**Treatment of Bone Defects — Allogenic Platelet Gel and Autologous Bone Technique**

Dragica Smrke, Primož Rožman, Matjaž Veselko and Borut Gubina

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/55987


**7. Single unit plasmonic bowtie nano-antenna**

Bowtie shape PNAs (PBNAs) can transfer the light field efficiently by converting the light from external space into a subwavelength spectral region with the improvement at an optical wavelength in a tiny area between its antenna arms.

First of all, initial dimensions are selected to design primary bowtie shape nanoantenna by sitting the length of nano-antenna is (L), the width is (W), the thickness is (T), the apex width is (A), the gap width is (G) and the bowtie apex angle is (Θo) [30], as shown in **Figure 1a**.

The bowtie structure is normally illuminated by linearly polarized waveguide excitation source along the x-axis (x-polarization). The surrounding environment of the design structure is assumed to be air. as shown in **Figure 1b**.


Preface

This book discusses the behavior of several volcanoes worldwide. It refers to those volcanoes that are quiescent and/or active and that can transform the lives of those that live around them when they erupt. The development and application of new approaches and technologies will provide new visions about how volcanoes work so that a novel volcanic model can be built.

The authors who collaborated on this project have summarized their experience and present advances related to the assessment of hazards and risks associated with volcanic parameters. The book contains five chapters that cover important research aspects of hazardous volcanology. The first chapter is an introductory chapter prepared by the editor and looks at the present state of the art of volcanology with suggestions for the future of volcanic structures and the ability to forecast volcanic eruptions.

The next chapter presents the Jos and Biu Plateaux volcanic provinces occupying the northeastern half of Nigeria, bordering the Cameroon Volcanic Line, which has a conspicuously visible number of dormant volcanoes with no reported activity. The several incidences of volcanic eruptions along and close to the Cameroon Volcanic Line are pointers to the possible reactivation of any of the dormant volcanoes in Nigeria.

Chapter 3 presents experience of Deccan volcanism at 65 Ma when it moved over the Réunion hotspot, which altered lithospheric structures below the Kachchh rift zone. To quantify the influence of Deccan volcanism on the crust-mantle, this kind of study is very important to evaluate the difference between the components participating in the formation of such magmas.

Sang Koo Hwang illustrates the evolution of the Guamsan caldera associated with the Guamsan Tuff and rhyolitic intrusions in Chapter 4 and explains the evolution and formation of such caldera.

In Chapter 5, Leonel Vega, on the other hand, puts forward a new methodology for the case of volcanic risk computation. Most of the scientific, technical, and economic effort has been oriented towards the evaluation of threats, with a number of methodological considerations for assessing vulnerability and much less risk, so that integral volcanic risk can be computed.

The final chapter by the editor Angelo Paone studies the volcanic evolution, hazards, and risks of the Somma-Vesuvius volcano.

The editor expresses his thanks to all the participants for their valuable contributions and to Ms. Nina Kalinic Babic for her assistance in finalizing the book. Acknowledgment also goes to IntechOpen staff members for their help in completing this book and other publications for free access.

> **Angelo Paone and Sung-Hyo Yun** Pusan National University, South Korea

> > **1**

**Chapter 1**

but it is worth to try.

**1. Forecasting volcanic eruption**

Introductory Chapter: New

A volcano is a peculiar system where the evolution must be determined. Since a volcano is a complex and chaotic system, any volcanological information have to be taken in fully consideration in a broad volcanic model. Such task is not easy and many active and quiescent volcanoes must be watched attendally, and each volcanological parameter has to be studied and evaluate its influence on the broad hypothetically volcanic model at the unisono. This method could be a difficult endeavor,

A major issue in the study of active volcanoes is the link between eruption history, the changes in magma compositions and volumes observed on the surface, and the nature and the time scale of magma differentiation processes underground [1, 2]. It is the latter which determine the timing and the style of eruptions, and which are therefore fundamental to models of how particular volcanic systems behave and evolve, and hence determine hazard mitigation. The immediate targets are those volcanoes that are active, have a history of devastating eruptions, and are in highly populated areas. To make best use of the latest analytical technology, it is also important to work on a well-studied volcano with an established stratigraphy and rock composition. Studies of volcanic samples, experimental investigations, and theoretical modeling are providing insights into the dynamics of magmatic systems and how the plumbing system evolves with time, giving a physical framework with which to interpret volcanic phenomena. All the volcanic processes evolving before and during an eruption lead to the variation of geochemical and geophysical parameters [3]. Hence, computational and analytical facilities, instrumentation, and collection of comprehensive observational, geophysical, geochemical, and petrological datasets associated with recent volcanic activity have enormously improved our view on how volcanoes work [4]. Many active volcanoes have been studied in terms of volcanic forecasting using only some of these techniques. The challenge is to try to employ a volcanological methodology where the main chemical, petrologic, physical, and geophysical parameters are linked all together in order to build a framework where the history of magma ascent velocities, the time scales of magma differentiation, the past and present situation of the magmatic conduit, and the present state of degassing must be considered simultaneously. Such conceptual scenario can be commensurate with monitoring quiescent volcanoes, thus forecasting volcanic eruptions. The papers presented in this International Volcanological Special Issue consider the characteristic features of a single volcano and/or a province of volcanoes on earth, in terms of a future volcanic activity. The technical methods used are wide and innovative as well as traditional concerning the knowledge presented for each paper and therefore worth to study. In this book by the title "Forecasting Volcanic Eruptions," we collect some example of

Advances and Challenges

*Angelo Paone and Sung-Hyo Yun*


**10. Conclusion**

NPC is a very interesting within the other head and neck cancers, occurring in young patients non-smokers/non drinkers and significant improvement of therapeutic results have been reached during the last 30 years, 5 years-OS increasing from 20-30% to more than 75% with the recent protocols of CT-RT or PCT followed by CT-RT that included taxanes (Boussen et al, 2010, Chan et al,2010). Overexpression of EGRF, present in more than 70% of NPC leads to the use of Cetuximab as adjuvant concomitant or maintenance therapy (Yang Y et al, 2011). Anti-angiogenesis therapies like Pazopanib have been also tested without proven efficacy(Lim et al,2011). The significant survival improvement made NPC a more curable disease and efforts were made to reduce late sequelae specially in children and adolescents and to affect minimally quality of life after combined chemo-radiotherapy (Fang et al,2011;Marucci et al,2011;Shueng et al,2011).

## **11. References**

Al-Sarraf M, LeBlanc M, Giri PG et al. (1998).Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. *J Clin Oncol*,16,1310–1317.

found to be a significant prognostic factor on LRRFS (p=0.03). However Nasopharyngeal PTV alone is missing the volume of satellite cervical nodes that have probably an important

NPC failures are mainly metastatic, to bones, lungs and liver and loco-regional relapses became more rare due to the high loco-regional control rate obtained by loco-regional RT (Leung et al,2005; Cvitkovic et al,1993). In metastatic situations, NPC remains chemosensitive to cisplatin, adriamycin, 5Fluorouracil or more recently taxanes, gemcitabine or oral capecitabine(Boussen et al,1991,2010;You et al,2011;Bensouda et al,2011). Prolonged survival after palliative CT and/or RT could be observed in patients with bone metastases in case of bone MTS only and less than 4 sites involved (Fandi et al,2000;Cao et al,2011). In isolated bone metastases, prolonged responses under biphosphonates plus CT have been also reported, with a significant reduction of skeletal events and better (11.5 vs 5.5 months, P < 0.001) progression-free survival and overall survival (23.5 vs. 17.5 months, P < 0.001) of combined vs chemotherapy alone group. (Jin et al,2011). Even in case of lung MTS disease, different prognostic groups could be identified according to size and numbers of metastatic

Some efforts have been done oriented for early detection in relatives of patients considered at high risk for NPC, according to their viral DNA and anti-EBV profile (Baizig et al,2011;Liu et al,2011). Sophisticated endoscopic technique have been also tested to detect easily early

NPC is a very interesting within the other head and neck cancers, occurring in young patients non-smokers/non drinkers and significant improvement of therapeutic results have been reached during the last 30 years, 5 years-OS increasing from 20-30% to more than 75% with the recent protocols of CT-RT or PCT followed by CT-RT that included taxanes (Boussen et al, 2010, Chan et al,2010). Overexpression of EGRF, present in more than 70% of NPC leads to the use of Cetuximab as adjuvant concomitant or maintenance therapy (Yang Y et al, 2011). Anti-angiogenesis therapies like Pazopanib have been also tested without proven efficacy(Lim et al,2011). The significant survival improvement made NPC a more curable disease and efforts were made to reduce late sequelae specially in children and adolescents and to affect minimally quality of life after combined chemo-radiotherapy (Fang

Al-Sarraf M, LeBlanc M, Giri PG et al. (1998).Chemoradiotherapy versus radiotherapy in

patients with advanced nasopharyngeal cancer: phase III randomized Intergroup

prognostic value.

**8. Recurrent/metastatic disease**

nodules (Cao X et al, 2011).

**10. Conclusion**

**11. References**

**9. Effective screening for NPC?**

stages of NPC (Lin et al,2011, Lin et al,2011).

et al,2011;Marucci et al,2011;Shueng et al,2011).

study 0099. *J Clin Oncol*,16,1310–1317.

Update on Medical Therapies of Nasopharyngeal Carcinoma 187

Marucci L, Marzi S, Sperduti I, Giovinazzo G, Pinnarò P, Benassi M, Strigari

Qiu C, Yang N, Tian G, Liu H. (2011). Weight loss during radiotherapy for nasopharyngeal

Sham JS, Choy D.(1991). Prognostic value of paranasopharyngeal extension of

Shueng PW, Shen BJ, Wu LJ, Liao LJ, Hsiao CH, Lin YC, Cheng PW, Lo WC, Jen YM, Hsieh

Sun LM, Epplein M, Li CI, Vaughan TL, Weiss NS. (2005). Trends in the Incidence Rates of

Teo P, Shiu W, Leung SF, Lee WY(1992). Prognostic factors in nasopharyngeal carcinoma

Tse LA, Yu ITS , Mang OWK, Wong SL.(2006). Incidence rate trends of histological subtypes

Wei K, Xu Y, Liu J, Zhang W, Liang Z. (2010). No incidence trends and no change in

Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, Deng XW, Lu TX, Cui NJ, Zhao C.

Xu L, Pan J, Wu J, Pan C, Zhang Y, Lin S, Yang L, Chen C, Zhang C, Zheng W, Lin S, Ni X,

TNM Classification of malignant tumors. 7th edition. Union for International Cancer

Xiao WW, Huang SM, Han F et al. (2011). Local control, survival, and late toxicities of

Yang Y, Xuan J, Yang Z, Han A, Xing L, Yue J, Hu M, Yu J. (2011). The expression of

nasopharyngeal carcinoma. *Radiat Oncol*,13,6(August 2011),95.

*Epidemiol*,162,12,(December 2005),1174-1178.

of a phase 2 study. *Cancer*,117,9,(May 2011),1874-83.

and radiation break. *Radiother Oncol. ,*96,1,(July 2010),94-9.

Control. .(2009). Geneva. http://www.uicc.org/node/7735.

term results of a phase 2 study. *Cancer* 2011 May 1;117(9):1874-83.

*Asian Pac J Cancer Prev*,11,6,1595-9.

radiation therapy for nasopharyngeal cancer. *Head Neck,*(Mar2011).

2011),873-9.

*Neck,*13,298-310

*Oncol*,23,79-93

method for nasopharyngeal carcinoma: A two-stage design with a preliminary performance study and a Mass screening in southern china. *Int J Cancer*,(Aug 2011).

L.(2011).Influence of intensity-modulated radiation therapy technique on xerostomia and related quality of life in patients treated with intensity modulated

carcinoma: a prospective study from northern china. *Nutr Cancer*,63,6,(Aug-Sep

nasopharyngeal carcinoma on local control and short-term survival. *Head*

CH. (2011). Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced

Nasopharyngeal Carcinoma among Chinese Americans Living in Los Angeles County and the San Francisco Metropolitan Area, 1992–2002. *Am. J.*

investigated by computer tomography--an analysis of 659 patients. *Radiother*

of nasopharyngeal carcinoma in Hong Kong. *Br J Cancer*,95,9,(Nov 2006),1269–1273.

pathological proportions of nasopharyngeal carcinoma in Zhongshan in 1970-2007.

(2011). Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-term results

Kong FM.(2010). Factors associated with overall survival in 1706 patients with nasopharyngeal carcinoma: significance of intensive neoadjuvant chemotherapy

locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: long-

epidermal growth factor receptor and Ki67 in primary and relapse nasopharyngeal

Ekenel M, Keskin S, Basaran M, Ozdemir C, Meral R, Altun M, Aslan I, Bavbek SE.

Fang FM, Tsai WL, Lee TF, Liao KC, Chen HC, Hsu HC.(2010). Multivariate analysis of

Fountzilas G, Ciuleanu E, Bobos M et al. (2011). Induction chemotherapy followed by

Gao F, Wee J, Wong HB, Machin D. (2010). Quality-of-life-adjusted survival analysis of

Hui EP, Ma BB, Leung SF et al. (2009). Randomized phase II trial of concurrent cisplatin

Jin Y, An X, Cai YC, Cao Y, Cai XY, Xia Q, Tan YT, Jiang WQ, Shi YX. Zoledronic acid

Lee AW, Poon YF, Foo W et al. (1992). Retrospective analysis of 5037 patients with

Lee AW, Tung SY, Chua DT et al. (2010). Randomized trial of radiotherapy plus concurrent-

nasopharyngeal carcinoma. J Natl Cancer Inst,102,15,(Aug 2010),1188-98. Leung TW, Tung SY, Sze WK et al.(2005) Treatment results of 1070 patients with

Lim WT, Ng QS, Ivy P et al. (2011). Tan A Phase II Study of Pazopanib in Asian Patients

Lin B, Bergholt MS, Lau DP, Huang Z. (2011). Diagnosis of early stage nasopharyngeal

Liu Y, Huang Q, Liu W et al. (2011). Establishment of VCA and EBNA1 IgA-based

group phase II trial 0225. *J Clin Oncol* 27,22,(August 2009),3684-90.

nasopharyngeal cancer. *Int J Radiat Oncol Biol Phys,*78,454-60.

nasopharyngeal carcinoma. *J Clin Oncol* 2009;27:242-9.

of failure. *Int J Radiat Oncol Biol Phys*,23,2,261-70.

carcinoma. (2011). *Head Neck*,33,4,(April 2011)591-4.

advanced nasopharyngeal carcinoma. *Oral Oncol* 2011 Jul;47(7):660-4. Fandi A, Bachouchi M, Azli N, Taamma A, Boussen H, Wibault P, Eschwege F, Armand JP,

2000),1324-30.

*Neck*,27,555-65.

2011),5481-9.

Radiother Oncol,97,2, (Nov 2010),263-9.

with biomarker evaluation. *Ann Oncol* Apr 27.

Induction chemotherapy with docetaxel and cisplatin is highly effective for locally

Simon J, Cvitkovic E.(2000). Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type. *J Clin Oncol* 18,6,(Mar

quality of life outcome for nasopharyngeal carcinoma patients after treatment.

concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG)

concurrent chemo radiotherapy for locally advanced (nonmetastatic)

radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced

combined with chemotherapy bring survival benefits to patients with bone metastases from nasopharyngeal carcinoma. *J Cancer Res Clin Oncol* 2011 Aug 13. Lee N, Harris J, Garden AS et al.(2009). Intensity-modulated radiation therapy with or

without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology

nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns

adjuvant chemotherapy vs radiotherapy alone for regionally advanced

nasopharyngeal carcinoma: an analysis of survival and failure patterns. *Head*

with Recurrent/Metastatic Nasopharyngeal Carcinoma. *Clin Cancer Res,*17,16,(Aug

carcinoma using ultraviolet autofluorescence excitation-emission matrix spectroscopy and parallel factor analysis. *Analyst,136,19*,(Oct 2011),3896-903. Lin YC, Wang WH. Narrow-band imaging for detecting early recurrent nasopharyngeal

combination by enzyme-linked immunosorbent assay as preferred screening

method for nasopharyngeal carcinoma: A two-stage design with a preliminary performance study and a Mass screening in southern china. *Int J Cancer*,(Aug 2011).

cancer: a micro-evidence for anti-EGFR targeted maintenance therapy. *Med Oncol*,2011 Jul 23.

**11**

*Taiwan*

Shih-Shun Chen

 **Potential Therapeutic Molecular Targets**

Nasopharyngeal carcinoma (NPC) is the leading cause of death in Southeast Asian populations, especially among Chinese people (338). The specific type of NPC is defined by the World Health Organization and classified histologically as either type I (keratinizing squamous cell carcinoma), type II (non-keratinizing squamous cell carcinoma), or type III (undifferentiated carcinoma) (263). Etiologic factors associated with NPC development are classified according to three determinants, including genetic susceptibility, Epstein-Barr virus (EBV) infection, and environmental exposure to carcinogens (45, 337). Evidence has indicated that EBV infection is implicated in the development of type II and III and is observed particularly in Asia (50, 61, 205, 230). EBV infection is generally not detected in type I NPC patients, especially in non-endemic areas (221, 342). Potential risk factors significantly associated with the initiation and development of type I NPC are cigarette smoking and alcohol consumption (35, 225, 295, 301). However, increasing evidence indicates that EBV appears to be the predominant risk factor associated with the initiation and development of NPC, regardless of histological type (17, 20, 300). In particular, EBV infection is an important event in the early stage of the NPC carcinogenesis process before tumor formation (101). Clinically, NPC exhibits a high incidence of lymph node spread and distant metastasis that is correlated with a poor prognosis, even when employing radiation therapy and chemotherapy (43, 260, 326). In the search for new substances with anti-tumoral effects, many natural compounds from dietary plants, such as herb and fruit extracts, have been shown to inhibit NPC proliferation, invasion, metastasis, and angiogenesis both *in vitro* and *in vivo*. This review summarizes the molecular mechanisms of EBV infection in NPC development as well as the role of natural compounds in the regulation of multiple cellular

pathways and their clinical importance for the prevention and treatment of NPC.

Virus binding to the surface of a target cell is a major determinant of cellular tropism and is a critical step in viral pathogenesis. This early event initiates the virus replication cycle by the attachment of the virus to specific receptor (s) and leads to the release of the viral genome into the cytoplasm of the target cell. It is believed that EBV infection is initiated by

**2. The molecular mechanisms of EBV infection and the effects on**

**NPC growth and metastasis**

**1. Introduction**

**for Nasopharyngeal Carcinoma**

*Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung,*


**3. Experimental method**

### **3.1 Experimental setup**

The test model was set in AF6116 (M = 0.1) subsonic wind tunnel located at the Hanoi University of Science and Technology, which was of a blowdown type with a closed test section (0.4 0.5 1.0 m3 ). The wind speed could be arbitrarily varied up to 30 m/s, where the Reynolds number based on wing root chord was 106 , which was driven by an 8 kW electric motor.

**Wing 1 (non-structure) Wing 2 (with structure)**

Chord length 300 mm 300 mm Root chord length 500 mm 500 mm Tip chord length 100 mm 100 mm Profile NACA65A004 NACA65A004 Taper ratio 0.5 0.5

*Experimental models. (a) Wing model. (b) Wing with support. (c). Broken wing.*

*Research on Aeroelasticity Phenomenon in Aeronautical Engineering*

*DOI: http://dx.doi.org/10.5772/intechopen.91748*

Mass 5.1 g 11.6 g

**Table 4.** *Wing models.*

**Figure 10.**

**Table 5.**

**Figure 11.**

**65**

**Attack angle (0**

Material Balsa wood Balsa wood, carbon rod, hard wood

0 20 22 37.38 5 17.8 20.5 32.22 10 15.2 19.5 30.31

*Flutter characteristics at different attack angles—Non-structure wing.*

*Force at the wing root of the non-structure wing—Attack angle 10°.*

**) Velocity of first oscillation (m/s) Flutter velocity (m/s) Frequency (Hz)**

Flutter characteristics were determined with the help of the frequency meter and load cell, which allowed to specify the flutter frequency and root wing force, respectively. The oscillated frequency was measured by the DT-2234C+ frequency meter. The signal of measured frequency was averaged by five measurements. The force applied to the wing was measured by load cell system. In the experimental aeroelastic analysis, the flutter frequency and the flutter amplitude were measured at different velocities ranging from 10 to 30 m/s using an oscillator generator system.

### **3.2 Wing model**

Two wing models with the parameter and dimension are shown in **Figure 10** and **Table 4**. The non-structure wing had only balsa wood, while the structure wing had balsa wood for skin and carbon rod and hard wood for the inner parts.

#### **3.3 Results**

Experimental results showed that a flutter phenomenon appeared with the non-structure wing (broken wing in **Figure 10c**), but this phenomenon did not happen with the structure wing model. It could be explained by the more durability of structure wing than that of the non-structure wing with the testing range of velocity. Experiments also demonstrated that the combination of multiple materials to more durability of structure of wing could be highly effective in preventing flutter phenomenon [18].

The measurement results of the non-structure wing were shown in **Table 5**. When the attack angle increased, the velocity of first oscillation, flutter velocity, and frequency decreased.

**Figure 11** resumed the measurement of the force at the wing root in varying velocities from zero to flutter velocity and more by using the load cell system. After increasing the air velocity from zero to the limit of non-structure wing, the limit

*Research on Aeroelasticity Phenomenon in Aeronautical Engineering DOI: http://dx.doi.org/10.5772/intechopen.91748*

#### **Figure 10.**

This remark illustrated that the developed solution could be used to specify the

**Velocity (m/s) Density (kg/m3**

Baskut [6] 171.84 0.3987 21.67 Yates [13] 172.5 0.42770 20.39 Simulation 174.257 0.43164 18.87 Relative error with [13] 1% 1% 7%

The test model was set in AF6116 (M = 0.1) subsonic wind tunnel located at the Hanoi University of Science and Technology, which was of a blowdown type

varied up to 30 m/s, where the Reynolds number based on wing root chord was 106

Flutter characteristics were determined with the help of the frequency meter and load cell, which allowed to specify the flutter frequency and root wing force, respectively. The oscillated frequency was measured by the DT-2234C+ frequency meter. The signal of measured frequency was averaged by five measurements. The force applied to the wing was measured by load cell system. In the experimental aeroelastic analysis, the flutter frequency and the flutter amplitude were measured at different velocities ranging from 10 to 30 m/s using an oscillator generator

Two wing models with the parameter and dimension are shown in **Figure 10** and **Table 4**. The non-structure wing had only balsa wood, while the structure wing

Experimental results showed that a flutter phenomenon appeared with the non-structure wing (broken wing in **Figure 10c**), but this phenomenon did not happen with the structure wing model. It could be explained by the more durability of structure wing than that of the non-structure wing with the testing range of velocity. Experiments also demonstrated that the combination of multiple materials to more durability of structure of wing could be highly effective in preventing

The measurement results of the non-structure wing were shown in **Table 5**. When the attack angle increased, the velocity of first oscillation, flutter velocity,

**Figure 11** resumed the measurement of the force at the wing root in varying velocities from zero to flutter velocity and more by using the load cell system. After increasing the air velocity from zero to the limit of non-structure wing, the limit

had balsa wood for skin and carbon rod and hard wood for the inner parts.

). The wind speed could be arbitrarily

**) Frequency at flutter (Hz)**

,

transonic flutter characteristics with errors less than 10%.

with a closed test section (0.4 0.5 1.0 m3

which was driven by an 8 kW electric motor.

**3. Experimental method**

*Flutter characteristics at M = 0.499.*

**3.1 Experimental setup**

system.

**Table 3.**

*Aerodynamics*

**3.2 Wing model**

**3.3 Results**

**64**

flutter phenomenon [18].

and frequency decreased.

*Experimental models. (a) Wing model. (b) Wing with support. (c). Broken wing.*

#### **Table 4.**

*Wing models.*

#### **Table 5.**

*Flutter characteristics at different attack angles—Non-structure wing.*

**Figure 11.**

*Force at the wing root of the non-structure wing—Attack angle 10°.*

velocity of non-structure wing was found at 19.5 m/s. The load at the wing root of this wing at flutter velocity is shown in **Figure 12**. The maximum force was 5.44 N, and the minimum force was 4.32 N.

The frequencies of the first and second modes of the non-structure wing were higher than those of the structure wing, while the frequencies of third and fourth mode of structure wing were higher than those of non-structure wing (**Table 6**). Considering both wings in the first mode of oscillation, when the force was applied to the wing, the amplitude of the non-structure wing was higher than that of the structure wing (**Figure 13**). In conclusion, the non-structure wing was easier to

Fluid flow and deformation of structure were governed by the following equa-

ð5Þ

ð6Þ

ð7Þ

ð8Þ

ð9Þ

ð10Þ

resonate than the structure wing.

*DOI: http://dx.doi.org/10.5772/intechopen.91748*

tions with assumption of linear elastic structure [11]:

*Research on Aeroelasticity Phenomenon in Aeronautical Engineering*

**4. IBM method**

**4.1 Methodology**

where:

**67**

u: fluid velocity vector p: fluid pressure

Re: Reynolds number Uc: displacement velocity ωp: angular velocity xc: center of gravity θp: rotation of wing r mp: mass of wing

f: force that affected on wing

Ip: inertial moment of wing

F: force created by fluid passing through the wing T: moment created by fluid passing through the wing

To solve out these equations using IBM method, the most important was that the

velocity of fluid at fluid-solid interface was equal to the velocity of the wing. It means that the interaction force (f) between the wing and fluid was calculated such that the boundary condition of fluid was satisfied on the surface of the wing. IBM method used the Cartesian grid and immersed boundary that were illus-

trated in **Figure 14**, in which the moving surface of wing was described by

With structure wing, different modes of vibration appeared depending on the characteristics of the structure as remarked in [8]. With the help of the oscillator generator system, the specific oscillation frequencies of the first four modes were estimated as shown in **Table 6**.

**Figure 12.**

*Force at the wing root of the non-structure wing—Attack angle 10° and velocity 19.5 m/s.*

#### **Table 6.**

*Specific oscillation frequency of the non-structure and structure wings.*

**Figure 13.** *Amplitude of oscillation of the structure wing—Mode 1.*

*Research on Aeroelasticity Phenomenon in Aeronautical Engineering DOI: http://dx.doi.org/10.5772/intechopen.91748*

The frequencies of the first and second modes of the non-structure wing were higher than those of the structure wing, while the frequencies of third and fourth mode of structure wing were higher than those of non-structure wing (**Table 6**). Considering both wings in the first mode of oscillation, when the force was applied to the wing, the amplitude of the non-structure wing was higher than that of the structure wing (**Figure 13**). In conclusion, the non-structure wing was easier to resonate than the structure wing.


**9. The challenges of CFRD**

The distinct glucose profile typically seen in CFRD presents clear challenges not only for establishing the diagnosis in the first place but also for managing the condition in general.

### **9.1. Dietary considerations**

The primary aim of nutritional management in relation to CFRD is the achievement of a normal nutritional status [3]. CFRD has different and conflicting dietary recommendations from that of type 1 or type 2 diabetes. CFRD patients have up to 150% the calorific requirements of other diabetic patients and require a diet containing both high fat and protein levels.

Patients with CF require regular snacks in between meals in order to meet their increased metabolic requirements and often resort to consuming foodstuff that is high in refined sugars – such as so called 'energy drinks' – in order to maintain their weight, especially as it obviates the need to medicate with enzyme supplements [75].

Ingestion of products that contain even modest quantities of highly refined sugar can not only cause glucose excursions but may also precipitate a reactive hypoglycaemic episode – a phenomenon that can be seen during 7-15% of diagnostic OGTTs [24, 76].

The use of a diet rich in carbohydrates that have a low glycaemic index (GI) is encouraged in type 2 diabetics both to aid blood glucose control and weight reduction, however little robust evidence exists of benefit from a similar approach in a CFRD population and there are concerns that low GI diets might lead to inappropriate weight loss in this group [72].

Recommendations from American researchers have suggested that carbohydrate counting may have a role in CFRD [3] however in other countries this approach is reserved for T1DM alone, with the CF dietetic community in the United Kingdom favouring regular meals and snacks containing a mixture of both complex and refined carbohydrates be taken with or just after eating other foods [75]– an approach that anecdotally can reduce both the post-prandial glucose excursions as well as subsequent reactive hypoglycaemia occurring.

Dietary assessment is therefore an important part of the management of CFRD particularly to assess and modify refined sugar intake whilst ensuring overall calorific requirements and a healthy weight are maintained.

### **9.2. Exercise**

**•** Clinical history - number of admissions with reasons

**•** Hypoglycaemia – identify cause and optimise treatment

**•** Foot examination - pedal pulses, sensory and vibration check.

**•** Frequency of distal intestinal obstruction syndrome (DIOS)

**•** Urea and electrolytes, creatinine clearance (selected cases)

Additionally, annual screening is an opportunity to identify educational gaps and discuss how

The distinct glucose profile typically seen in CFRD presents clear challenges not only for establishing the diagnosis in the first place but also for managing the condition in general.

The primary aim of nutritional management in relation to CFRD is the achievement of a normal nutritional status [3]. CFRD has different and conflicting dietary recommendations from that

**•** Full dietetic review - Meals, snacks, enzymes, supplements, feeds.

**•** Height, weight and BMI

100 Cystic Fibrosis in the Light of New Research

**•** Pulmonary function

**•** Alcohol and smoking

**•** Sexual dysfunction

**•** Insulin therapy

**•** Injection technique. **•** Insulin site check

**•** Psychosocial support

**•** HbA1c

**•** Lipid profile

**•** Home blood glucose monitoring.

**•** Urine sample for Microalbuminuria

**•** Retinopathy screening referral

**9. The challenges of CFRD**

**9.1. Dietary considerations**

the patient is coping with their CFRD.

**•** Blood pressure

**•** Exercise

Regular exercise forms an important cornerstone of the general management of CF and is widely advocated [46] although direct evidence that it specifically improves overall blood sugar control in CFRD is lacking [77] although there is an on-going trial exploring this currently [78] CFRD patients need to be aware of the risk of precipitating hypoglycaemia during exercise and should be educated about extra monitoring during times of exertion.

### **9.3. Liver disease**

CF affects all of the major organs in the body including the liver and the prevalence of CFRD is higher in patients who have liver disease [79]. As discussed previously significant liver disease may lead to a reduction in hepatic glycogen stores, exacerbating the risk of sympto‐ matic hypoglycaemia developing and potentially reducing the response to exogenous glucagon used to treat such episodes. In addition, although it may be difficult to quantify, CFliver disease could lead to subtle impairments of hepatic insulin secretion and catabolism which may contribute to the overall dysglycaemia suffered by this group [79].

### **9.4. Hypoglycaemia**

As mentioned elsewhere in this chapter hypoglycaemia is not uncommon in CFRD [24]. Furthermore, it has been demonstrated that hypoglycaemia awareness is also impaired as a result of frequent subclinical hypoglycaemic episodes and a diminished glucagon response [32]. Therefore, careful consideration must be given to when blood sugar monitoring is carried out as well as the timing, type and amount of insulin used for treatment.

### **9.5. Corticosteroids**

Oral corticosteroids (e.g. prednisolone) are frequently used during pulmonary exacerbations in CF, and the concomitant elevation in blood glucose may necessitate a change in diabetes management in these patients. Patients may also require increased supervision and treatment during times of infection where blood glucose levels often fluctuate rapidly. There is evidence that CF patients with normoglycaemia exhibit diabetic glucose tolerance during pulmonary exacerbations [80]. This is likely to be due to the stress of infection and inflammation that unmasks the early alterations in glucose homeostasis [81]. Additionally, when infection subsides and patients stop corticosteroids, blood glucose can dramatically drop causing hypoglycaemia and careful support and advice is required during this time.


**Symmetries in Quantum Mechanics**

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**G. Jordan Maclay**

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**8. Conclusions**

As it is an urgent call for upgrading wheat production under increasing potentiality of drought events, wheat breeders of Bangladesh need to emphasize on integrating more breeding techniques to make drought tolerant varieties. Majority of the breeding approaches here are concentrating on conventional techniques. So, it is high time to combine the conventional breeding methods with the modern techniques to develop wheat genotypes for the next generation. New advanced screening, hybridization and selection techniques shall need to be incorporated with conventional techniques. To maximize the breeding efficiency for drought tolerance in wheat, advanced precision phenotyping accompanied by genetic and molecular approaches should be integrated in breeding programs.


**11. Future Prospects and Conclusions**

The current review discussed the biological synthesis methods in depth with emphasis on the lichen-mediated synthesis of NPs. The biological synthesis of NPs has recently become an increasingly active area of research. Through exhibiting several advantageous qualities and numerous potential applications, biological synthesis methods of NPs have proven to be superior to the traditional chemical and physical methods. These qualities include being cost effective, eco-friendly, and vastly applicable in biomedical fields due to biocompatibility. Lichen species are seldom considered as biomachinery for the biofabrication of NPs. In this review, we have highlighted the potential of these organisms as natural biofactories for NP formation. The symbiosis between fungi and cyanobacteria or algae or sometimes plants makes lichen a promising alternative biomachinery for NPs fabrication. Due to the variation in their biomolecule contents and structures, which are responsible for reducing metal ions into NPs. Devasena et al. reported that lichen-mediated synthesis NPs are distinguished from other alternative biological methods by being lesser toxic and needing low-processing conditions [161]. Lichen species have a reducible activity to fabricate different types of NPs, including gold (Au)-NPs, silver (Ag)-NPs, metal oxide-NPs such as iron oxide- and zinc oxide-NPs, and other nanomaterials such as bimetallic alloys (Au-Ag NPs) and nanocomposites such as ZnO@TiO2@SiO2 and Fe3O4@SiO2. These biogenic NPs have significant antimicrobial activities against both Gram-positive and Gram-negative bacteria, and fungi, and they also display mosquitocidal activity. Additionally, these NPs

act as potential catalytic materials, bioremediatory agents for heavy metals, antidiabetics, antioxidants, and neuroprotection agents against neurotoxin.

Extending the utilization of lichen-mediated green synthesis methods and exploring the optimum conditions of these processes to fabricate applicable, bioactive, scalable, and biocompatible nanoproducts may lead to the development of novel green NPs with unique physicochemical and biological features that can be applied in different sectors, including agriculture, industry, medicine, biotechnology, and pharmaceutics. Moreover, there remain many barriers against the biological synthesis process, including toxicity and agglomeration, polydispersity, stability, and the nonuniform size of NPs. These issues can be solved by increasing the optimization studies for green synthesis of NPs to obtain the desirable NPs. Additionally, exploring the synthesis mechanism of NPs using natural sources will facilitate the development and launch of nanodrugs in different fields.

**Author Contributions:** Conceptualization, R.S.H.; methodology, R.S.H., L.B. and M.A.A.; software, R.S.H. and M.A.A.; investigation, R.S.H. and L.B.; data curation, R.S.H., L.B. and M.A.A.; writing original draft preparation, R.S.H. and L.B.; writing—review and editing, R.S.H. and L.B.; visualization, R.S.H.; supervision, N.E.A., M.M.B.-M. and M.I.A.-Z.; project administration, R.S.H.; funding acquisition, M.M.B.-M. and M.I.A.-Z. All authors have read and agreed to the published version of the manuscript.

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

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data supporting this article are shown in Figures 1–7 and one table. The data sets analyzed in the present study are available from the corresponding author upon reasonable request.

**Acknowledgments:** This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.

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

#### **References**


**7. Intratympanic delivery methods**

There is no standard protocol for IT corticosteroid injections; the frequency of injections, concentration and type of corticosteroid. Method of injection is determined by the individual surgeon.

Multiple intratympanic delivery methods are descripted:

**Syringe delivery is a** simple method. However, direct injections do not allow for prolonged delivery. We can anesthetize the tympanic membrane with 10 percent Xylocaine. A drop of phenol on the ear drum is one method. Another is a topical anesthetic such as "Emla" cream. The drug is injected, left in the middle ear for 30 minutes.

The myringotomy is placed in the most superior and anterior location to allow maximal filling of the middle ear space with the corticosteroid solution while the patient is supine. Placement of the tube eliminates the need for a new myringotomy for each subsequent injection. For injection, we use a 25-gauge spinal needle attached to a 1-mL tuberculin-type syringe. To equalize pressure, two needle punctures were made in the anterior superior quadrant of the tympanic membrane, the first for injection and the second (superior) for air escap. The initial injection was followed by a second injection about 15 minutes later for a total volume of approximately 0.5 mL. The patient remained supine for 30 to 40 minutes, with the head turned to the side and the injected ear upright, and was instructed to swallow as little as possible to help maintain the fluid in the middle ear space for longer duration.

**Microwick** is the polyvinyl acetate wick (1 mm diameter by 9 mm length). It absorbs medication and transports it directly to the RWM. It's placed through a tube, at the round window niche. It allows instillation by the patient himself at home. The MicroWick should be removed or replaced after 4 weeks of treatment to prevent it from becoming adherent to the mucosa of the round window (26).

**Microcatheter** is composed of two tubes: one for injection and the other for the return of excess liquid. It ends with a bulge that is placed at the round window niche under general anesthesia. Some researchers propose to link the catheter to a pump. This would allow continuous irrigation and delivery of the product constantly at the round window.


*Article* **A WoT Platform for Supporting Full-Cycle IoT Solutions from Edge to Cloud Infrastructures: A Practical Case**

#### **Rafael Pastor-Vargas 1,***∗***, Llanos Tobarra 1, Antonio Robles-Gómez 1, Sergio Martin 2, Roberto Hernández 1 and Jesús Cano 1,3**

Received: 22 May 2020; Accepted: 2 July 2020; Published: 5 July 2020

**Abstract:** Internet of Things (IoT) learning involves the acquisition of transversal skills ranging from the development based on IoT devices and sensors (edge computing) to the connection of the devices themselves to management environments that allow the storage and processing (cloud computing) of data generated by sensors. The usual development cycle for IoT applications consists of the following three stages: stage 1 corresponds to the description of the devices and basic interaction with sensors. In stage 2, data acquired by the devices/sensors are employed by communication models from the origin edge to the management middleware in the cloud. Finally, stage 3 focuses on processing and presentation models. These models present the most relevant indicators for IoT devices and sensors. Students must acquire all the necessary skills and abilities to understand and develop these types of applications, so lecturers need an infrastructure to enable the learning of development of full IoT applications. A Web of Things (WoT) platform named Labs of Things at UNED (LoT@UNED) has been used for this goal. This paper shows the fundamentals and features of this infrastructure, and how the different phases of the full development cycle of solutions in IoT environments are implemented using LoT@UNED. The proposed system has been tested in several computer science subjects. Students can perform remote experimentation with a collaborative WoT learning environment in the cloud, including the possibility to analyze the generated data by IoT sensors.

**Keywords:** web of things; IoT learning; cloud computing; protocols; virtualization; instructional design


**5.1 Non-pharmaceutical treatment options**

Ptosis may be improved by eyelid tape or crutches; however, patients often are intolerant of these approaches finding them uncomfortable. Also, scleral irritation may occur by exposure and lead to drying or abrasion. Visual occlusive devices, such as eye patches or opaque contact lenses, eliminate diplopia but reduce the visual field. Custom corrective lenses with prisms may correct diplopia temporarily, but because patients with OM have fluctuation of their visual axes, they require frequent correction of their prism. Prism therapy may be considered in patients with stable strabismus for six months to a year. Eye muscle surgery may be beneficial in rare patients when a fixed strabismus occurs and non-variable ptosis (Ohtsuki et al. 1996; Bentley et al. 2001). Botulinum toxin may also be considered to correct ocular alignment by chemodenervation of the involved extraocular muscles, but it must be used cautiously given the potential for systemic neuromuscular transmission blockade. Although there are challenges associated with the treatments, non-pharmacological options may be favored by some patients and be the only options for patients with disease resistant to pharmacological treatments.

Ocular Myasthenia Analysis of Diagnostic and Treatment Options 113

percentage of patients will have symptom recurrence. Patients will need an increase in dose when symptoms recur. Most patients require maintenance doses for years, which should be the lowest possible to prevent recurrence of visual complaints. More than three-quarters of patients experience significant improvement (Evoli et al. 1988; Sommer et al. 1997; Tackenberg et al. 2001; Kupersmith and Ying 2005). To reduce corticosteroid complications every other day dosing of prednisone may be used. Patients should be instructed to take a single morning dose, which mimics the diurnal peak of endogenous corticosteroid. Patients need to be educated about steroid side effects, which include weight gain, glucose tolerance, hypertension, osteoporosis, insomnia, anxiety, depression, and the numerous other complications of prednisone. The neurologist or ophthalmologist should work with the

Based on retrospective analysis, corticosteroids may delay or prevent the progression of OM to generalized MG (Agius 2000; Kaminski and Daroff 2000; Kupersmith 2004). However, there has not been a randomized, controlled trial to assess whether steroids have a disease modifying effect (Gilbert et al. 2007; Gilbert and Savino 2007). Future studies should consider visual outcome and quality of life to determine whether the benefits of

Some patients will not respond to corticosteroids, have contraindications to their use, or have intolerable adverse effects necessitating use of other immunotherapies (Tackenberg et al. 2001). Assessment of efficacy for immunosuppressives specific to treatment for OM is extremely limited and is entirely based on retrospective investigation. Support for their use also derives from administration for the generalized disease, but these studies are also not robust. Azathioprine was demonstrated to reduce corticosteroid requirements in a randomized, placebo-controlled trial of generalized MG patients (Palace et al. 1998), and retrospective analyses support its efficacy in OM patients (Mertens et al. 1981; Matell 1987; Hohlfeld et al. 1988; Mantegazza et al. 1988). The clinician and the patient then need to consider immunosuppressant therapy, and here the evidence base relies on data from the generalized disease and expert opinion. For generalized MG, cyclosporine, tacrolimus, and mycophenolate mofetil have steroid sparing effects demonstrated in double-blind, placebo-

The analysis provides a focused review of clinical manifestations, diagnosis, and treatment of OM and highlights the significant limitations of the literature. Diagnosis of OM is generally straightforward, when the clinician thinks of the disorder. Confirmation of clinical diagnosis is challenging for OM. Serum AChR antibodies are found in only half of patients, and while the MuSK antibody is detected in about three percent of the generalized MG population, it is found only rarely among patients with isolated OM. Therefore the majority of patients lack detectable autoantibodies and confirmation of a neuromuscular transmission disorder relies on specialized, electrophysiological testing. Although expert opinion suggests that treatment is highly effective, significant knowledge gaps exist as to severity of treatment complications and over-all quality of life of patients with OM. Only through prospective trials or multi-center, rigorously constructed outcome databases will

patient's primary care physician to monitor for complications.

controlled or retrospective studies (Sanders and Evoli 2010).

improvements in treatment be achieved.

**5.4 Immunotherapy**

**6. Conclusion**

corticosteriods outweigh the complications of chronic corticosteroid use.

Thymectomy is not generally indicated of OM, but case series do support its use (Schumm et al. 1985; Roberts et al. 2001). Of course, OM patients with a thymoma should undergo tumor removal and co-incident removal of the remainder of the thymus.

#### **5.2 Acetylcholesterase inhibition**

AChE inhibitors are the first line of medical treatment for OM, and pyridostigmine is the most commonly used drug in the class. While AChE inhibitors are effective for ptosis, diplopia is of often resistant to treatment (Sommer et al. 1993; Sommer et al. 1997; Mehndiratta et al. 2011). In some patients, unilateral ptosis "unmasks" ocular misalignment producing the symptom of diplopia which may be more troublesome for the patient (Daroff and Benatar 2009). Patients presenting with both ptosis and diplopia tend to have an inferior response to pyridostigmine (Chirapapaisan N 2007), and many OM patients move on to corticosteroid treatment(Kupersmith and Ying 2005).

Pyridostigmine 30-60 mg three to four times per day are typical starting doses and may be increased to 90 to 120 mg every 3-4 hours per day, if symptoms respond and adverse effects are kept to a minimum. Complications are primarily related to muscarinic effects, in particular abdominal cramps, nausea, vomiting and diarrhea, which occur in at least a third of patients (Beekman et al. 1997). Atropine or glycopyrrolate may be used to limit muscarinic activity. AChE inhibitor treatment should be used with caution in patients with bradycardia and prostatic hypertrophy. Patients with MG treated with AChR inhibitors, who have reactive airway disease, may have worsening of respiratory function secondary increased respiratory secretions leading to a false conclusion that respiratory insufficiency is caused by myasthenic weakness. An open label prospective trial demonstrated improved quality of life with the sustained-release form of pyridostigmine, which requires less frequent administration (Sieb and Kohler 2010). However, in the author's experience, more reliable improvements in strength occur with the standard preparation. Cholinergic weakness is often discussed but probably does not occur in this era that patients move to immunotherapy and do not rely on extremely high doses of AChE inhibitors. However, if a clinician is concerned that cholinergic weakness is a cause of worse OM symptoms, the AChE inhibitor may be reduced.

#### **5.3 Corticosteroid treatment**

Most patients will not receive significant benefit from the non-pharmacological and AChE inhibitor treatments and will choose to proceed to immunosuppressive treatment (Kupersmith and Ying 2005). Prednisone is the most frequently used immunosuppressive treatment for OM, and unless corticosteroids are contraindicated due to comorbities, it is the first-line immunosuppressive for OM. Although this is based on retrospective analysis(Benatar and Kaminski 2007, Bhanushali et al. 2008).

Dosing regimens vary but typically, 10-20 mg once a day is started and increased by 5-10 mg every 3 days until visual symptoms are improved significantly, which usually occurs in the first few weeks of therapy (Kupersmith et al. 2003; Mee et al. 2003; Papapetropoulos et al. 2003). 60-80 mg per day is a maximum dose. At times mild double vision that does not impair function may persist and need to be tolerated. After symptom resolution is maintained for a month, a slow taper is instituted at a rate of 5-10 mg per day every 2 weeks until a dose of 20 mg every day is achieved and the dose reductions slowed further. Rapid tapers often lead to recurrence of symptoms, but even with gradual dose reductions a large percentage of patients will have symptom recurrence. Patients will need an increase in dose when symptoms recur. Most patients require maintenance doses for years, which should be the lowest possible to prevent recurrence of visual complaints. More than three-quarters of patients experience significant improvement (Evoli et al. 1988; Sommer et al. 1997; Tackenberg et al. 2001; Kupersmith and Ying 2005). To reduce corticosteroid complications every other day dosing of prednisone may be used. Patients should be instructed to take a single morning dose, which mimics the diurnal peak of endogenous corticosteroid. Patients need to be educated about steroid side effects, which include weight gain, glucose tolerance, hypertension, osteoporosis, insomnia, anxiety, depression, and the numerous other complications of prednisone. The neurologist or ophthalmologist should work with the patient's primary care physician to monitor for complications.

Based on retrospective analysis, corticosteroids may delay or prevent the progression of OM to generalized MG (Agius 2000; Kaminski and Daroff 2000; Kupersmith 2004). However, there has not been a randomized, controlled trial to assess whether steroids have a disease modifying effect (Gilbert et al. 2007; Gilbert and Savino 2007). Future studies should consider visual outcome and quality of life to determine whether the benefits of corticosteriods outweigh the complications of chronic corticosteroid use.

#### **5.4 Immunotherapy**

112 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Thymectomy is not generally indicated of OM, but case series do support its use (Schumm et al. 1985; Roberts et al. 2001). Of course, OM patients with a thymoma should undergo

AChE inhibitors are the first line of medical treatment for OM, and pyridostigmine is the most commonly used drug in the class. While AChE inhibitors are effective for ptosis, diplopia is of often resistant to treatment (Sommer et al. 1993; Sommer et al. 1997; Mehndiratta et al. 2011). In some patients, unilateral ptosis "unmasks" ocular misalignment producing the symptom of diplopia which may be more troublesome for the patient (Daroff and Benatar 2009). Patients presenting with both ptosis and diplopia tend to have an inferior response to pyridostigmine (Chirapapaisan N 2007), and many OM patients move on to

Pyridostigmine 30-60 mg three to four times per day are typical starting doses and may be increased to 90 to 120 mg every 3-4 hours per day, if symptoms respond and adverse effects are kept to a minimum. Complications are primarily related to muscarinic effects, in particular abdominal cramps, nausea, vomiting and diarrhea, which occur in at least a third of patients (Beekman et al. 1997). Atropine or glycopyrrolate may be used to limit muscarinic activity. AChE inhibitor treatment should be used with caution in patients with bradycardia and prostatic hypertrophy. Patients with MG treated with AChR inhibitors, who have reactive airway disease, may have worsening of respiratory function secondary increased respiratory secretions leading to a false conclusion that respiratory insufficiency is caused by myasthenic weakness. An open label prospective trial demonstrated improved quality of life with the sustained-release form of pyridostigmine, which requires less frequent administration (Sieb and Kohler 2010). However, in the author's experience, more reliable improvements in strength occur with the standard preparation. Cholinergic weakness is often discussed but probably does not occur in this era that patients move to immunotherapy and do not rely on extremely high doses of AChE inhibitors. However, if a clinician is concerned that cholinergic weakness is a cause of worse OM symptoms, the

Most patients will not receive significant benefit from the non-pharmacological and AChE inhibitor treatments and will choose to proceed to immunosuppressive treatment (Kupersmith and Ying 2005). Prednisone is the most frequently used immunosuppressive treatment for OM, and unless corticosteroids are contraindicated due to comorbities, it is the first-line immunosuppressive for OM. Although this is based on retrospective

Dosing regimens vary but typically, 10-20 mg once a day is started and increased by 5-10 mg every 3 days until visual symptoms are improved significantly, which usually occurs in the first few weeks of therapy (Kupersmith et al. 2003; Mee et al. 2003; Papapetropoulos et al. 2003). 60-80 mg per day is a maximum dose. At times mild double vision that does not impair function may persist and need to be tolerated. After symptom resolution is maintained for a month, a slow taper is instituted at a rate of 5-10 mg per day every 2 weeks until a dose of 20 mg every day is achieved and the dose reductions slowed further. Rapid tapers often lead to recurrence of symptoms, but even with gradual dose reductions a large

tumor removal and co-incident removal of the remainder of the thymus.

**5.2 Acetylcholesterase inhibition**

AChE inhibitor may be reduced.

**5.3 Corticosteroid treatment**

analysis(Benatar and Kaminski 2007, Bhanushali et al. 2008).

corticosteroid treatment(Kupersmith and Ying 2005).

Some patients will not respond to corticosteroids, have contraindications to their use, or have intolerable adverse effects necessitating use of other immunotherapies (Tackenberg et al. 2001). Assessment of efficacy for immunosuppressives specific to treatment for OM is extremely limited and is entirely based on retrospective investigation. Support for their use also derives from administration for the generalized disease, but these studies are also not robust. Azathioprine was demonstrated to reduce corticosteroid requirements in a randomized, placebo-controlled trial of generalized MG patients (Palace et al. 1998), and retrospective analyses support its efficacy in OM patients (Mertens et al. 1981; Matell 1987; Hohlfeld et al. 1988; Mantegazza et al. 1988). The clinician and the patient then need to consider immunosuppressant therapy, and here the evidence base relies on data from the generalized disease and expert opinion. For generalized MG, cyclosporine, tacrolimus, and mycophenolate mofetil have steroid sparing effects demonstrated in double-blind, placebocontrolled or retrospective studies (Sanders and Evoli 2010).


3.2.4. Control Variables

The following control variables are selected in this study: total assets (Size), fixed assets ratio (Far), Tobin's Q (TQ), return on net assets (Roe), the shareholding ratio of the largest shareholder (Top1), the gearing ratio (Debt), chairman and general manager (Dual), board size (Board), etc. The data were obtained from the CSMAR database. This study also controlled for year and industry fixed effects. Based on this, Table 2 shows the descriptive statistics of the main variables.

#### **Table 2.** Variable definitions.