Standard specifications of test engine.
--\x3e is obtained as
Substituting Eqs. (19) and (20) into (21), the spray tip velocity is represented as follows:
Before the transition timing, the spray tip is in steady state, so that the momentum flux and fuel mass flow rate integrated over the tip cross-sectional area \x3c!--(
where
Therefore, after substituting Eq. (6) into (9), the ūtip can be derived as
where
So far the spray tip penetration (Stip) can be obtained by
Eq. (12) cannot be solved as a continuous equation. Thus, the discrete method is used to calculate the spray tip penetration. The spray tip penetration at any time of t is obtained based on the spray tip penetration and the average velocity over the tip cross-section at the last time step (t – Δt) as Eq. (13)
And the average velocity over the tip cross-section at time t is obtained as
After the transition timing, the total momentum flux and fuel mass flow rate over the tip cross-section decelerate from the values of steady state because the information of fuel injection termination already arrived at the spray tip [18]. However, Eq. (9) is valid also for the period after the transition timing, which had been demonstrated in [31]. Thus, the same form as Eq. (10) are available for the average velocity over the tip cross-section, where
where ρtip, atr is calculated by Eq. (11), in which
where ttr is the transition timing.
\nTo obtain
where mf(t) is mass of fuel in the spray, t is the time from injection start, and Cd is a model constant. Finally, Xf,tip,atr is derived as
Whence the spray tip penetration after the transition timing is able to be obtained, and the method for solving Eq. (16) is same as that before transition timing.
\n\nAfter EOI, the mixture near the nozzle becomes very lean due to the termination of the fuel supply. Therefore, it is assumed that the part of the spray near the nozzle acts as ambient air zone and a spray tail exists. Knowing the position of the spray tail, the start time of the interaction with the subsequent spray can be determined.
\nIn this study, the spray tail position is determined as a cross-section of a spray where 10% of total fuel is contained up to the nozzle. It can be imagined that the tip of the spray formed by this 10% fuel equates the total spray tail. In other words, the tail penetration of the spray containing total injected fuel can be calculated by the tip penetration of the spray formed by an injection whose quantity is equal to 10% of total injection quantity. Figure 5 shows the examples of calculated tail penetrations compared to the tip penetrations for the injection quantity of 2.5 and 25 mg cases.
\nCalculated spray tip and tail penetrations for the injection quantity of 2.5 and 25 mg cases.
Another primary respect of simulation for diesel combustion with multiple-injection is to describe the interaction between the sprays from sequent injections. Figure 6 shows the spray-to-spray interaction, the interaction occurs after the arrival of the second spray tip at the first spray tail, and the entrainment from the first spray to the second spray is involved to represent the interaction.
\nThe entrainment behavior can be considered as that the spray entrains the ambient gas through the spray boundary that has a conical surface, therefore the entrainment rate can be represent as the product of air density, entrainment velocity over the spray boundary surface, and the area of spray boundary surface. After the second spray tip touches the first spray tail, the entrainment area of the second spray is divided into two parts by the first spray tail as shown in Figure 6. The ratio of the entrainment rate of these two parts (Re) can be obtained as Eq. (19) with assumptions as the air and the first spray have the same density and the entrainment velocity uniformly distribute over the spray boundary surface in the ambient air zone and the first spray zone, respectively:
where Aair and Aspray are the areas of the spray boundary surface in the ambient air zone and the first spray zone, respectively. Ce is a coefficient given to describe the difference between the entrainment velocity over the spray boundary surface in the ambient air zone and the first spray zone. Based on Eq. (19) and the total entrainment rate of the second spray, it is able to obtain the amount of the first spray mixture entrained into the second spray.
\nSpray interaction diagram.
Meanwhile, the swirl effects on the spray-to-spray interaction cannot be ignored. The swirl flow does not only decrease the spray penetration [32] but also deviates the spray path [23]. As that shown in Figure 7, the swirl effects causes the second spray tip to overtake the first spray tail and tip earlier than the case without swirl flow effects, and reduce the overlap region between the first and second sprays. Thus, based on the assumption that the entrainment rate is proportional to the spray surface area, the ratio (Re) of the entrainment rate from the ambient gas and that from the first spray have to be recalculated as follows:
Diagram of sprays interaction [34].
where Aupt and Ablt are the spray boundary surface areas up and below the first spray tail, respectively, and RSA is the ratio of surface area of the second spray in the first spray over Ablt.
\nTo calculate Aupt and Ablt, the reduction of spray penetration in injection direction by swirl flow are considered to determine the position at which the second spray tip touches the first spray tail. The ratio (RMJ) between the momentum from injected fuel (Mj) and total momentum in the spray, which includes the momentums from the injected fuel (Mj) and the entrained gas (Ms), is introduced as a factor for the penetration. The specific expressions are as follows:
where
To calculate RSA, the spray deflection by swirl flow was considered in a simple manner as shown in Figure 8. The shadow part expresses the overlap between the two sprays. The deviation angles θ1 and θ2, and the spray spreading angles α1 and α2 are assumed to have small values for this simplification. In this way, RSA is approximately proportional to the ratio of the angle between the first spray windward and the second spray leeward over the second spray spreading angle as in Eq. (24)
Simplification of sprays interaction with swirl flow effect [34].
The ratio (RMS) of the momentum from entrained gas over the total momentum in the spray, which is calculated by Eq. (25), is assumed to represent the degree of spray deflection instead of θ1 and θ2 in Eq. (24).
Adjusting the injection time earlier than top dead center (TDC) is often used to realize the PCCI or LTC, especially for the multiple-injection case in which the pilot injection time is usually advanced to the middle even at the early stage of compression stroke. The early injection timing makes the spray flow into the squish region and impinges on the cylinder liner or piston top as shown in Figure 9. Due to the low temperature of the walls and/or the adherence of fuel on the piston top surface, oxidation reaction and mixing in the mixture are attenuated [35]. To involve such effects in the stochastic combustion model, the reduction of fuel-air turbulent mixing rate was considered according to the volume ratio of the spray flowed into the squish area and total spray. The temperature effect mentioned above was not considered; however, the overall oxidation reaction rate is lowered as a result of reduced mixing rate.
\nWall impingement diagram.
As shown in Figure 9, if the spray tip cross-section impinges on the bowl lip edge, the spray can be divided into two parts, squish part and bowl part. Thus the volume ratio between squish part and incremental spray (Rsq, inc) can be calculated as follows:
where Aup and Abl are the areas of the cross-sectional area at impinging timing over and below the bowl lip edge, respectively, and the C(θ) is a function of the angle between the spray central line and cylinder head, and it is used to describe the ratio between spray spreading velocity in squish region and bowl region. This function is selected as cot θ in this study, because it represents the ratio of the horizontal and vertical components of average spray tip velocity when the piston top is treated as a horizontal area. Sequentially, the volume ratio of spray flowed into squish region and total spray (Rsq) can be obtained as follows
where tim is the impinging timing and Vspray is the total spray volume. And the stochastic collision frequency (ω) that represents the turbulent mixing rate is calculated as follows:
where Cm is a constant, ω0 is the collision frequency of free spray, and Gj is the total turbulence energy generated by injection. Gj is used with minus power (x), because the larger turbulence energy generated by injection causes the stronger mixing (larger ω). Cm and x were selected as 6.2 and –0.2 respectively, which are calibrated by experimental heat release rates under different injection time cases.
\nFigure 10 shows abstracted diagram of the situation of spray impinging on the wall in the cylinder. The upper spray represents the initial stage of wall impingement. In this stage, it is reasonable to consider that the air entrainment is enhanced because the surface area of spray is enlarged by wall impingement [36–38]. Thus, to improve the stochastic combustion model, a constant (CETRM) is given to multiply the entrainment rate of free spray after the wall impinging. In addition, the interaction between adjacent sprays is an important factor on air entrainment decrease, the primary reason can be considered that the adjacent sprays overlap after wall impingement as shown in Figure 10 (below sprays) decreases the entrainment area of spray, thereby the entrainment rate is suppressed. In order to involve these effects in a simple way, the ratio of the total spray volume and the chamber volume was used to represent the intensity of the interaction between adjacent sprays, and the interaction effect on entrainment rate is introduced as follows:
where \x3c!--
CETRM and Cvr are set as 1.5 and 0.8, respectively, based on the comparison between calculated and experimental heat release rates.
\nSpray propagation along the wall.
Based on the assumption that most of the NOx is NO, the production of NO during combustion process is computed by the extended Zeldovich mechanism [39]. Meanwhile, the NO normally produces at a high rate in the mixture with equivalence ratio around 1.0 accompanying with high temperature. Thus, the NO concentration is estimated in the fluid elements whose temperature is over 1200 K with the equilibrium species including C, CO, CO2, O2, O, OH, H2, H, H2O, N2, and NO.
\nThe soot model refers to the Moss’s soot model [40]. Moss’s soot model is a semi-empirical soot model derived based on laminar diffusion flame. The soot particles inception and coagulation are considered for the calculation of soot particles number density, and the soot particles surface growth and oxidation are calculated to obtain the soot volume fraction. The soot oxidation rates per unit area by O2 and hydroxyl radical (OH) are introduced to calculate the soot oxidation rate in this model. The soot oxidation rate per unit area by O2 (RSO) is calculated using the Nagle and Strickland-Constable (NSC) model [41]. The soot oxidation rate per unit area by OH (RSOH) is considered by referring Neoh’s equation [42].
\nThe test engine is a water-cooled single-cylinder four-stroke-cycle direct-injection diesel engine equipped common-rail injection system. The standard specifications are given in Table 1.
\nEngine type | \nSingle-cylinder, DI-diesel engine | \n
Bore × Stroke | \n85 mm × 96.9 mm | \n
Displacement | \n550 cc | \n
Compression ratio | \n16.3 | \n
Combustion chamber | \nReentrant type (51.6 cavity) | \n
Injection system | \nCommon-rail system 0.125 mm × 7 holes nozzle | \n
Standard specifications of test engine.
All of the experiments were performed at thermally steady states of the engine at a fixed speed of 1500 rpm, an inlet coolant temperature of 80°C, and a lubricating oil temperature of 80°C. The intake pressure was 0.1 MPa and the intake temperature was 35°C. Exhaust back pressure valve was fully open. The fuel was JIS No. 2 diesel fuel (density at 15°C = 820.2 kg/m3 and cetane index = 54.7). The averaged in-cylinder pressure of 50 cycles was used to calculate the heat release rate, which was measured using a piezoelectric pressure transducer (Kistler 6052A).
\nWith the aim for validating the simulation of combustion with multistage injection, at first, the pilot/main two-stage injection strategies were conducted in experiment and calculation, and the calculation ran from intake valve closure (IVC) of –145°ATDC to exhaust valve open (EVO) of 125°ATDC. Since the start of main injection is normally set near TDC in the pilot/main injection strategy, the main injection timing (θmain) was fixed at 1°ATDC, and pilot injection timing and quantity were varied. And the engine operating condition was selected as high load, for which the indicated mean effective pressure (IMEP) was set to 1.01 MPa, in order to observe the variation of combustion phases including premixed combustion and mixing-controlled combustion affected by pilot injection condition. The main experimental conditions are listed in Table 2.
\nInjection pressure | \n125 MPa | \n
Total injection quantity | \n32 mm3 per cycle | \n
Pilot injection quantity (qfpilot) | \n2, 4, and 6 mm3 per cycle | \n
Pilot injection timing (spilot) | \n–9, –19, and –24°ATDC | \n
Main injection timing | \n1°ATDC | \n
EGR ratio | \n20% | \n
Swirl ratio | \n2.0 | \n
Experimental conditions.
To valid the combustion model, the in-cylinder pressures and the heat release rates were calculated and compared to the experimental data at first. Figures 11–13 show the in-cylinder pressures and heat release rates for different pilot injection timings and quantities. The simulation results obtain the similar levels of pressures and heat release rates to those of the experiments. It is also observed that the model is able to capture the tendencies of the pressure and heat release rate when varying the pilot injection timing and injection quantity.
\nEffects of pilot injection quantity on the in-cylinder pressure and the heat release rate (θpilot = –9°ATDC).
Effects of pilot injection quantity on the in-cylinder pressure and the heat release rate (θpilot = –19°ATDC).
Effects of pilot injection quantity on the in-cylinder pressure and the heat release rate (θpilot = –24°ATDC).
Based on the good agreement in the pressures and the heat release rates, the NOx and soot emissions were calculated. Figure 14 shows the NOx (left) and soot (right) emissions against the pilot injection timing. The results reveal that the NOx calculation obtains the similar emission level and the variation caused by pilot injection conditions changing with the measured data. Regarding to the soot emission, the soot emissions level obtained by the model is comparable with the measured data, and the calculated soot emissions are able to reproduce the increase with the increase in pilot injection quantity at fixed pilot injection timings, which is observed in the experimental data. Although the tendency of soot emissions variation with pilot injection timing retarded does not completely coincide with that of every experiment with different pilot injection quantity, the general tendency can be captured correctly.
\nNOx and soot emissions.
In this study, a stochastic combustion model was introduced to develop a phenomenological combustion model for modern diesel engines. In order to be able to describe the combustion process of advanced combustion mode, the spray propagations after EOI, spray-to-spray interaction, swirl effects, and wall impingement effects were modeled based on their physical phenomena in appropriate ways for the stochastic combustion model. Then, the developed combustion model was validated based on the experimental data from a single-cylinder diesel engine with pilot/main two-stage injection. The results revealed that the model is able to accurately predict the combustion of the diesel engine with pilot/main two-stage injection, and reasonable prediction of NOx and soot emissions can be obtained by this model. Specific conclusions are as follows:
(1) A zero-dimensional spray propagation model was derived. The spray model is able to predict the spray evolution including spray tip penetration and overall air entrainment after EOI. It is capable to catch the spray propagation tendency after EOI as that well recognized by the fundamental study. Thus, based on introducing this model, the accuracy of the combustion model can be improved especially for the short injection duration case in which the ignition is later than the EOI. As for the multiple-injection case, the thermodynamic states of the gas in the cylinder before the later injection start can be predict more realistically.
(2) Presumed spray tail was proposed for zero-dimensional spray model, which allows to take account of the fast dilution of the mixture near the injector tip after EOI, which resulted by the terminated fuel supply and increased air entrainment rate near the injector tip after EOI. And thanks to the presumed spray tail, the interaction between sprays from sequent injections was formulated by the rate of entrainment into the later spray from the former spray and/or the surrounding gas. Meanwhile, spray deflection by swirl flow cannot be neglected when imitating the interaction between sprays from sequent injection. And the interaction with swirl flow effect was described based on a simple geometrical consideration and formulated using the momentum from injected fuel and entrained gas. In this way, the stochastic combustion model can be used for simulation of combustion with multistage injection.
(3) To consider the wall impingement effect in early injection timing case, after wall impinging, the volume ratio of the spray flowed into the squish area, and total spray was introduced to reduce the fuel-air mixing rate that can involve the combustion chamber shape effects in the phenomenological combustion model.
(4) Air entrainment rate enhancement caused by wall impingement was considered by a factor with air entrainment rate of free spray during initial stage of wall impingement. And the reduction of main spray entrainment rate by interaction between adjacent sprays was formulated by the ratio between spray volume and chamber volume to balance the effect of enhanced air entrainment rate in the late combustion period. According to the results, effects of wall impingement and adjacent spray interactions on the entrainment rate are helpful to well predict the heat release rate in initial and late combustion periods, respectively.
The experiments and modeling work presented here had been performed in Combustion and Power Engineering Laboratory at Kyoto University. The research is supported by National Natural Science Foundation of China (Grant No. 51509051) and Natural Science Foundation of Heilongjiang Province of China (Grant No. LC2015017).
\nChronic obstructive pulmonary disease (COPD) is among the five leading causes of death in developed world [1]. Prevalence of COPD is constantly increasing. COPD has a high impact on patients’ wellbeing, healthcare utilization, and mortality [2] and causes a substantial and increasing economic and social burden [3, 4]. Cigarette smoking is clearly the predominant cause but other environmental agents including biomass fuel and air pollution may play a role as well. Common symptoms of COPD patients are chronic and progressive dyspnea, cough, and sputum production. These symptoms can be disabling and lead to activity limitation and ultimately inability to work and take care of themselves [5]. This vicious circle of inactivity that begins with breathlessness is because of peripheral muscle dysfunction [6], and dynamic hyperinflation [7].
\nFor several decades, treatment of COPD has been focused on smoking cessation, and pharmacological but with ever-increasing literature, intense exercise programs like pulmonary rehabilitation (PR) have become an integral part of management of COPD [8]. PR has been shown to be the most effective non-pharmacological intervention for improving health status in COPD patients and has become a standard of care for these patients [2]. PR and pharmacological therapy are not competitive but rather, must work closely together, if they are to result in a more successful outcome [9].
\nDespite increasing awareness on positive impact of rehabilitation in COPD, it remains underutilized in most countries. Lack of understanding on the benefits of a PR program, in addition to the incremental cost to the management, has hindered the widespread adoption of comprehensive PR for COPD patients [9]. This chapter aims at highlighting the impact of PR on patients with COPD, focusing on the clinical usefulness of PR. We also hope to stimulate primary care and pulmonary physicians to use PR more often.
\nPhysical therapy has been incorporated into the treatment of pulmonary patients as far back as the First World War. Winifred Linton, a British nurse, first felt the need for physical therapy while treating traumatic respiratory complications during the war. Following the war, she entered physical therapy training and began to teach localized breathing exercises to other physical therapists (PTs) and surgeons at the Royal Brompton Hospital in London. A few physical therapists in the United States were instructed in airway clearance techniques and began to use and teach them to patients during the polio epidemic of the 1940s [10, 11]. Rehabilitation programs for patients with COPD have existed for more than three decades and were incorporated into ATS official statement in 1981 [12]. Comprehensive and multidisciplinary approach to the pulmonary rehabilitation programs have remained the key to its success over several years. It involves a team effort from physical therapist, respiratory therapist, nurses, physician and other support staff.
\nPulmonary rehabilitation has been defined as a comprehensive program which is individual patient focused and includes exercise training, education, and behavior change. It has been found to help improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors [13].
\nPulmonary rehabilitation has demonstrated physiological, symptom reducing, psychosocial, and health economic benefits in multiple outcome areas for patients with chronic respiratory diseases [14]. PR is appropriate for most patients with COPD. Improved functional exercise capacity and health-related quality of life has been demonstrated across all grades of COPD severity, although the evidence is strong in patients with moderate to severe disease [15].
\nBeside respiratory symptoms of dyspnea, COPD has been established to have extra-pulmonary manifestations. Some on them involve skeletal muscle dysfunction which results from physical inactivity and systemic inflammation in addition to hypoxemia, undernutrition, oxidative stress and systemic corticosteroid [16, 17].
\nPeripheral muscle dysfunction seen in COPD patients is a result of multitude of pathophysiological changes occurring in the skeletal muscles. Skeletal muscles in COPD patient have decreased oxidative capacity that can lead to early lactic academia [18, 19, 20], decreased muscle fiber volume [21], redistribution of the muscle fiber type (from type 1 to type 2 fibers) [21, 22, 23], and abnormal muscle fiber capillarization [23]. These changes in the structure and functioning of the skeletal muscles can lead to higher concentration of lactate for a given work. This in turn can lead to increased ventilation, resulting in dynamic hyperinflation and overall increased ventilator burden. With muscle dysfunction there is a limitation in the activity and promotion of a sedentary lifestyle. A sedentary lifestyle inevitably leads to social isolation, depression and physical deconditioning. Exacerbations of COPD also promote the reduction of exercise performance, dyspnea, and the loss of Health-related quality of life (HRQoL) [24].
\nPR has no direct impact on lung mechanics or gas exchange [25]. Rather, it optimizes the function of other body systems so that the effect of lung dysfunction is minimized [26]. A comprehensive PR program can help COPD patients gradually improving muscle function by changing muscle biochemical structure. This leads to improved tolerance for higher work load in the patients [27]. PR additionally reduces the central perception of dyspnea and dynamic hyperinflation [28].
\nA usual pulmonary rehabilitation program can range anywhere from 6 weeks to 12 weeks at various centers which incorporate aerobic exercise, education, muscle strengthening etc. Usually patients undergo supervised training 2–3 times a week, for 30–60 minutes in each session. This could include any regimen for endurance training, interval training, resistance/strength training, walking exercises, flexibility, inspiratory muscle training and/or neuromuscular electrical stimulation. The interventions are individualized to maximize personal functional gains.
\nThere are several benefits of PR not limited to improvement in symptoms like dyspnea, exercise tolerance and overall health status in stable patients.
\nPR results in reduction in symptoms of dyspnea and leg discomfort. Patients notice improved limb muscle strength and endurance. Most patients also experience improved functional capacity with more independence in activities of daily living (ADLs) [29]. In a Cochrane review [30] including 23 randomized controlled trials, PR was found to relieve dyspnea, and fatigue, improved emotional function and patient’s sense of control over their condition. All these improvements were large and statistically significant.
\nThere has been increasing interest in physical activity, as inactivity has been linked with reduced survival, poorer quality of life and increased healthcare utilization [31]. In the same Cochrane review as above [30], patients were noted to have improved exercise capacity. Other studies from Griffith’s et al. and Singh et al. have suggested similar findings [32, 33].
\nPR has also been found to reduce unscheduled healthcare visits, COPD exacerbation and hospitalization in some literature [34]. Rubi et al. reported reduction in COPD exacerbation, hospitalization and days of hospitalization in 82 consecutive patients [35]. In fact, there is some literature to suggest reduced hospitalization in patients participating in PR programs immediately after acute exacerbation of COPD (AECOPD) beginning within 1 week of discharge [36].
\nAnxiety and depression affect significantly in COPD patients leading to worse patient centered outcomes. Tselebis et al. conducted study in 101 consecutive patients and noted that psychological morbidity was improved with participation in PR program irrespective of severity of the disease (COPD) [37]. This was confirmed in a meta-analysis of six RCTs which indicated that pulmonary rehabilitation was more effective than standard care for the reduction of anxiety and depression [38].
\nHRQoL was noted to be significantly improved in patients with COPD participating in PR as well [34, 39]. The St. Georges Respiratory Questionnaire Scores were used in a meta-analysis, which showed significant improvement in HRQoL following pulmonary rehabilitation [40]. An early RCT compared pulmonary rehabilitation with education alone and demonstrated that self-efficacy improved in the intervention group [41].
\nCOPD patients have been known to have improved mortality with cessation of smoking. There is some signal that an association exists between completion of PR and survival based on a retrospective analysis involving 1515 patients [42]. But a systematic review conducted of two randomized control trials showed significant survival benefit at 1 year in one trial but no significant benefit with another study at end of 3 years. Neither of the study was powered to really derive the desired outcome [43].
\nPatients with chronic lung condition who have symptomatic shortness of breath limiting their physical activity despite optimal medical management should be considered for pulmonary rehabilitation [44]. Patients with chronic diseases other than lung such as heart failure, musculoskeletal disease have the same benefit form pulmonary rehabilitation as patients with disabling lung conditions like chronic obstructive pulmonary disease, restrictive lung disease, and pulmonary hypertension. Pulmonary rehabilitation can markedly change the course of the disease if provided at an earlier stage of disease. This is due to improved exercise tolerance and physical activity, reduced exacerbations and improved self-efficacy and behavior change after pulmonary rehabilitation. [45]
\nOne of the most important indicator for referral to pulmonary rehabilitation is based on the modified Medical Research Council Breathlessness (mMRC) score (see Table 1) [46]. The mMRC scale is a 0–4 grade scale used to establish levels of perceived respiratory disability. It allows patients to indicate the extent to which their breathlessness affects their mobility [45, 46].
\nGrade | \nLevel of breathlessness with the activities | \n
---|---|
0 | \nNo shortness of breath except on strenuous exercise | \n
1 | \nShort of breath when walking on an incline | \n
2 | \nWalks slower than contemporaries on a level ground because of shortness of breath or has to stop due to breathlessness when walking up at own pace | \n
3 | \nStops for breath when walking 100 m or after a few minutes on level ground | \n
4 | \nToo short of breath to leave the house, or short of breath when dressing and undressing | \n
The modified Medical Research Council Breathlessness (mMRC) score.
It has been strongly recommended that patients with an mMRC dyspnea score of 2–4 who are functionally limited by breathlessness should be referred for pulmonary rehabilitation. However, benefits of pulmonary rehabilitation have also been seen in patients with an mMRC dyspnea score of 1 who are functionally limited by breathlessness. Patients with COPD who have an mMRC score of 4 achieve similar benefits from the pulmonary rehabilitation as those with a lower breathlessness score [47].
\nOther frequent indications for referral to a pulmonary rehabilitation program include poor functional status, physical deconditioning, chronic fatigue, poor health-related quality of life and difficulty performing activities of daily living. Patients who are requiring increased use of medical resources due to frequent exacerbations, hospitalizations and emergency room visits also benefit from pulmonary rehabilitation.
\nCandidates for lung volume reduction surgery for severe emphysema or for lung transplantation are also good candidates for PR [48]. Patients with COPD have shown improvements following a pulmonary rehabilitation program irrespective of their age or gender [49, 50, 51].
\nLevel of functional impairment [47, 52, 53] or disease severity does not affect the benefits seen in COPD patients with pulmonary rehabilitation program [54, 55]. A program of PR may be proposed in stable COPD as well as immediately after COPD exacerbation [56].
\nThere are very few exclusion criteria for a referral to pulmonary rehabilitation, which includes patients with the following conditions [45, 46]:
Unstable cardiovascular disease, uncontrolled diabetes and an ongoing orthopedic illness that will refrain patient from exercising.
Inability to do exercise safely because of any other medical illness like severe arthritis, severe peripheral vascular disease.
Untreated psychiatric illness and cognitive impairment which makes it hard for patients to follow directions are other reasons for not referring a patient to pulmonary rehabilitation.
Lack of motivation is another exclusion criterion for pulmonary rehabilitation.
Adherence to pulmonary rehabilitation program is critical to see the ongoing benefits from the program. However, non- adherence and high dropout rate of 20–30% is reported in the studies listing predictive factors of non-adherence to pulmonary rehabilitation. These factors include [52, 53, 57, 58]:
Even though current smokers obtain the same benefits from pulmonary rehabilitation, smokers generally have poor adherence to pulmonary rehab than ex-smokers. Active smoking status is not an absolute contraindication for pulmonary rehabilitation. Patients are encouraged to undergo smoking cessation prior to pulmonary rehabilitation.
Depression and social isolation.
Lower quadriceps strength.
COPD patients with higher mMRC score and frequent exacerbations.
Long commute to pulmonary rehabilitation and lack of transport.
Cost of pulmonary rehabilitation.
Every patient referred for pulmonary rehabilitation should be thoroughly evaluated prior to initiation of the program. Majority of the patients have a regular pulmonary physician managing the lung disease. As a part of the management, pulmonary physicians refer the patient for pulmonary rehabilitation to supplement the pharmacological treatment. These patients when present to the pulmonary rehabilitation have already undergone an evaluation of symptoms and physical examination. Regardless, it is a good practice to perform a thorough evaluation of patient’s medical problems, laboratory results, social habits and specific medications. This should be accompanied by a comprehensive physical examination with estimation of patient’s functional capacity. In most of the pulmonary rehabilitation program, this assessment is performed by the physical therapists. If a pulmonologist is an integral part of the program, the physician can do this work up.
\nPrior to initiation of the pulmonary rehabilitation program, a careful appraisal of patient’s pulmonary disease and current severity should be done. For COPD patients this will include the duration of their symptoms, current symptomatology, mMRC score [46], smoking history, pulmonary function testing, arterial blood gas analysis, inhaler therapy, oxygen supplementation and non-invasive ventilation prescription. It is imperative that a special attention should be paid to patient’s co morbidities. This is essential as several other medical problems may have impact on patient’s disease course and exercise capacity. These may include obesity, OSA, diabetes, cardiovascular co morbidities, hypertension, osteoarthritis, pulmonary hypertension, peripheral vascular disease and malignancy.
\nA detailed pre rehab assessment enables the physical therapist to devise an individualized treatment plan for the patients. This strategy is particularly helpful for patients with advanced disease, low exercise tolerance, special healthcare needs such as high oxygen requirements, pacemaker or defibrillators, walkers and cane. Information gathered at the beginning of the program will help set realistic individualized goals and alert the provider regarding the possibility of adverse effects.
\nPhysical examination at the beginning of the pulmonary rehabilitation program is centered on measurements of patient’s functional status and capacity to handle additional physical stress. Most relevant for COPD patients will be an examination of muscle wasting, joint mobility, postural deformities, and cardio-respiratory examination. Results of this examination allows physical therapist to gauge individual patient’s tolerance and potential areas of improvement.
\nAn important component of physical examination is nutritional assessment. This commonly includes measurement of weight, height and BMI. Both being underweight and overweight in a COPD patient can be detrimental. Excess weight can lead to extrinsic restriction on lung capacity as well as increased work of breathing. Weight loss and muscle wasting is a poor prognostic factor in COPD patients [59, 60, 61].
\nPertinent respiratory examination in patients with COPD is directed at ability of the patients to clear their respiratory secretions, use of accessory muscles of respiration, breathing pattern, adventitious sounds on auscultation such as wheezing and crepitation. A knowledge of patients’ respiratory status will help develop an educational plan regarding self-management, medication compliance and respiratory muscle training.
\nReduced functional capacity due to physical deconditioning is widespread in COPD patients. This is multifactorial with poor nutritional status, systemic inflammation, cardiovascular comorbidities, postural deformities and osteoporosis [62] Interviewing the patient to ascertain their capacity to perform ADLs, sustained exercise and risk of falls is essential. Several questionnaires have also been used to objectively measure individual patient’s baseline functionality. A few examples include: the Functional Independence Measure (FIM), the Assessment of Motor and Process Skills (AMPS), and a Functional Capacity Evaluation (FCE) [63].
\nApart from questionnaire, various exercise tests can be used to gauge individual patient’s functional capacity. These exercise tests can be done as field walking tests, on bicycle ergometer or on treadmill. In most hospital, simple walk testing can be cost effective and practical. Walk tests are considered more reflective of daily functionality of a COPD patient. Some of the commonly employed walk tests include the 6-minute walk test (6MWT) and the incremental shuttle walk testing. Standardized protocols have been established for performing the 6MWT. If done as per the set protocol, this walk test is highly reproducible and reliable test for both diagnostic and prognostic purposes. In this test, patient walk back and forth on a 30-m distance marked hallway at their own pace for 6 minutes. During the test, distance walked, vital signs, oxygen desaturation, development of dyspnea using a visual analog scale is measured [64]. The incremental shuttle walk test is performed on a 10 m marked course. It is a paced walk test to assess symptom limited maximal exercise capacity. Test is continued until patient develops symptoms of dyspnea or for 20 minutes, whichever occurs first. This is a valid and popular testing in various resource limited clinical settings [45].
\nIf in addition to the functional limitation specific problems are identified by the physical therapists, various other tests may need to be performed. These tests address the muscle weakness, gait disturbances, and include balance testing and sit-to-stand tests [65].
\nAfter an initial assessment, patient is enrolled into a pulmonary rehabilitation program. The basic aim of such a program in any COPD patient is to assist them in performing essential daily activities with independence. Independence comes from reduction in dyspnea and fatigue. COPD patient are inadvertently caught in a downward spiral where dyspnea is leading to inactivity, which in turn leads to physical deconditioning and decreased capacity to handle day-to-day stress. To save the patient from this downward spiral a pulmonary rehabilitation program focuses on improving the cardiorespiratory endurance, muscle strength, body flexibility and respiratory muscle training. With an individualized patient’s clinical analysis and examination, a specific therapy plan can be built for each patient. This plan is intended to establish patient specific goals and focus on areas of functional limitation, which need to improve to achieve those goals. As the COPD patients undergo pulmonary rehabilitation, improvement in their physical deconditioning and exercise capacity needs to be measured and documented. This is achieved by using a variety of parameters, such as quantity of exercise performed or improvement in perception of dyspnea, symptoms, heart rate during exertion. Any changes seen in these parameters will be suggestive of patient’s improved capacity to handle the physical stress. As discussed earlier in the chapter walk tests and questionnaires can provide an objective measure of functional improvement for COPD patients undergoing pulmonary rehabilitation.
\nPhysical exercise training in COPD patients can be delivered in two forms: Continuous high intensity aerobic endurance training or an interval training, which alternates high intensity aerobics with low intensity exercises [66]. Continuous high intensity regimen of endurance training can be administered with constant load or incremental load. It has been shown that high intensity aerobic training (70–80% of peak work rate), will result in maximal improvement in physical fitness by increasing oxygen consumption, delaying anaerobic threshold and decreasing heart rate for a given exercise rate [27, 62, 67, 68, 69].
\nIn patients with advanced COPD and persistent dyspnea a high intensity endurance training is difficult to sustain. These patients can be provided with interval endurance training. In this approach, high intensity aerobic training in short bouts (30–180 s) is alternated with low intensity exercises (leading to a subjective experience of exertion between 4 and 6 on the modified Borg scale) or rest [70, 71, 72, 73, 74].
\nEven though there may be less appreciable gains in aerobic parameters, this training approach has proven to be effective in improving exercise endurance in COPD patients [42, 75]. Interval endurance training leads to lesser degree of pulmonary hyperinflation allowing patients to exercise longer without excessive dyspnea. COPD patients may more easily adapt a lower intensity exercise regimen in their daily life. The choice of regimen is ultimately based on both therapist and patient preference.
\nEndurance training is delivered using various modalities including walking (treadmill or supported ground walking with walker or wheelchair), cycling, rowing, and swimming or modified aerobic dancing. It is recommended to provide this training 3–5 times per week at an intensity aimed at a Borg Dyspnea score of 4–6 (moderate level of exercise) [26, 44, 48, 67, 69, 76, 77, 78, 79]. Exercise sessions can last from 30 to 120 minutes, with at least 30 minutes of continuous aerobic activity, based on each patient’s capacity [26, 46, 79, 80]. General recommendation for the frequency of pulmonary rehabilitation is two supervised exercise sessions a week with third unsupervised session based on the available resources [44, 81, 82]. A minimum of 12 exercise sessions or 4 weeks of rehabilitation program is essential to achieve any improvement in physical fitness. Program length can be increased up to 72 weeks if patient is inclined and insurance coverage is favorable [48, 83, 84]. While shorter (6–8 weeks) pulmonary rehabilitation programs are more cost effective and widespread, longer duration programs have shown sustained beneficial effects. This is mostly due to fact that longer duration programs not only lead to physiological changes but also behavioral changes [85].
\nMore specific for COPD patients it is recommended to check oxyhemoglobin saturation both prior to the start of the exercise and at peak work rate. This will not only help to ascertain the need for oxygen supplementation but also guide both therapist and the patient to know appropriate level to use with different intensity of work. Similarly, a careful attention on patient’s bronchodilator therapy, both long acting and short acting, is essential during the program. Patients may require administration of short acting bronchodilator at the beginning of the exercises or during the workout. For a successful outcome of endurance training it is important that patient gets trained on similar oxygen delivery device that they use at home and are on optimal management of COPD. A stable respiratory function will allow the patients to tolerate higher intensity workout for longer duration.
\nApart from improvement in endurance, COPD patients benefit from increase in their muscle strength [26, 83, 86, 87] . Increased muscle strength provides the patients with an ability to handle the ADLs better, improves their gait and reduce fall risk, thereby making them more independent [88]. A recent meta-analysis investigating different methods of PR in COPD showed greater improvement in HRQoL by adding strength training than endurance training alone [89]. Physiologically improving muscle strength in COPD patients can lead to increase in physical endurance, 6-minute walk distance and maximum oxygen consumption [90, 91]. Strength training is most beneficial if directed at muscles involved in functional living. This involves training muscles in upper and lower extremities as well as the trunk.
\nIt has been well proven that exercise training of the lower extremities leads to significant improvement in ambulatory stamina in COPD patients [42, 67, 92, 93, 94]. This is because lower extremities suffer most from disease-related muscular dystrophy in COPD patients. Additionally increasing lower extremity strength can reduce falls and maintain bone mineral density in COPD patients [45]. General recommendation to improve lower extremity strength is to provide resistance training with 2–4 sets of 10–15 repetitions of each exercise, for 2–3 days per week. Selection of weight for this type of resistance training workout is individualized based on patient’s capacity. Increment in the weight is done gradually once patient is able to accomplish all sets of exercise with a prescribed weight [45]. Lower extremity training can be achieved using walking, bicycling with incremental loads, stair climbing, swimming, weight machines or elastic bands. Choice is driven by available resources at the training site.
\nPatients suffering from COPD who have hyperinflation and flattened diaphragm have limitation in using their upper extremities to perform ADLs. Elevation of arms can result in increased ventilatory and metabolic demands in COPD patients with low respiratory reserves. This is thought to be because some of the upper extremity muscles also serve as accessory muscles of respiration [95, 96, 97]. Majority of the published literature on pulmonary rehabilitation suggests beneficial effect of upper extremity training in COPD patients. Some of the observed benefits of this training include improved upper extremity strength, which is task specific, decreased ventilatory demands and more independence in performing ADLs. Despite these observed benefits, optimal prescription of upper extremity training remains unclear.
\nPhysical therapists have to be mindful that in training the upper extremities, COPD patients may have elevated ventilatory work, asynchronous breathing and more dyspnea for the level of work. It is prudent to start with low resistance and frequent repetitions before gradually increasing the weight [81]. Upper extremity and trunk muscle strength training is achieved by using light weights (dumbbells, elastic bands), weight machines for stronger patients, rowing machines etc. Several of these instruments can also provide aerobic exercise training thereby improving both strength and endurance in the upper extremities.
\nPhysical therapists may provide training of upper and lower extremities on alternate days to improve patient tolerance. Progressive improvement in muscle strength is documented using standardized lifting tests, incremental resistive load tolerated by the patient and increased capacity in performing ADLs efficiently [86].
\nMany COPD patients suffer from modification in the structure of their chest wall due to hyperinflation, hypertrophy of the accessory respiratory muscles and physical inactivity. This further leads to changes in the posture and reduced mobility. To prevent this from happening, COPD patients undergo flexibility training as a part of the pulmonary rehabilitation program.
\nFlexibility exercises lead to improved mobility by increasing joint range of motion, reducing joint stiffness, better posture and increment in vital capacity [45]. Gentle stretching exercises with full body movements, coordinated with breathing techniques are appropriate for COPD patients [65, 98, 99].
\nThis kind of workout teaches the patient the influence of body movements on respiration. Since these exercises are done at a slower pace without any resistive loads, they can be used during warm up or cool down periods of the program. Limited research has been done on adequate duration and intensity of stretching exercises. General recommendation are to perform stretching of major muscle groups in the upper and lower extremities 2–3 days per week at the minimum [100]. Benefits of this training can be measured by documenting reduction in subjective perception of stiffness, reduced incidence of back pain and joint injuries.
\nTo provide a holistic care, every pulmonary rehabilitation program should incorporate patient education. It has been well proven that COPD patients who are well aware about the nature of their disease, its management and long-term implications are able to cope with both the disease and treatment better [101]. Education about the disease empowers the COPD patients to better recognize their symptoms, make lifestyle changes and get involved in the management of the disease. This leads to increased motivation to participate in pulmonary rehabilitation and adhere to the exercise regimen.
\nAt the beginning of the rehabilitation program, individual educational needs of each patient are identified. This is continuously reassessed while the patients are undergoing the rehabilitation program. Instead of a didactic teaching, a patient centered and self-management teaching approach focusing on lifelong behavioral changes are adopted these days [45]. Specifically for COPD patients, a collaborative self-management plan which helps them in an identification of symptoms of onset of an exacerbation, make treatment modification and to communicate early with a healthcare provider, is highly beneficial in the long run [102]. Patient education runs alongside the exercise training. It is meant to supplement the knowledge gaps and instill confidence in the principles of ongoing training. Various topics regarding disease and its management are covered with utilization of the expertise of various specialists.
\nExacerbation of COPD is an additional burden on patient’s already weakened functional capacity. It leads to hospitalization, further inactivity, deterioration of lung capacity and mortality. It may also disrupt any advances the patient may have made in improving their exercise capacity and muscle strength [45, 46]. There is an emerging data suggesting that there is benefit in instituting and/or continuing with pulmonary rehabilitation during hospital admission or within a month of hospital discharge. An early initiation of pulmonary rehabilitation reduces risk of re-hospitalization and improves overall symptoms without any adverse effects [103].
\nA pulmonary rehabilitation program incorporating occupational therapy is important in COPD patients [104, 105]. Occupational therapy assists COPD patients with development of specific strategies to perform ADLs with least expenditure of energy [106]. With conservation of energy expenditure, there is an improvement in subjective perception of breathlessness, increased efficiency in performing daily basic activities, elevated sense of control and better social engagement [104, 105, 106, 107]. Occupational therapy skills even though simple in principle, require a learning process, which is achieved through a multidisciplinary rehabilitation program. There is an ever-increasing evidence that improvement in occupation performance of COPD patients lead to a holistic improvement in their health [108]. Occupational therapist can also instruct COPD patient to use wheeled walking aids, which can result in increased functional autonomy, ventilatory capacity and waling efficiency [109, 110, 111, 112]. Since this therapy has a major impact on social networking of COPD patients, it serves well to involve patient’s family and friends [113].
\nBody composition in COPD patients may change as the disease severity progresses. While obesity predominates in the milder stages of the disease, patients with advanced disease and emphysema tend to be underweight and have generalized muscle wasting [114, 115]. Factors other than the lung disease itself, which can lead to this shift, includes inactivity, systemic inflammation, osteoporosis and glucocorticoids use. Studies have shown an increase in mortality in COPD patients who are underweight, independent of their disease severity [116, 117]. These patients with decreased fat free mass have higher limitation to exercise tolerance and thereby reported a decreased HRQoL status in comparison to COPD patients with normal weight [118, 119, 120, 121]. Various studies have shown a survival benefit with weight gain as low as 2 kg or by increase in one body mass index unit [116, 117]. This is why nutritional education are particularly essential in rehabilitation of COPD patients.
\nEvery pulmonary rehabilitation program should include nutritional screening with measurement of BMI at the least. A more comprehensive program may also include fat free mass estimate using skinfold anthropometry or bioimpedance analysis. Estimation of osteoporosis can be done using dual energy X-ray absorptiometry (DEXA) scanning. Improvement of nutritional status requires a multi-pronged approach with utilization of both physiologic and pharmacological interventions. Endurance and strength training as described previously in this chapter can improve muscle mass as well as bone strength. Nutritional interventions include adding nutritional supplementation to patient’s diet with emphasis on adequate protein intake to maintain or restore lean body mass. Patients who are unable to eat large meals due to dyspnea can switch to frequent small meals. It has been shown that a 6-month intervention involving dietary counseling, nutritional supplementation and positive reinforcement led to a significant weight gain in advanced COPD patients [60].
\nMany COPD patients who are referred to pulmonary rehabilitation suffer from depression and anxiety [45, 122]. Recent studies have estimated prevalence of depressed mood in about 45% and anxiety in 32% of patients with moderate to advanced COPD [123, 124, 125]. Dyspnea on exertion leads to fear and anxiety anytime a COPD patient has to exercise. This severely limits their social interaction and eventually leads to depression. COPD patients can suffer from hopelessness, sense of isolation and lack of motivation. It is essential to assess the presence of depressed mood during initial evaluation in a pulmonary rehabilitation program. Family and caregiver involvement is advisable to assess the social support system for the patient.
\nIdentifying the mood disorders and deficit in the social support is an integral part of the program [114]. Patients in need can be provided with psychological and social support, which works to elevate mood, positive thinking and adaptive behavior towards disease and its management. This also improves the compliance with the pulmonary rehabilitation program. Psychological support can be provided by the physical therapist but often require a psychologist or a psychiatrist involvement.
\nVarious models of PR have been adopted worldwide. An outpatient or hospital based-outpatient setting is the most widely used model to deliver PR to COPD patient in the developed countries [126]. Current body of evidence regarding effectiveness of PR in COPD patients is based on this model. In recent years an alternative model where the site of delivery of PR is at home has been studied. Home based PR setting provides the benefit of exercise training in a familiar setting to a larger patient population. Specifically for patients with severe COPD dependent on long term oxygen therapy, this model of PR has been shown to be both safe and effective [127, 128]. While home based PR model offers convenience, it lacks the group dynamics which an outpatient model can offer. Group therapy leads to socialization, mood elevation and positive reinforcement. Additionally a home based program does not have a multidisciplinary and comprehensive structure of a hospital based outpatient setting. At the present time, choice of location of PR is dependent on patient preference, disease severity and regional availability of resources.
\nSeveral COPD patients with advanced lung disease who are bed bound or wheelchair bound are unable to participate in a conventional pulmonary rehabilitation program. To help these patients, a new modality of transcutaneous neuromuscular electrical stimulation (NMES) has been devised recently [129, 130, 131]. This technology involves application of low amplitude electric current via electrodes transcutaneously to the targeted muscle groups by depolarizing motor neurons. Low intensity electric current (10–100 mA) is delivered at stimulation frequencies between 8 and 120 Hz for duration of 250–400 ms. Although no large RCTs are available, a recent meta-analysis did report improvement in quadriceps strength and exercise capacity with NMES. Unfortunately, no significant improvement in HRQoL in moderate to severe COPD was seen [132]. Apart from debilitated COPD patients, this technology has been recommended for use during COPD exacerbation, as it has low impact on ventilation, heart rate and dyspnea [133, 134].
\nA pulmonary rehabilitation programs for COPD patients usually includes respiratory muscle training. The goal of this training is to improve the abnormal breathing pattern, which may result due to increased work of breathing, chest wall changes and poor breathing habits in COPD patients [135, 136, 137, 138]. The most commonly applied approach is through the endurance and strength training. [26]. Exercise training can lead to increase in minute ventilation, which leads to an increase in work of breathing. Constant controlled aerobic exercises of upper and lower extremities can lead to a recurrent stimulation to respiratory muscles. This helps the COPD patients to modify their breathing patterns on a day-to-day basis as well as be better prepared for an exacerbation.
\nApart from exercise training, specific breathing exercises such as diaphragmatic breathing, paced breathing with exercises and pursed lip breathing has been proven to be beneficial in COPD patients. Diaphragm, which is the main inspiratory muscle, is flattened and ineffective in patients with hyperinflated lungs. This puts these patients at a mechanical disadvantage to adequately maintain and increase their minute ventilation. COPD patients who undergo the training to improve the coordination of their diaphragmatic muscle tend to fare better overall [139].
\nMany patients with emphysema self-discover the method of purse lip breathing for faster recovery from shortness of breath post exercise. Other patients can be instructed regarding this method. It helps patients to increase alveolar ventilation, tidal volume and CO2 removal. It also leads to slow expiratory flow and decreased respiratory rate [140]. Using the same principle, respiratory muscles can be trained by using resistive breathing devices. This can be particularly useful in patients who continue to have dyspnea despite optimal medical management.
\nAdditionally COPD patients specifically with chronic bronchitis occasionally have ineffectual cough leading to difficulty in respiratory secretion clearance. Instructions on special coughing techniques (huffing, autogenic drainage) combined with oscillating expiratory breathing devices (Acapella, In-exsufflator) can prove effective [141]. Patients can be instructed to perform daily chest physiotherapy to assist in respiratory secretion clearance through postural drainage techniques [142]. A meta-analysis of 32 studies focusing on respiratory muscle training showed that it leads to improvement in respiratory muscle strength, exercise capacity and perception of exertional dyspnea [143].
\nThe beneficial effects of a comprehensive pulmonary rehabilitation program are not sustained beyond 12 months [32, 42, 144, 145]. On the other hand, repeating a pulmonary rehabilitation programs has not been found to be an effective treatment option [146]. Considering this, it is challenging to maintain the changes made in physical activity and lifestyle due to a pulmonary rehabilitation. Although there is a lack of data on maintenance programs, some centers do provide these in the hope to achieve prolonged benefits gathered in a successful rehabilitation program. There are no set guidelines to establish an optimal strategy for providing maintenance pulmonary rehabilitation. Additionally other factors such as lack of transportation to the PR center, disruption of daily life routine, absence of family support, perception regarding gains from the PR program, have impact on patient’s participation in the post PR programs. A recent multicenter RCT studying the long term (3 year) maintenance program after PR in severe COPD patients, showed a sustained beneficial effect on BODE index and 6MWD at 24 months. Although, the effect vanished beyond 2 years as at end of study only 66% of COPD patients were still adherent with the maintenance program [147].
\nVarious methods adopted to provide therapy beyond a comprehensive program include weekly telephone contacts, home exercise training with or without weekly-supervised outpatient sessions and recurrent PR program [146, 148, 149, 150, 151]. A recent meta-analysis analyzing post-PR exercise program in COPD patients suggested that such a program even though effective in maintaining a good exercise capacity with the 6 months of PR, loses its benefit beyond 1 year and has no impact on HRQoL [152]. The patient population and the interventions used were variable and results of this study need to be interpreted cautiously.
\nSince the structure of the most effective maintenance program remains elusive, it is important at this time to encourage the COPD patients to continue with healthy lifestyle changes. This can be achieved by a concerted effort of the PR staff, family members, and patients’ healthcare team. Those COPD patients who continue with the exercise routine and lifestyle changes they had learnt in the PR program tend to accumulate gains in physical endurance and psychological functioning [153].
\nPulmonary rehabilitation has a major role in the management of patients with chronic lung conditions especially COPD. The need for more convenient and efficient programs using new technology would be beneficial for patients. Tele-rehabilitation to deliver rehabilitation services over telemedicine using internet or phone can provides services to patients who live in remote areas without access to transportation. Tele-rehabilitation allows video conferencing between a central control unit and a patient at home. This will also deliver health services to patients with disability who cannot travel long distances for rehabilitation programs. Both mobile phones and video conferencing have used in few studies deliver rehabilitation services. The studies have demonstrated good compliance, decrease in exacerbations and hospitalizations, improved exercise capacity and quality of life [154, 155]. Benefits of telemonitoring in COPD patients have been described in a systemic review that showed decrease in hospitalizations and emergency room visits using telephone support for telerehabilitation [156].
\nA comprehensive multimodality pulmonary rehabilitation program is becoming an essential part of the management of COPD patients. It is not only cost effective but also scientifically proven to improve patients’ symptoms and functionality. With a gradual increase in daily activity, COPD patients are able to achieve higher HRQoL compared to pharmacotherapy alone. Despite these proven benefits, widespread utilization of PR remains poor. Multiple factors, including; physician unfamiliarity of benefits of PR, patient compliance with the exercise regimen and insurance coverage contribute to this gap. With the increasing prevalence of COPD worldwide, a safe and effective option like PR needs to be actively promoted and utilized.
\nApart from standardized exercise regimens and strength training, the emphasis of an effective PR program is on behavioral modification. This result in long lasting, positive changes on the disease course. In addition, empowering the COPD patients by educating them about disease, smoking cessation and nutrition is a crucial step in the right direction. Development of home based or telerehabilitation services may assist in reducing the disparity in access to PR for many more COPD patients.
\nAuthors declare no conflicts of interest.
\n chronic obstructive pulmonary disease acute exacerbation of chronic obstructive pulmonary disease pulmonary rehabilitation health-related quality of life randomized controlled trial neuromuscular electrical stimulation activities of daily living modified Medical Research Council 6 minute walk test functional independence measure assessment of motor and process skills functional capacity evaluation dual energy X-ray absorptiometry body mass index, airflow obstruction, dyspnea and exercise capacity
Edited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateendthirdsteppublish",topicid:"7"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"417",title:"Genetic Engineering",slug:"biochemistry-genetics-and-molecular-biology-microbiology-genetic-engineering",parent:{title:"Microbiology",slug:"biochemistry-genetics-and-molecular-biology-microbiology"},numberOfBooks:4,numberOfAuthorsAndEditors:116,numberOfWosCitations:47,numberOfCrossrefCitations:53,numberOfDimensionsCitations:122,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"biochemistry-genetics-and-molecular-biology-microbiology-genetic-engineering",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"5132",title:"Modern Tools for Genetic Engineering",subtitle:null,isOpenForSubmission:!1,hash:"37201ca138b78c27e431029445ecc675",slug:"modern-tools-for-genetic-engineering",bookSignature:"Michael S.D. Kormann",coverURL:"https://cdn.intechopen.com/books/images_new/5132.jpg",editedByType:"Edited by",editors:[{id:"173868",title:"Prof.",name:"Michael",middleName:"Sebastian Daniel",surname:"Kormann",slug:"michael-kormann",fullName:"Michael Kormann"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3359",title:"Genetic Engineering",subtitle:null,isOpenForSubmission:!1,hash:"e8f1c765a3b89770adaad569cfd851d7",slug:"genetic-engineering",bookSignature:"Idah Sithole-Niang",coverURL:"https://cdn.intechopen.com/books/images_new/3359.jpg",editedByType:"Edited by",editors:[{id:"90172",title:"Prof.",name:"Idah",middleName:null,surname:"Sithole-Niang",slug:"idah-sithole-niang",fullName:"Idah Sithole-Niang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2562",title:"Mutagenesis",subtitle:null,isOpenForSubmission:!1,hash:"7574fdd072594f99c2972bccc2585c55",slug:"mutagenesis",bookSignature:"Rajnikant Mishra",coverURL:"https://cdn.intechopen.com/books/images_new/2562.jpg",editedByType:"Edited by",editors:[{id:"144908",title:"Dr.",name:"Rajnikant",middleName:null,surname:"Mishra",slug:"rajnikant-mishra",fullName:"Rajnikant Mishra"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"620",title:"Genetic Engineering",subtitle:"Basics, New Applications and Responsibilities",isOpenForSubmission:!1,hash:"a8acb6135be37ff5f1b5050934a95b62",slug:"genetic-engineering-basics-new-applications-and-responsibilities",bookSignature:"Hugo A. Barrera-Saldaña",coverURL:"https://cdn.intechopen.com/books/images_new/620.jpg",editedByType:"Edited by",editors:[{id:"78442",title:"Dr.",name:"Hugo",middleName:"Alberto",surname:"Barrera-Saldaña",slug:"hugo-barrera-saldana",fullName:"Hugo Barrera-Saldaña"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,mostCitedChapters:[{id:"25750",doi:"10.5772/32009",title:"Gateway Vectors for Plant Genetic Engineering: Overview of Plant Vectors, Application for Bimolecular Fluorescence Complementation (BiFC) and Multigene Construction",slug:"gateway-vectors-for-plant-genetic-engineering-overview-of-plant-vectors-application-for-bimolecular-",totalDownloads:11369,totalCrossrefCites:33,totalDimensionsCites:75,book:{slug:"genetic-engineering-basics-new-applications-and-responsibilities",title:"Genetic Engineering",fullTitle:"Genetic Engineering - Basics, New Applications and Responsibilities"},signatures:"Yuji Tanaka, Tetsuya Kimura, Kazumi Hikino, Shino Goto,\nMikio Nishimura, Shoji Mano and Tsuyoshi Nakagawa",authors:[{id:"89749",title:"Prof.",name:"Tsuyoshi",middleName:null,surname:"Nakagawa",slug:"tsuyoshi-nakagawa",fullName:"Tsuyoshi Nakagawa"},{id:"124398",title:"MSc.",name:"Yuji",middleName:null,surname:"Tanaka",slug:"yuji-tanaka",fullName:"Yuji Tanaka"},{id:"124404",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Kimura",slug:"tetsuya-kimura",fullName:"Tetsuya Kimura"},{id:"124405",title:"Ms.",name:"Kazumi",middleName:null,surname:"Hikino",slug:"kazumi-hikino",fullName:"Kazumi Hikino"},{id:"124406",title:"Dr.",name:"Shino",middleName:null,surname:"Goto",slug:"shino-goto",fullName:"Shino Goto"},{id:"124407",title:"Dr.",name:"Shoji",middleName:null,surname:"Mano",slug:"shoji-mano",fullName:"Shoji Mano"},{id:"124408",title:"Prof.",name:"Mikio",middleName:null,surname:"Nishimura",slug:"mikio-nishimura",fullName:"Mikio Nishimura"}]},{id:"44799",doi:"10.5772/55573",title:"Strategies for Generating Marker-Free Transgenic Plants",slug:"strategies-for-generating-marker-free-transgenic-plants",totalDownloads:4940,totalCrossrefCites:5,totalDimensionsCites:9,book:{slug:"genetic-engineering",title:"Genetic Engineering",fullTitle:"Genetic Engineering"},signatures:"Borys Chong-Pérez and Geert Angenon",authors:[{id:"160449",title:"Prof.",name:"Geert",middleName:null,surname:"Angenon",slug:"geert-angenon",fullName:"Geert Angenon"}]},{id:"38246",doi:"10.5772/50333",title:"Mutagenesis and Temperature-Sensitive Little Machines",slug:"mutagenesis-and-temperature-sensitive-little-machines",totalDownloads:1623,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"María Pertusa, Hans Moldenhauer, Sebastián Brauchi, Ramón Latorre, Rodolfo Madrid and Patricio Orio",authors:[{id:"148089",title:"Dr.",name:"Ramon",middleName:null,surname:"Latorre",slug:"ramon-latorre",fullName:"Ramon Latorre"}]}],mostDownloadedChaptersLast30Days:[{id:"38245",title:"Mutagenesis in Plant Breeding for Disease and Pest Resistance",slug:"mutagenesis-in-plant-breeding-for-disease-and-pest-resistance",totalDownloads:6537,totalCrossrefCites:2,totalDimensionsCites:5,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Petra Kozjak and Vladimir Meglič",authors:[{id:"147785",title:"PhD.",name:"Petra",middleName:null,surname:"Kozjak",slug:"petra-kozjak",fullName:"Petra Kozjak"},{id:"154219",title:"Dr.",name:"Vladimir",middleName:null,surname:"Meglič",slug:"vladimir-meglic",fullName:"Vladimir Meglič"}]},{id:"38328",title:"Chemical Modification of Oligonucleotides: A Novel Approach Towards Gene Targeting",slug:"chemical-modification-of-oligonucleotides-a-novel-approach-towards-gene-targeting",totalDownloads:1404,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Hidetaka Torigoe and Takeshi Imanishi",authors:[{id:"145456",title:"Prof.",name:"Hidetaka",middleName:null,surname:"Torigoe",slug:"hidetaka-torigoe",fullName:"Hidetaka Torigoe"},{id:"149069",title:"Dr.",name:"Takeshi",middleName:null,surname:"Imanishi",slug:"takeshi-imanishi",fullName:"Takeshi Imanishi"}]},{id:"50176",title:"Next-Generation Therapeutics: mRNA as a Novel Therapeutic Option for Single-Gene Disorders",slug:"next-generation-therapeutics-mrna-as-a-novel-therapeutic-option-for-single-gene-disorders",totalDownloads:2061,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"modern-tools-for-genetic-engineering",title:"Modern Tools for Genetic Engineering",fullTitle:"Modern Tools for Genetic Engineering"},signatures:"Tatjana Michel, Hans-Peter Wendel and Stefanie Krajewski",authors:[{id:"45899",title:"Prof.",name:"Hans Peter",middleName:null,surname:"Wendel",slug:"hans-peter-wendel",fullName:"Hans Peter Wendel"},{id:"178484",title:"Dr.",name:"Stefanie",middleName:null,surname:"Krajewski",slug:"stefanie-krajewski",fullName:"Stefanie Krajewski"},{id:"184179",title:"MSc.",name:"Tatjana",middleName:null,surname:"Michel",slug:"tatjana-michel",fullName:"Tatjana Michel"}]},{id:"38250",title:"The Mutation of Transient Receptor Potential Vanilloid 4 (TRPV4) Cation Channel in Human Diseases",slug:"the-mutation-of-transient-receptor-potential-vanilloid-4-trpv4-cation-channel-in-human-diseases",totalDownloads:1381,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Sang Sun Kang",authors:[{id:"147133",title:"Prof.",name:"Sang Sun",middleName:null,surname:"Kang",slug:"sang-sun-kang",fullName:"Sang Sun Kang"}]},{id:"38248",title:"Bacterial Systems for Testing Spontaneous and Induced Mutations",slug:"bacterial-systems-for-testing-spontaneous-and-induced-mutations",totalDownloads:3758,totalCrossrefCites:1,totalDimensionsCites:1,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Anna Sikora, Celina Janion and Elżbieta Grzesiuk",authors:[{id:"146985",title:"Dr.",name:"Anna",middleName:null,surname:"Sikora",slug:"anna-sikora",fullName:"Anna Sikora"},{id:"146988",title:"Prof.",name:"Elżbieta",middleName:null,surname:"Grzesiuk",slug:"elzbieta-grzesiuk",fullName:"Elżbieta Grzesiuk"},{id:"146989",title:"Prof.",name:"Celina",middleName:null,surname:"Janion",slug:"celina-janion",fullName:"Celina Janion"}]},{id:"50138",title:"Gene Editing in Adult Hematopoietic Stem Cells",slug:"gene-editing-in-adult-hematopoietic-stem-cells",totalDownloads:1540,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"modern-tools-for-genetic-engineering",title:"Modern Tools for Genetic Engineering",fullTitle:"Modern Tools for Genetic Engineering"},signatures:"Sergio López-Manzaneda, Sara Fañanas-Baquero, Virginia Nieto-\nRomero, Francisco-Jose Roman-Rodríguez, Maria Fernandez-Garcia,\nMaria J. Pino-Barrio, Fatima Rodriguez-Fornes, Begoña Diez-\nCabezas, Maria Garcia-Bravo, Susana Navarro, Oscar Quintana-\nBustamante and Jose C. Segovia",authors:[{id:"35353",title:"Dr.",name:"Jose",middleName:"C",surname:"Segovia",slug:"jose-segovia",fullName:"Jose Segovia"},{id:"59062",title:"Dr.",name:"Susana",middleName:null,surname:"Navarro",slug:"susana-navarro",fullName:"Susana Navarro"},{id:"158069",title:"Dr.",name:"Oscar",middleName:null,surname:"Quintana-Bustamante",slug:"oscar-quintana-bustamante",fullName:"Oscar Quintana-Bustamante"},{id:"158742",title:"Dr.",name:"Maria",middleName:null,surname:"Garcia-Bravo",slug:"maria-garcia-bravo",fullName:"Maria Garcia-Bravo"},{id:"178374",title:"Dr.",name:"Sergio",middleName:null,surname:"López-Manzaneda",slug:"sergio-lopez-manzaneda",fullName:"Sergio López-Manzaneda"},{id:"178428",title:"MSc.",name:"Virginia",middleName:null,surname:"Nieto-Romero",slug:"virginia-nieto-romero",fullName:"Virginia Nieto-Romero"},{id:"178429",title:"MSc.",name:"Sara",middleName:null,surname:"Fañanás-Baquero",slug:"sara-fananas-baquero",fullName:"Sara Fañanás-Baquero"},{id:"184199",title:"Ph.D. Student",name:"Francisco Jose",middleName:null,surname:"Roman-Rodriguez",slug:"francisco-jose-roman-rodriguez",fullName:"Francisco Jose Roman-Rodriguez"},{id:"184200",title:"MSc.",name:"Maria",middleName:null,surname:"Fernandez-Garcia",slug:"maria-fernandez-garcia",fullName:"Maria Fernandez-Garcia"},{id:"184201",title:"MSc.",name:"María José",middleName:null,surname:"Pino-Barrio",slug:"maria-jose-pino-barrio",fullName:"María José Pino-Barrio"},{id:"184202",title:"MSc.",name:"Fatima",middleName:null,surname:"Rodriguez-Fornes",slug:"fatima-rodriguez-fornes",fullName:"Fatima Rodriguez-Fornes"},{id:"184203",title:"Dr.",name:"Begoña",middleName:null,surname:"Diez-Cabezas",slug:"begona-diez-cabezas",fullName:"Begoña Diez-Cabezas"}]},{id:"50215",title:"Insulin Gene Therapy for Type 1 Diabetes Mellitus: Unique Challenges Require Innovative Solutions",slug:"insulin-gene-therapy-for-type-1-diabetes-mellitus-unique-challenges-require-innovative-solutions",totalDownloads:1774,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"modern-tools-for-genetic-engineering",title:"Modern Tools for Genetic Engineering",fullTitle:"Modern Tools for Genetic Engineering"},signatures:"Andrew M Handorf, Hans W Sollinger and Tausif Alam",authors:[{id:"26540",title:"Dr.",name:"Hans",middleName:null,surname:"Sollinger",slug:"hans-sollinger",fullName:"Hans Sollinger"},{id:"178930",title:"Dr.",name:"Andrew",middleName:null,surname:"Handorf",slug:"andrew-handorf",fullName:"Andrew Handorf"},{id:"179017",title:"Dr.",name:"Tausif",middleName:null,surname:"Alam",slug:"tausif-alam",fullName:"Tausif Alam"}]},{id:"25750",title:"Gateway Vectors for Plant Genetic Engineering: Overview of Plant Vectors, Application for Bimolecular Fluorescence Complementation (BiFC) and Multigene Construction",slug:"gateway-vectors-for-plant-genetic-engineering-overview-of-plant-vectors-application-for-bimolecular-",totalDownloads:11369,totalCrossrefCites:33,totalDimensionsCites:75,book:{slug:"genetic-engineering-basics-new-applications-and-responsibilities",title:"Genetic Engineering",fullTitle:"Genetic Engineering - Basics, New Applications and Responsibilities"},signatures:"Yuji Tanaka, Tetsuya Kimura, Kazumi Hikino, Shino Goto,\nMikio Nishimura, Shoji Mano and Tsuyoshi Nakagawa",authors:[{id:"89749",title:"Prof.",name:"Tsuyoshi",middleName:null,surname:"Nakagawa",slug:"tsuyoshi-nakagawa",fullName:"Tsuyoshi Nakagawa"},{id:"124398",title:"MSc.",name:"Yuji",middleName:null,surname:"Tanaka",slug:"yuji-tanaka",fullName:"Yuji Tanaka"},{id:"124404",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Kimura",slug:"tetsuya-kimura",fullName:"Tetsuya Kimura"},{id:"124405",title:"Ms.",name:"Kazumi",middleName:null,surname:"Hikino",slug:"kazumi-hikino",fullName:"Kazumi Hikino"},{id:"124406",title:"Dr.",name:"Shino",middleName:null,surname:"Goto",slug:"shino-goto",fullName:"Shino Goto"},{id:"124407",title:"Dr.",name:"Shoji",middleName:null,surname:"Mano",slug:"shoji-mano",fullName:"Shoji Mano"},{id:"124408",title:"Prof.",name:"Mikio",middleName:null,surname:"Nishimura",slug:"mikio-nishimura",fullName:"Mikio Nishimura"}]},{id:"38254",title:"Mitochondrial Mutagenesis in Aging and Disease",slug:"mitochondrial-mutagenesis-in-aging-and-disease",totalDownloads:1448,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Marc Vermulst, Konstantin Khrapko and Jonathan Wanagat",authors:[{id:"144640",title:"Dr.",name:"Marc",middleName:null,surname:"Vermulst",slug:"marc-vermulst",fullName:"Marc Vermulst"}]},{id:"38252",title:"Models for Detection of Genotoxicity in vivo: Present and Future",slug:"models-for-detection-of-genotoxicity-in-vivo-present-and-future",totalDownloads:2931,totalCrossrefCites:0,totalDimensionsCites:2,book:{slug:"mutagenesis",title:"Mutagenesis",fullTitle:"Mutagenesis"},signatures:"Cherie Musgrove and Manel Camps",authors:[{id:"149057",title:"Dr.",name:"Manel",middleName:null,surname:"Camps",slug:"manel-camps",fullName:"Manel Camps"},{id:"149058",title:"Ms.",name:"Cherie",middleName:null,surname:"Musgrove",slug:"cherie-musgrove",fullName:"Cherie Musgrove"}]}],onlineFirstChaptersFilter:{topicSlug:"biochemistry-genetics-and-molecular-biology-microbiology-genetic-engineering",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/161076/jong-keun-seon",hash:"",query:{},params:{id:"161076",slug:"jong-keun-seon"},fullPath:"/profiles/161076/jong-keun-seon",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()