases, promoting GTP hydrolysis.


**Acknowledgements**

This work was funded by the Italian Ministry of Agriculture, Food, and Forestry Policies (MiPAAF), within the trans-national project INTIMIC–Knowledge Platform on food, diet, intestinal microbiomics, and human health of the Joint Programming Initiative Healthy Diet for a Healthy Life (JPI-HDHL), Expression of Interest n. 795 (MICROFLUX Project, MiPAAF DM 36954/7303/18).


**1. Introduction**

In this paper we propose the design and construction of a modular robot composed by several links which are reconfigurable in shape and size in order to generate different adaptable configurations of the robotic platform. The primary characteristics for this design are the scalability and modularity of the robot. Two designs will be proposed:

A Modular Robotic System (MRS) can be defined as link arrays joined together to form a modular structure [3]. MRSs have four interdependent components: Module, Information, Task, and Environment (MITE). MITE allows for the extraction of the characteristics of the MRS, the module properties being the most special features, as other MRS components are transversal to every kind of robot. The module component includes two useful properties for the design of an MRS, these are: class and architecture. The class refers to the different ways in which modularity can be achieved, such as fixed-configuration, manually-reconfigurable [2,4], self-reconfigurable [5,6], and self-replicable [7]. On the other hand, architecture is the hardware categories of configuration: Chain [4,5], Lattice [6,8,9], Mobile [10–12], Hybrid [13,14], Truss [15–17], and Free form [18,19].

Many MRSs change their shape and size through nesting between each module; however, in this case study our goal is to allow the resizing of each module before its connection. This configuration is not often used in the literature. For instance, the closest example is ShapeBots, which is an individual shape-changing link [20] but with no modularity capabilities. A reference work closer to our approach is the Extendable Arm by Matsuo et al. [21], where modular links are connected and each one is scalable. Compared to our approach, the orientation of this platform is limited and its operation is manual. Thanks to the introduction of a three degrees of freedom (DoF) joint connecting each link, our design allows a wider orientation range of the modular robot. Besides, the platform performs automatically thanks to the use of a control system, which avoids the manual operation of the robot and improves its usability.

**Citation:** Mena, L.; Muñoz, J.; Monje, C.A.; Balaguer, C. Modular and Self-Scalable Origami Robot: A First Approach. *Mathematics* **2021**, *9*, 1324. https://doi.org/10.3390/math9121324

Academic Editors: Mikhail Posypkin, Vladimir Titarev and Andrey Gorshenin

Received: 30 April 2021 Accepted: 1 June 2021 Published: 9 June 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 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/).

The initial idea about a flexible structure deforming by sections led us to origami-type constructions. Origami is an ancient technique for paper folding [22], which provides deployable structures that can be reconfigured and change in size and shape. Reconfigurable 3D structures, obtained from a rigid geometric 2D pattern, are booming in designs for engineering applications such as the solar panel surfaces proposed by Miura [23], the modular origami continuous manipulator by Santoso et al. [24], which supports a 1 kg mass at its tip, a gripper with multiple grasp modes [25], and other applications such as biomechanical [26], space [27], or soft robotics [28]. The wide number and type of applications of these designs has motivated us to research this topic and present a different approach in the terms described next.

Our design proposal consists of a modular robot that uses an origami-inspired linkbased resizing mechanism. The links can be assembled using a rigid connector or a 3 DoF joint as proposed below. In this study we use the Kresling pattern for the origami structure of the basic link. This pattern is formed by the folding of a thin-walled cylinder when subject to twist buckling under a torsional load. It is characterized by alternating mountain and valley folds angled along the direction of the twist [29,30].

Figure 1a represents an *n* faces polygon Kresling pattern in planar state, which forms a polyhedral cylinder when assembled. The triangulated polyhedron geometry is resolved by *LAB* = *a*, *LBC* = *a* · *sin*(*α*)/*sin*(*β*), *LAC* = *a* · *sin*(*α* + *β*)/*sinβ* at the planar state, where *a*, *α*, and *β* are constant values. The angles *α* and *β* are the main design criteria to create the cylinder, because the strength of the structure depends on them. Zhai et al. suggest that, for small angles around 30◦, the structure is easy to deploy and easy to collapse, and for greater angles around 50◦, the structure is hard to deploy and hard to collapse [31]. For large angles, the structure is stronger and able to support loads. To obtain a symmetric structure we consider *a* = *r* = 30 mm; therefore, *n* = 2*π* according to Hunt [32], where *a* = 2*πr*/*n* and *β* = *π*/*n*. The angle *α* has been obtained from the geometric resolution proposed by Jianguo et al. [33]. Here *h* is considered to be known, *α* = *asin*(*d*/*a*) and *d* can be obtained by *ah* = *d*(*d* · *cot*(*β*) + √*a*2 − *d*2). Consequently, our prototype has been designed with *a* = 30 mm, *h* = 34.25 mm, *β* = 30◦ and *α* = 38◦, thus a flexible deformable link is created, and the unitary ABC triangle angle is >90◦ to achieve continuous strain at each member tension or compression in the deployed and collapsed states.

The folded cylinder link state generates a twist angle *θ* with radius *r* while height *h* is compressed (Figure 1b). This bistable behavior is due to the change of the lines length during folding (Equation (1)).

$$\begin{aligned} l\_{AB} &= 2r \sin(\pi/n) \\ l\_{BC} &= \sqrt{h^2 - 2r^2 \cos \theta + 2r^2} \\ l\_{AC} &= \sqrt{h^2 - 2r^2 \cos(2\pi/n + \theta) + 2r^2} \end{aligned} \tag{1}$$

$$r = \frac{\frac{q}{2}}{\sin\left(\frac{\pi}{n}\right)}\tag{2}$$

$$\theta = \frac{2\pi}{n} - 2a\sin\left(\frac{l\_{\rm BC}\cos\delta}{2r}\right) \tag{3}$$

$$h = l\_{BC} \cdot \sin(\delta) \tag{4}$$

The height value *h* changes during folding and this change is related to *δ* angle change, given by Equation (4), as illustrated in Figure 1c. The variable height and bistability allow the self-scaling of the simple link.

**Figure 1.** Origamipolyhedron Kresling pattern. (**a**) 2D Kresling pattern. (**b**) Folded cylinder link state. (**c**) Biestable behavior.

The main contributions of this work with respect to the state of the art are the following:


**4.1 ACR recommendations for reproductive health-care in SLE**

In 2020, *American College of Rheumatology* (ACR) releases an updated guideline with recommendations for reproductive health-care in rheumatic diseases, particularly SLE with and without anti-Ro/La and aPL antibodies [6].

Hereby we summarized the most important statements regarding pregnancy counseling, assessment and monitoring to improve maternal and fetal outcomes in SLE women (**Figure 1**) [6]**:**

#### **Figure 1.**

*Pregnancy counseling, assessment and management in woman with SLE (ACR2020 adapted) [6]. \*If on; \*\*if not a contraindication; NLE, neonatal lupus; HB, heart block; CBH, complete heart block.*

persistence of unchanged titers of these antibodies, ACR strongly recommend *against* repeating the test during pregnancy. Besides, it is also strongly recommend testing for aPL before or early in pregnancy, while repeating these tests during pregnancy is not necessary [6];


**2. The role of inflammation in functional dyspepsia**

Inflammation has the potential to contribute to the development of FGIDs via the release of specific mediators that impact mechanisms known to play a role in the pathogenesis of these conditions. Acute gastrointestinal inflammation and injury are associated with both peripheral

**Figure 1.** The Biopsychosocial Model of FD

meal. The second subtype, epigastric pain syndrome, was defined as intermittent pain or burning localized to the epigastrium (i.e., not generalized or localized to other abdominal or chest regions) and of at least moderate severity. The Rome III pediatric subcommittee also eliminated the old subtypes, but did not adopt the new adult subtypes because of a lack of existing data to support their existence in children and adolescents. However, recent evidence suggests that the adult subtypes actually may have meaningful associations with mucosal

Most pediatric gastroenterologists may not routinely use Rome criteria and differences exist in how the criteria are interpreted. Nevertheless, there is agreement that a strong majority of children with chronic abdominal pain presenting to pediatric gastroenterology practices fulfill criteria for an FGID, with the two most common being FD and IBS [6-9]. Community preva‐ lence for FD is estimated at 3.5-27% in children/adolescents compared to 20-30% in adults [3,4]. In both pediatric and adult gastroenterology practices, FD frequently overlaps with IBS or gastroesophageal reflux [7,10]. Adult IBS overlap is associated with more psychological dysfunction including anxiety and depression, compared to "pure" FD, but this association does not appear to be present in pediatric overlap [11,12]. Pediatric FD is associated with lower quality of life, increased functional disability, and increased likelihood of meeting criteria for an anxiety disorder relative to healthy children [13]. In adults with FD, the association with anxiety appears to be specific to patients with postprandial distress syndrome, with this relationship also apparent in children/adolescents with symptoms consistent with postpran‐

FD, like all FGIDs, is probably best understood through a biopsychosocial model (see Figure 1). This model states that symptoms are likely the result of varying contributions from, and interactions between, biological/physiological factors (e.g. inflammation, mechanical distur‐ bances, hypersensitivity), psychological factors (e.g. anxiety, depression, somatization), and social factors (e.g. interactions with parents, teachers, or peers). Within this model, there is less emphasis on the "cause" of symptoms than on "contributors" to its emergence and mainte‐ nance. This model would suggest that there is value in identifying and targeting all of the factors which might be contributing to symptom generation in children with FD. It also would suggest that there is value in understanding the mechanisms by which the factors interact with one another, as these mechanisms represent additional opportunities for clinical intervention.

Inflammation has the potential to contribute to the development of FGIDs via the release of specific mediators that impact mechanisms known to play a role in the pathogenesis of these conditions. Acute gastrointestinal inflammation and injury are associated with both peripheral

**2. The role of inflammation in functional dyspepsia**

inflammation and psychosocial functioning in pediatric FD [5].

**1.2. Prevalence and presentation**

30 Dyspepsia - Advances in Understanding and Management

dial distress syndrome [5,14].

**1.3. Etiology**

and central sensitization of the nervous system, which results in visceral hyperalgesia [15]. Neuroplastic changes may occur that affect the response thresholds of enteric nerves, thereby negatively impacting both sensitivity and motility [16]. Both motility and sensitivity responses to acute inflammation in adults generally are reversible; however, animal model responses suggest that, if inflammation occurs in neonates, neuroplastic changes and sensitivity may persist into adulthood [17,18]. Visceral sensitization may be even more relevant in instances where there is chronic inflammation with ongoing mediator release, as there may be subse‐ quent effects on visceral sensitivity that compound and prolong the issue.

The role of inflammation in FD has historically been controversial. However, emerging evidence supports its role as a contributing factor in the biopsychosocial model of FD. In fact, inflammation may be of particular importance in this model, as it interacts with a number of other factors and may actually mediate the relationship between psychologic and physiologic factors. The remainder of this chapter focuses on examination of inflammation within the biopsychosocial model of FD, laying out the current evidence for its prevalence, mechanisms of action, relationship with other important factors, and implications for evaluation and treatment.

**2.3. Eosinophils**

≤20/hpf in the duodenum in 93% [31].

Ethical considerations preclude undertaking studies that assess eosinophil density in healthy pediatric controls. However, the available pediatric literature indicates that it is reasonable to consider eosinophil densities ≥10/hpf in the antrum and >20/hpf in the duodenum to be abnormal. In a pediatric autopsy study, eosinophil density was <10/hpf in the antrum of all subjects and ≤20/hpf in the duodenum of 82%, even though symptoms could not be docu‐ mented [30]. Another study reviewed biopsies from 682 presumably symptomatic children referred for endoscopy, documenting eosinophil density ≤10/hpf in the antrum in 90% and

Inflammation and the Biopsychosocial Model in Pediatric Dyspepsia

http://dx.doi.org/10.5772/56635

33

While certain cut-off points for density seem reasonable, eosinophil density may not be completely informative. Eosinophil biologic activity occurs through mediator release or degranulation, and the effects are generally concentration-dependent. Important to consider is the fact that density and activation are not correlated events [32]. In one study involving 20 children with FD, eosinophil density >20/hpf was present in only 15%; however, moderate to

Adult population studies have demonstrated increased duodenal eosinophil density in those with dyspepsia compared to controls, whereas antral eosinophils did not differ between the groups [34,35]. Higher eosinophil density and a higher prevalence of duodenal eosinophilia (as defined by application of the cut points outlined above) have been specifically associated with the postprandial distress syndrome subtype of FD in adults [36]. Duodenal biopsies from adults with FD also have revealed more extensive degranulation, including documentation of extracellular major basic protein; this corresponds to a similar finding of degranulation and release of major basic protein previously demonstrated in pediatric patients with FD [33,35].

Although no information is available for healthy children, tissue eosinophilia has been evaluated in the broad group of children with chronic abdominal pain, which provides some limited basis for comparison. In a study of 1191 children with chronic abdominal pain, eosinophilia was identified in the antrum or duodenum in 11.4% [37]. In another study, gastric eosinophilia was reported in 19% and duodenal eosinophilia in 32% of children with unspe‐ cified chronic abdominal pain [19]. In contrast, duodenal eosinophilia has been demonstrated

Antral eosinophil density does not appear to have any direct relationship to gastric electro‐ mechanical function in children with FD [28]. However, in patients with elevated mucosal eosinophils, antral CD3+ cell density does correlate with preprandial tachygastria, indicating

There are a number of triggers or inciting events which may initiate an inflammatory response in the gastrointestinal tract, particularly with regard to recruitment and activation of mast cells

extensive degranulation was demonstrated by electron microscopy in 95% [33].

in 79% of children specifically fulfilling FD criteria [38].

that it may result from the interaction between different cell types [28].

**3. Specific Conditions Associated with Mucosal Inflammation**

#### **2.1. Chronic inflammation**

Upper endoscopy is commonly performed in children with chronic abdominal pain in general and children with functional dyspepsia in particular. Histologic inflammation is common in these patients. In children with chronic abdominal pain, esophagitis is common and would implicate gastroesophageal reflux as a contributor or cause of pain [19]. In one study of children with FD, specifically, histologic esophagitis was found in 18%, gastritis in 21%, and duodenitis in 13% [10]. Higher prevalences for gastritis, ranging from 43% to 71%, have been reported by others [20,21]. For the broader group of children with chronic abdominal pain, histologic inflammation has been documented in up to 79%, with an increase in mononuclear cells (indicative of chronic inflammation) in the antrum of 55% and in the duodenum of 16% of these children [19].

Most of these patients have chronic inflammation of which the clinical significance is unknown. Chronic gastritis is not associated with electrogastrographic abnormalities, delayed gastric emptying, or psychologic dysfunction in children with FD [5,22]. Despite this, chronic active gastritis (manifest as lymphocytic and neutrophilic inflammation) has been associated with a higher prevalence of nocturnal pain [21]. Chronic gastritis has been associated with an increased prevalence of postprandial pain [5].

#### **2.2. Mast cells**

Increased mucosal mast cell density has been demonstrated in the gastric corpus and antrum in adults with FD [23,24]. In adults with gastritis, mast cell density is significantly increased and generally correlates with the intensity of the inflammation [25]. Though findings have been variable, increased mast cell density appears isolated to the stomach in adults with FD; increased duodenal mast cell density is more associated with IBS [24,26]. In addition, increased mast cells in the proximal stomach in adults with FD have been associated with hypersensi‐ tivity; these mast cells will degranulate with balloon distension of the proximal stomach [27].

Due to a lack of normal control data, it is not known if gastric mast cells are elevated in pediatric FD. However, antral mast cells do appear to be actively degranulating in children with FD, with a mean degranulation index of 67% and greater than 50% degranulation in over 80% of patients [28]. In children with FD, mast cell density positively correlates with slower gastric emptying and increased gastric dysrhythmia (primarily preprandial bradycardia) in children with FD [28]. Further, this dysrhythmia is associated with increased postprandial pain [29].

#### **2.3. Eosinophils**

The role of inflammation in FD has historically been controversial. However, emerging evidence supports its role as a contributing factor in the biopsychosocial model of FD. In fact, inflammation may be of particular importance in this model, as it interacts with a number of other factors and may actually mediate the relationship between psychologic and physiologic factors. The remainder of this chapter focuses on examination of inflammation within the biopsychosocial model of FD, laying out the current evidence for its prevalence, mechanisms of action, relationship with other important factors, and implications for evaluation and

Upper endoscopy is commonly performed in children with chronic abdominal pain in general and children with functional dyspepsia in particular. Histologic inflammation is common in these patients. In children with chronic abdominal pain, esophagitis is common and would implicate gastroesophageal reflux as a contributor or cause of pain [19]. In one study of children with FD, specifically, histologic esophagitis was found in 18%, gastritis in 21%, and duodenitis in 13% [10]. Higher prevalences for gastritis, ranging from 43% to 71%, have been reported by others [20,21]. For the broader group of children with chronic abdominal pain, histologic inflammation has been documented in up to 79%, with an increase in mononuclear cells (indicative of chronic inflammation) in the antrum of 55% and in the duodenum of 16% of

Most of these patients have chronic inflammation of which the clinical significance is unknown. Chronic gastritis is not associated with electrogastrographic abnormalities, delayed gastric emptying, or psychologic dysfunction in children with FD [5,22]. Despite this, chronic active gastritis (manifest as lymphocytic and neutrophilic inflammation) has been associated with a higher prevalence of nocturnal pain [21]. Chronic gastritis has been associated with an

Increased mucosal mast cell density has been demonstrated in the gastric corpus and antrum in adults with FD [23,24]. In adults with gastritis, mast cell density is significantly increased and generally correlates with the intensity of the inflammation [25]. Though findings have been variable, increased mast cell density appears isolated to the stomach in adults with FD; increased duodenal mast cell density is more associated with IBS [24,26]. In addition, increased mast cells in the proximal stomach in adults with FD have been associated with hypersensi‐ tivity; these mast cells will degranulate with balloon distension of the proximal stomach [27].

Due to a lack of normal control data, it is not known if gastric mast cells are elevated in pediatric FD. However, antral mast cells do appear to be actively degranulating in children with FD, with a mean degranulation index of 67% and greater than 50% degranulation in over 80% of patients [28]. In children with FD, mast cell density positively correlates with slower gastric emptying and increased gastric dysrhythmia (primarily preprandial bradycardia) in children with FD [28]. Further, this dysrhythmia is associated with increased postprandial pain [29].

treatment.

**2.1. Chronic inflammation**

32 Dyspepsia - Advances in Understanding and Management

these children [19].

**2.2. Mast cells**

increased prevalence of postprandial pain [5].

Ethical considerations preclude undertaking studies that assess eosinophil density in healthy pediatric controls. However, the available pediatric literature indicates that it is reasonable to consider eosinophil densities ≥10/hpf in the antrum and >20/hpf in the duodenum to be abnormal. In a pediatric autopsy study, eosinophil density was <10/hpf in the antrum of all subjects and ≤20/hpf in the duodenum of 82%, even though symptoms could not be docu‐ mented [30]. Another study reviewed biopsies from 682 presumably symptomatic children referred for endoscopy, documenting eosinophil density ≤10/hpf in the antrum in 90% and ≤20/hpf in the duodenum in 93% [31].

While certain cut-off points for density seem reasonable, eosinophil density may not be completely informative. Eosinophil biologic activity occurs through mediator release or degranulation, and the effects are generally concentration-dependent. Important to consider is the fact that density and activation are not correlated events [32]. In one study involving 20 children with FD, eosinophil density >20/hpf was present in only 15%; however, moderate to extensive degranulation was demonstrated by electron microscopy in 95% [33].

Adult population studies have demonstrated increased duodenal eosinophil density in those with dyspepsia compared to controls, whereas antral eosinophils did not differ between the groups [34,35]. Higher eosinophil density and a higher prevalence of duodenal eosinophilia (as defined by application of the cut points outlined above) have been specifically associated with the postprandial distress syndrome subtype of FD in adults [36]. Duodenal biopsies from adults with FD also have revealed more extensive degranulation, including documentation of extracellular major basic protein; this corresponds to a similar finding of degranulation and release of major basic protein previously demonstrated in pediatric patients with FD [33,35].

Although no information is available for healthy children, tissue eosinophilia has been evaluated in the broad group of children with chronic abdominal pain, which provides some limited basis for comparison. In a study of 1191 children with chronic abdominal pain, eosinophilia was identified in the antrum or duodenum in 11.4% [37]. In another study, gastric eosinophilia was reported in 19% and duodenal eosinophilia in 32% of children with unspe‐ cified chronic abdominal pain [19]. In contrast, duodenal eosinophilia has been demonstrated in 79% of children specifically fulfilling FD criteria [38].

Antral eosinophil density does not appear to have any direct relationship to gastric electro‐ mechanical function in children with FD [28]. However, in patients with elevated mucosal eosinophils, antral CD3+ cell density does correlate with preprandial tachygastria, indicating that it may result from the interaction between different cell types [28].


**Acknowledgments:** The authors thank Umberto Mercurio and Guido Saccone at CIRA for their support in interacting with the industrial experts and collecting their inputs.

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

#### **References**

MDPI St. Alban-Anlage 66 4052 Basel Switzerland Tel. +41 61 683 77 34 Fax +41 61 302 89 18 www.mdpi.com

*Aerospace* Editorial Office E-mail<EMAIL_ADDRESS>www.mdpi.com/journal/aerospace

MDPI St. Alban-Anlage 66 4052 Basel Switzerland Tel: +41 61 683 77 34

www.mdpi.com ISBN 978-3-0365-6347-3


**5. Method**

during the 1990s also increased the possibility of including personal photos in AAC systems, which, according to clinical reports, seemed to increase motivation and facilitate understand‐

There are, however, also reports of problems in teaching symbols to children with ASD, mainly in teaching them to use the pictures spontaneously and for communicative functions other than requesting [41]. It was precisely these problems that led Bondy and Frost [47] to develop the method called Picture Exchange Communication System (PECS). PECS is a systematic approach to communication training specifically developed for children with autism. The elements that make PECS different from other visual-graphic techniques are the use of the concrete hand-to-hand exchange of the picture and also the highly prescriptive user manual

Historically, the use of speech output technologies with individuals with ASD has not been a matter of course [48]. Computer technology was introduced into educational settings for children with autism late, not only in North America, but also in other countries.  Concerning speech-generating devices (SGDs), a common view was that they would only stimulate echolalia in children with ASD, and that there would be too much noise in the classroom. By the end of the 1990s, scepticism had decreased. This was probably due to reports of some studies of successful computer-assisted instruction (CAI) carried out. The introduction of "app technology "has meant a revolution to the field of speechgenerating devices and the first studies of the effects of apps are now being published.

The term evidence-based used as a prefix and a denominator of interventions and methods comes from medicine. The term evidence based means that the choices of interventions and as‐ sessments are based on a research literature not simply professional experience or previous practice. Evidence-based practice has been important within the area of early communication intervention. The behavioural intervention tradition with its roots in the research clinic has pro‐ duced a lot of high-quality research during the years. Other types of interventions has been less researched and sometimes have used methods and produced data that are different so that com‐ parisons of effects are hard or impossible to do. This has also led to an interesting discussion of how to do EPB within the field of communication intervention. Ralph W. Schlosser, professor at NorthEastern University, USA, has been of great importance in this respect. Partly because he is spreading knowledge about evidence-based practise (EBP) and due to the many thorough com‐ pilations of research that he has done, but also in demonstrating the problems and shortcom‐ ings using EBP in relation to the field of augmentative communication intervention [49]. One of these problems concerns the use of the Randomized Controlled Trial or Study (RCT) as the gold‐ en standard, as RCTs are almost non-existent within the AAC field. There are many reasons to this but the main ones are that (1) children with communicative disabilities are so heterogene‐ ous and (2) that randomization is extremely difficult to put through due to ethical reasons.

ing of pictures, particularly for individuals with ASD [46].

with its six levels to follow in sequence.

726 Recent Advances in Autism Spectrum Disorders - Volume I

**4. Evidence-Based Practice — EBP**

#### **5.1. EBP-group**

The review of research within the field of early communication intervention that is presented in this study was initiated by the Swedish association of Habilitation directors as part of a project concerning EBP that was started 2002. Within the frames of this project several reports have been produced with respect to interventions for children and adults with disability. The author of this chapter was appointed scientific leader for a group of five speech-language pathologists and one special educator in Sweden, that applied for taking part in the project. The group has worked together during recurrent two-day-sessions and in between, work has also been done separately and in pairs.

#### **5.2. EBP-method and search question**

The group decided to use the EBP-model of Ralph Schlosser [49]. As mentioned above the hier‐ archy of evidence of Schlosser is a bit different compared to the traditional ones, in that it places the meta-analysis on top of the hierarchy beside the RCT-study. Schlosser also includes per‐ spectives of the stakeholder and the influence of environment into his model of EBP and defines EBP as follows: "The integration of best and current research evidence with clinical/educational expertise and relevant stakeholder perspectives to facilitate decisions for assessment and inter‐ vention that are deemed effective and efficient for a given stakeholder". The classical model of formulation of a evidence question shortened PICO - Problem, Intervention, Comparison, Out‐ come - has accordingly been revised into PESICO - Problem, Environment, Stakeholders, Inter‐ vention, Comparison, Outcome [49]. The question that was formulated in this review was: A young child with severe communicative disability, living with his/her parents and being placed in a pree-school group: which intervention is most effective; indirect or direct interventions.

#### **5.3. Procedure**

When the clinical question had been formulated the group identified search terms to use. These were: Early Intervention, Communication, Communication Disability/ies, Direct intervention, Indirect intervention, Early childhood, Kindergarten, Pree-school, AAC, Augmentative Com‐ munication, Alternative Communication, Early Communication, Language, Meta-analysis, Review. The terms were searched separately and in combinations using four scientific data bas‐ es: PubMed, PsycInfo, CINAHL and ERIC. It was seen that CINAHL generated significantly more results than the other three. All abstract were browsed and the studies considered as rele‐ vant were downloaded. The reference lists of these studies led to some new findings. A few studies and book chapters were found through the group's different contacts and readings of literature. The studies were read and reviewed using a protocol and a manual that was devel‐ oped. The factors that were examined in each study were: Research methods, participants, envi‐ ronment, intervention, results, evidence grading and a final category called notes. This column included judgements of (a) ICF domain/s that the study involved, (b) validity: internal, external, social and ecological, (c) importance of discussion and suggestions of future studies.

**Author&year Study design Intervention Evidence grading**

the use of responsive strategies

Early Communication Intervention for Children with Autism Spectrum Disorders

ComAlong parental education; responsive strategies and AAC

Pilot RCT Focus parent training; joint attention Schlosser: 1

imitation and responsive strategies

Hanen More than Words parental education and guidance: responsive

(and also some older children)

ComAlong parental education; responsive strategies and AAC

ComAlong parental education; responsive strategies and AAC

ComAlong parental education; responsive strategies and AAC

Hanen More than Words parental education and guidance: responsive

fathers as analyzed by video

including responsive strategies

Parents and course leaders' experiences of the ComAlong augmentative and alternative communication early

Large-scale SSRD Education and guidance of fathers:

intervention course

strategies

strategies

Group study Verbal outcomes after training of

interactions

Group study Evaluation of the parental plus progam

Oosterling et al., 2010 [63] RCT Focus parent training; joint attention Schlosser: 1

RCT PECS – training of pree-school teachers

Schlosser: 1 Nordenström Golper. III

http://dx.doi.org/10.5772/54881

729

Schlosser: 5 Nordenström: B Golper. II

Nordenström: A Golper. III

Schlosser: 2 Nordenström: B Golper. III

Schlosser: 5 Nordenström: B Golper. II

Schlosser: 5 Nordenström: C Golper. III

Schlosser: 1 Nordenström: A Golper. III

Schlosser: 5 Nordenström: B Golper. II

Schlosser: 5 Nordenström: B Golper. I

Schlosser: 5 Nordenström: B Golper. II

Schlosser: 2 Nordenström: B Golper: III

Nordenström: A Golper. III

Schlosser: 2 Nordenström: B Golper. III

Schlosser: 5 Nordenström: B Golper. II

Aldred, Green & Adams, 2004 [54] RCT Education and guidance of parents in

Group study; mixed methods

Case study, Interaction analyses

Pre-experimental group study; mixed methods

mixed methods

control group

study

**Table 2.** Studies of education and guidance to parents or staff

Controlled group

group-study

Callenberg och Ganebratt, 2009 [56] Pre-experimental

Drew, Baird, Baron-Cohen, Cox, Slonims, Wheelwright, Swettenham, Berry & Charman, 2002 [32]

2005 [57]

2007 [58]

Thunberg, 2011 [55]

Charman, 2007 [59]

Elder, Valcante, Yarandi, White & Elder,

Ferm, Andersson, Broberg, Liljegren &

Girolametto, Sussman & Weitzmann,

Howlin, Gordon, Pascoe, Wade &

Jonsson, Kristoffersson, Ferm & Thunberg, 2011 [40]

McConachie, Randle, Hammal & LeCouteur, 2005 [61]

Seung, Ashwell, Elder & Valcante, 2006

Sharry, Guerin, Griffin & Drumm, 2005

[64]

[65]

Karlsson & Melltorp, 2006 [62] Pilot group study,

Lennartsson och Sörensson, 2010 [60] Group study, small

Each study was first reviewed by two group members separately and then discussed and graded by the group altogether. The group graded the studies according to three systems: Schlosser [49], Nordenström [51] and Golper [52]. Schlosser's system was seen as the most important for this study due to the fact that it was developed for the field of communication intervention for people with disability. Nordenström represent the classical medical evidence hierarchy whilst the Golper was included for its ambition to catch or grade the level or depth of evaluation that the study represents.

**Table 1.** Systems for evidence-grading being used in this study. SSRD=Singel Subject Research Design, RCT=Randomized Controlled Study

**Table 2.** Studies of education and guidance to parents or staff

studies and book chapters were found through the group's different contacts and readings of literature. The studies were read and reviewed using a protocol and a manual that was devel‐ oped. The factors that were examined in each study were: Research methods, participants, envi‐ ronment, intervention, results, evidence grading and a final category called notes. This column included judgements of (a) ICF domain/s that the study involved, (b) validity: internal, external,

Each study was first reviewed by two group members separately and then discussed and graded by the group altogether. The group graded the studies according to three systems: Schlosser [49], Nordenström [51] and Golper [52]. Schlosser's system was seen as the most important for this study due to the fact that it was developed for the field of communication intervention for people with disability. Nordenström represent the classical medical evidence hierarchy whilst the Golper was included for its ambition to catch or grade the level or depth

social and ecological, (c) importance of discussion and suggestions of future studies.

2 Well designed non-RCT group study SSRD – one intervention SSRD – several interventions

Subgroups to/variants of the types above 3 Narrative quantitative reviews (except of meta-analyses)

6 Expertise: educational books, journals, expert opinion

studies, case studies, cohort studies)

Golper Phase I Hypotheses about treatment efficacy are being developed for later testing.

or activity of a particular treatment.

Phase II The goals are to formulate and standardize protocols, validate

Nordenström A Strong scientific evidence (meta-analysis, well-done and large RCT)

descriptive reports)

treatment comparisons.

comparisons.

**Table 1.** Systems for evidence-grading being used in this study. SSRD=Singel Subject Research Design,

5 Pre- experimental group studies (i.e. before-after) and case studies

B Moderate evidence (smaller or non-randomized studies, cross-sectional

C Week evidence (expert opinion, concensus reports, case studies and other

Often this involves experimental manipulations to test potential benefits

measurement instruments, optimise dosage of treatment, and so on. Includes case reports and small group studies with no control groups or

SSRD or group studies with controls such as control groups or treatment

D Non-existent scientific evidence (No studies of sufficient quality exists).

Phase III Treatment efficacy of a specified protocol is formally tested either with

of evaluation that the study represents.

728 Recent Advances in Autism Spectrum Disorders - Volume I

RCT=Randomized Controlled Study

**System Level Definition**

Schlosser 1 Meta-analyses of SSRD /RCT

4 Narrative reviews

The results were analysed and grouped primarily according to the formulated search question but also according to the identified areas of intervention and methods being evaluated in the studies. Building on these results, recommendations and a model for early communicative intervention was suggested. These results were documented in a report being published on the website of the Association of Swedish Habilitation directors [53]. A new literature search using the same procedure as described above led to some revision of results and recommen‐ dations in a new version of the report that was recently published [53].

guidance of parents (for example 31, 63, 74, 75, 81). Several of these interventions includ‐ ed education that was combined with home-visits when the therapist interacted with and trained the child during natural play situations. The parents observed these play activi‐ ties and the therapist's use of behavioural strategies, which were then discussed an prac‐ ticed during the sessions. The results of these comprehensive programs are included in the section of direct interventions below (table 3), but it is important to also recognize

Early Communication Intervention for Children with Autism Spectrum Disorders

http://dx.doi.org/10.5772/54881

731

In several studies of the interventions more specifically aimed at parental education, it was seen that the parent's use of responsive strategies increased [54, 58, 60, 61, 62] and some studies showed that interaction between the parent and the child was positively af‐ fected [57, 58, 62, 65]. Some studies report that the development of communication and language in the child seems to be increased when the parents are provided with educa‐ tion and guidance [32, 54, 56, 61, 62, 64]. Several studies have tried to measure parental stress and other family related parameters that are expected to be affected, also out from parental interviews [54, 55, 56, 61, 65]. Most studies failed in proving effects in this re‐ spect, at least on a level of statistical significance. In some studies the researchers specu‐ late that the questionnaires given before and after an intervention seems to fail in catching an effect. In qualitative studies parents report that they can see the problems of the child more clearly after the course and can be more open about the family problems [55]. This means that items related to family issues even might "get worse" comparing

So far very little is known of the long-term effects of indirect intervention. The few studies with this focus show that the effects seem to fade over time. Both clinicians and researchers hypothesize that there probably is a need to do follow-ups and/or provide booster interven‐ tions to maintain the intervention effects over time. There are also indications that the effects of a parental education on the development of the child seems to be further enhanced when

19 studies were found of which 10 were reviews (1 meta-analysis) and the rest primary studies. The scientific level of evidence varies, but the recently published primary studies being of high quality certainly strengthen evidence in the area of direct communication intervention.

Direct interventions or training of the child has proved to have a positive impact on the development of the child with ASD as is stated in most, but not so sure in all, of the studies in the table. Exactly what is described to be affected differs in different studies, depending on the focus of the study, but to a large extent also on what have been measured in a particular study. It is more common that classical didactic programs report outcomes within the function- or activity-domain, often by the use of measures of intelligence (IQ) or language (different language tests). The child-directed naturalistic interventions more often describe outcomes in terms of activity or participation and use data of communication or interaction from video

the fairly large amount of indirect instruction in these programs.

questionnaires filled in blindly before-after intervention.

the education is complemented with direct intervention to the child.

**6.2. Direct interventions — Provision of training of the child**

analyses, parental questionnaires and interviews.

The results that will be shared in this book chapter concerns the studies that specifically involved children on the autism spectrum, which in total involved about half of the studies, or exactly 47 studies. The data from both literature searches was used: 30 studies from the review published in 2011 and 16 studies from the updated version of 2012.


*Appendix A.1*

The IEEE 33 bus EDS as shown in Figure A1 has been selected for analysis. As mentioned in Section 5, it is inferred that the 33-bus distribution system is analyzed for obtaining the locations and sizes. The branch and load data have been taken from [76].

**Figure A1.** The IEEE 33 bus EDS.

*Appendix A.2*

**Table A1.** Load distribution for 33 bus [52].

From Table A2, average failure rate, and unavailability can be determined as given in Equations (A1) and (A2).  Cost per kilowatt for Reliability worth estimation [78].


**Appendix A**

We plotted the Kilian index according to the data from the Lutz Kilian website, which showed the monthly index of the global real economic activity. This figure shows that fluctuations in global real economic activity are consistent with the anecdotal evidence. It is commonly accepted that when war breaks out and crises or threats occur, trade uncertainty rises and these events damage global economic activity.

**Figure A1.** The Kilian Index. **Note** This figure illustrates time-changing trend of the Kilian Index [15] from Jan. 1968 to Jun. 2019.


**Abstract**

Soybean (*Glycine max* [L.]) contributes 25% of the global edible oil. Globally, soybean area and production in 2020 were 127.9 million ha and 379.8 million tons, respectively. Soybean has got early acceptance as an important oilseed crop in India in with approximately 10–11 million ha area. Now, it has become a major crop by replacing the traditional and contemporary popular crops in nearly all parts of India. Climate change effects, like change in *Monsoon* pattern, increase in dry spell frequencies, heavy rainfall event during crop growth period, extended monsoon at harvesting stage, has drastically influenced the productivity of soybean, which needs attention to identify the constraints and accordingly adapt the climate-resilient technologies. The recent research conclusions revealed that the climate-resilient technologies like selecting suitable varieties, sowing within proper sowing window, broad bed furrow (BBF) method of sowing, dry spell management practices to reduce moisture stress, rainwater harvesting, and soil conservation through BBF method of planting, reuse of harvested and stored rainwater during moisture stress conditions, the adaptation of micro-irrigations systems for protective irrigation, intercropping in soybean, resource conservation techniques can mitigate the effects of climate change and enhance the productivity of soybean in a sustainable manner.

**Keywords:** broad bed and furrow, dry spell management, resilient technologies, soybean yield

### **1. Introduction**

Soybean cultivation and its use was started from the beginning of Chinas agriculture age. Its utilization for human consumption was mentioned [1] long ago 6000 years back in Chinese medical compilations. Soybean has meant for milk, meat, bread, cheese and oil from centuries ago to common people of China, Korea, Manchuria, Japan, Philippines and Indonesia. The center for origin of soybean is China while some reports second center as India [2–4]. In India initially, soybean has been traditionally grown in patches of the Kumaon Hills of Uttarakhand (earlier Uttar Pradesh), the Khasi Hills, the Naga Hills, Manipur, Himachal Pradesh, and parts of central India encompassing Madhya Pradesh.

During 2020 the global area and production of soybean was 127.9 million ha and 379.8 million tons respectively. India stands fifth rank in the area and production in the world after countries USA, Brazil, Argentina and China. The productivity of soybean in India is low (1.1 tons/ha) as compared to the world (2.3 tons/ha).

Rainfed agriculture produces much of the food consumed globally. It accounts for more than 95% of farmed land in Sub-Saharan Africa, 90% in Latin America, 65% in East Asia and 60% in South Asia. The rainfed agriculture across the world is being affected by climate change.

### **1.1 Indian situation**

On global map India lies between 8° N and 37°. In all climate over Indian subcontinent is dominantly tropical except Northern parts where the climate is temperate.  This is due to monsoon winds. Typical monsoon over India has two branches, i.e., Arabian sea branch and Bay of Bengal branch.

In Indian context soybean has occupied the position as major crop of India by replacing the traditionally grown major region-specific contemporary crops like cotton, paddy, and wheat. This has derived the agriculture completely new cropping systems also. Reasons of early popularity of the soybean crop in India are good demand of crop in international market, assured economic value of the crop along with the nutrient rich in both oil content (16–21%) and protein content (36–42%). Climatic requirements of soybean crop in more or less variations matches with existing climatic conditions over India which may be one of the reasons for steady performance of soybean in terms of production and productivity.

Based on productivity levels of soybean, total Indian geographical area is categorized in six agroclimatic zones which are Northern Hill Zone, Northern Plain Zone, Eastern Zone, North Eastern Hill Zone, Central Zone, and Southern Zone. The breeding for improving varieties with suitability and management practices specific to the particular zone are identified to achieve higher levels of productivity. In last years the area under soybean in India is constantly increasing with increase in productivity. In year 2020–2021 among various soybean growing states of India, Madhya Pradesh followed by Maharashtra were the first two states to grow soybean on 5.85 million ha and 4.32 million ha area respectively. In other states like Karnataka, Telangana, Gujarat, and Chhattisgarh there is considerable scope for the area enlargement (**Table 1**).

The average annual rainfall of India is 1192 mm, with spatial and temporal variability which delineate the Indian agriculture in to dry farming, dryland farming and rainfed farming. The major soil types of India are Vertisols, Inceptisols and Entisols. Vertisols are deep black cotton soils having swelling and shrinkage properties, good water holding capacity. In India soybean is promising and prominent rainfed crop where seasonal rainfall is 900 mm and soil type is vertisols. In some parts of India traditionally adopted cropping system was *Kharif* fallow followed by post-rainy wheat or chick pea, but soybean has substituted this cropping system as soybean followed by wheat or chick pea. Gain in the *kharif* season crop has bring out improvement of small and marginal farmers profitability, socio-economic condition. The small and marginal farmers are subjected to subsistence farming due to limited production inputs. Even under aberrant weather conditions soybean has maintained its steady performance in terms of profitable returns to farmers [5].

Indian Council of Agricultural Research—Indian Institute of Soybean Research, at Indore, Madhya Pradesh was established to provide centralized research to support *Climate-Resilient Technologies for Enhancing Productivity of Soybean in India DOI: http://dx.doi.org/10.5772/intechopen.104603*

### **Table 1.**

*State-wise expected area, production, and productivity of soybean 2021.*

soybean production system research with basic technology and breeding material. Under AICRPS (All India Coordinated Research Project on Soybean) system 102 improved soybean varieties have been developed which were suitable to different agroclimatic zones, and promising with high yields due to tolerance to various biotic and abiotic stresses.

After independence through green revolution, high yielding varieties, India achieved record breaking/higher food grain production and achieved self-sufficiency in cereals production. This achievement of the higher production was associated with several extensive problems which encounter to degradation of the natural resources and challenged sustainability. The concepts of conservation have gained importance due to the threat of resource degradation problems, the necessity to reduce production costs, increase productivity and profitability and make agriculture more inexpensive. Over exploitation of natural resources, conducive to unsustainable growth; these strategies need to change in coming years for increasing the sustainability. For Indian agriculture it is the time where it must search for new guidelines—may be through strategies, policies, and actions which must be accepted to move toward sustainability.

In recent past decades, at global level, rapid moves have been made in order to develop and spread the technologies which will conserve resources. Conservation of soil and rainwater can be achieved with change in land configuration, and method of planting like broad bed method of sowing, minimizing soil disturbance through restricted tillage. Adoption of conservation agriculture (CA) include the basic three pillars or principles which are

These principles can be effective possible ways towards the realization of the sustainability in agriculture and will help in achieving the goals of increasing productivity with prevention of further degradation of natural resources. To sustain soil fertility, improving fertilizer/water use efficiency, physical properties of soil, and

enhanced crop productivity, techniques of crop residues retention on the soil surface, organic and inorganic combined fertilization and involvement of legumes in crop rotation are essential. Above techniques coupled with minimum or no-tillage practices play a major role in conservation of natural resources. Thus, resource- conserving technologies can be used to enhance soil health, water, and nutrient use efficiency.