**8. Challenges for educational management**

138 International Perspectives of Distance Learning in Higher Education

and students through the provision of services that facilitate teaching, learning and education-related administrative tasks. The most important component in the deployment of a blended learning programme is to recognise the role of the instructor and the new roles

However, integrating more sophisticated technologies requires a strategic decision, to train, support and adequately reward staff involved in such initiatives. For instructors, there is a significant adjustment required in their role. Berge (1998) and Vrasidas and Zembylas (2004) suggest that instructors are often asked to develop programmes using technology to support their deliver without the proper skill-sets or supports in place. Staff enablers as identified by this research include further up-skilling, support in the creation of web pages and support in the use of synchronous technologies such as voice over IP (VoIP) and web technologies. Greater flexibility, learning and integration of new technologies, and providing feedback in a more flexible manner are all roles that management in institutions must facilitate. In summary, if these challenges are addressed, synchronous communication technologies such as whiteboards or VoIP can play a key role in the successful deployment of

The instructor has a key role to play in the successful delivery of a blended learning programme. The instructor's engagement will be a key determinant of the success or otherwise of any blended learning initiative. For educational institutions, the challenge is in communicating effectively to the wider community the details and features of these types of programmes and ensuring the programme is effectively structured and delivered. Adams (2004) suggests that computer based learning has three elements; (i) hardware, (ii) software and (iii) 'underware' – the pedagogy that underpins the e-learning development. Tham and Werner (2005) would suggest that as educators there is a requirement for a variety of skills sets or "hats" including (i) a technological hat, (ii) a pedagogical hat and (iii) a social hat.

Tham and Werner (2005) highlight studies that indicate that instructors in an online

 A technological hat – educators must understand the application software and also the implications of technology for adopting different strategies in teaching. Using the

 A social hat – in an online environment for the instructor to establish a rapport with students the technical communication tools should be used to establish a friendly,

Senior management in institutions must harness the power of technology to deliver the curriculum to lifelong learners while recognising that the set of instructional skills required are quite different, the cohort of students are different and the role of the institution,

available technology to enhance student learning is not an easy undertaking. A pedagogical hat – with a virtual classroom the tool/applications used to monitor or raise the intellectual skills of students requires the instructor to adopt the right tools and not simply use the tools that are available. Creativity is elementary to design of a

environment must fulfil many roles or "hats". These hats include:

course that brings students closer in an online environment.

cohesive and comfortable learning environment.

instructor and student must adopt to this changing dynamic.

and responsibilities that the instructor must take on.

programmes.

**7. Online instructional skills**

It is incumbent on management in higher education to make a strategic decision on the role of technology in the delivery of learning. If the strategic decision is to embrace technology in the delivery of learning, then budgets need to be dedicated to resourcing appropriately the technological infrastructure, support and training mechanisms and appropriate rewards and recognition systems for staff involved in the delivery of programmes.

For staff new to this type of programme delivery, some training should be provided to guide instructors on how to manage a course and to create online content. Given that most institutions will start with a learning management system (LMS) as the fundamental hosting framework for the delivery of these types of programmes, sufficient training should also be provided on the deploying of the features within these systems.

In deploying these types of programmes effectively there is a "hardware" perspective, i.e. technological component, that needs to be considered, and a "software" perspective, i.e. the various instructional roles and approaches, that the instructor must assume. Based on the literature review and the analysis of the programme in Waterford Institute of Technology (WIT) in Ireland, strategically there are a number of key steps that should be considered in deploying initiatives of this type. These are outlined in table 3.

Table 3. Steps to Enable Delivery of a Blended Learning Programme

As funding mechanisms continue to change and rapid advances in information and communications technology (ICT) continue to transform the way education is delivered, developing a framework to deploy learning to address the diverse lifelong learning needs of professionals presents a challenge. Adopting ICT to support and facilitate the development of educational programmes is at various stages of the technological adoption cycle in higher education. It represents in many cases an unknown and as such carries significant risk in terms of costs if not deployed successfully. A review of the literature suggests that there is no unique formula to apply for the successful development and delivery of blended learning. For many institutions the new technologies that are available represent largely additional expenses that are difficult to quantify (Twigg, 2003). Coupled with this, the range of cost estimates that can be incurred in the development of e-learning vary, from small financial resources required to huge financial commitment (Mayer, 2003).

With the growing acceptance of e-learning technologies and the increasing need of access to remote learning opportunities, administrators of higher-level institutions face; (i)

Strategically Integrating Blended Learning to Deliver Lifelong Learning 141

To capitalise on this research and bridge the gap between, (i) higher education, (ii) the requirements of the various professional bodies and (iii) the needs of industry, there are a

1. Establish and test the infrastructure and framework which will act as the host platform

2. Establish the appropriate learning outcomes and competencies required by the

3. Determine the breakdown of traditional and online delivery of the learning. As part of this, ensure that as many methods of instruction and learning as possible, i.e. both

4. Ensure that the content delivered will be recognised by the professional bodies, industry, regulatory bodies and individual as eligible as part of CPD. For educational institutions, this means building links with the professional bodies and ensuring the quality of the delivered learning will meet both the competencies and learning

Through the execution of these various steps, an effective programme of lifelong learning, meeting both the professional institutions and industry's learning needs can be deployed. Educational institutions are in a better position than most to capitilise on this through the formal quality assurance systems that exist in the sector and in individual institutions, through undergraduate programmes developed which fulfil the criteria of the various

Developing and deploying an initiative to deliver lifelong learning addressing the continuing learning needs of professionals can be a challenging task, which can consume considerable time and resources without any guarantee that the outcome will be successful. The creation of effective online resources, also identified as important, is a complex

The term blended learning has been widely adopted to depict combinations of face-to-face and technology-based learning (Stubbs et al., 2006). No two blended learning designs are identical, which introduces the great complexity of blended learning (Garrison and Kanuka, 2004). Both previous research and the analysis that has been undertaken in this exploration, indicate that in the development of a framework for deploying blended lifelong learning is a complex undertaking. However, it may be useful to construct a framework that will assist in deploying lifelong learning. This framework, outlined in figure 2, is constructed around four

Blended learning offers institutions the opportunity to engage in using technology in

series of steps that should be undertaken. These are:

professional bodies

for the technology-facilitated lifelong learning initiative

formal and informal methods of learning, are incorporated

challenge that educational institutions and educators continue to face.

outcomes required by multitude of stakeholders

professional bodies to meet industry needs.

**9. Framework for blended learning**

key parameters: 1. Participants

3. Online learning

4. Traditional Instruction.

2. The delivery of the instruction

conjunction with traditional delivery to offer learning.

technological, (ii) organisational, (iii) pedagogical and (iv) cultural challenges in helping to integrate these changes (Howell et al., 2004). This research supports the work of Forsyth (2003), which suggests that students and tutors have different support needs as outlined in figure 1.

Source: Forsyth (2003)

Fig. 1. Summary of Tutor and Student Support Needs

The design, development and implementation of e-learning in the delivery of learning can represent a significant investment without any guarantee of success. Therefore it is vital that a strategic approach is embraced in deploying any initiative using technology. Embracing a strategic approach can result in the successful deployment of a blended programme meeting the needs of professionals.

As demonstrated earlier in the literature and succinctly captured by Sadler-Smith et al. (2000), individuals who involve themselves in continuing professional development (CPD) are likely to have clear preferences for different learning methods and activities. These are key considerations in developing e-learning programmes addressing the CPD needs of learners.

The integration and interaction of (i) technology, (ii) traditional instruction, (iii) the instructor and (iv) the participant are key components in any blended learning programme. Based on a review of the literature and previous initiatives, "flexibility" captures the most significant change that must be embraced for a blended learning CPD approach to be successful. Educational institutions, individual instructors and participants must become flexible in the successful collaboration and delivery of a blended programme.

As identified by Thomas (1995) and Browell (2000), the benefits to higher education in becoming involved in providing lifelong learning include; (i) offering the potential for closer links with industry and the professions, (ii) opportunity for funding to carry out research and consultancy and (iii) information feeds back into undergraduate programmes to ensure relevance to industry requirements.

technological, (ii) organisational, (iii) pedagogical and (iv) cultural challenges in helping to integrate these changes (Howell et al., 2004). This research supports the work of Forsyth (2003), which suggests that students and tutors have different support needs as outlined in

The design, development and implementation of e-learning in the delivery of learning can represent a significant investment without any guarantee of success. Therefore it is vital that a strategic approach is embraced in deploying any initiative using technology. Embracing a strategic approach can result in the successful deployment of a blended programme

As demonstrated earlier in the literature and succinctly captured by Sadler-Smith et al. (2000), individuals who involve themselves in continuing professional development (CPD) are likely to have clear preferences for different learning methods and activities. These are key considerations in developing e-learning programmes addressing the CPD needs of learners. The integration and interaction of (i) technology, (ii) traditional instruction, (iii) the instructor and (iv) the participant are key components in any blended learning programme. Based on a review of the literature and previous initiatives, "flexibility" captures the most significant change that must be embraced for a blended learning CPD approach to be successful. Educational institutions, individual instructors and participants must become

As identified by Thomas (1995) and Browell (2000), the benefits to higher education in becoming involved in providing lifelong learning include; (i) offering the potential for closer links with industry and the professions, (ii) opportunity for funding to carry out research and consultancy and (iii) information feeds back into undergraduate programmes to ensure

flexible in the successful collaboration and delivery of a blended programme.

figure 1.

Source: Forsyth (2003)

meeting the needs of professionals.

relevance to industry requirements.

Fig. 1. Summary of Tutor and Student Support Needs

To capitalise on this research and bridge the gap between, (i) higher education, (ii) the requirements of the various professional bodies and (iii) the needs of industry, there are a series of steps that should be undertaken. These are:

Through the execution of these various steps, an effective programme of lifelong learning, meeting both the professional institutions and industry's learning needs can be deployed. Educational institutions are in a better position than most to capitilise on this through the formal quality assurance systems that exist in the sector and in individual institutions, through undergraduate programmes developed which fulfil the criteria of the various professional bodies to meet industry needs.


*5.2. Case Study*

In this section, to demonstrate the applicability and capability of the proposed model, a case study in a plaster-producing company is presented. In a traditional statistical process control system, after gathering the data, the following steps are done:

The proposed ISPC model, designed in Matlab, can adequately perform the above operations (Figure 13). Here, pursuant to the plaster-producing experts' opinion, if "Cpk > 1", the chart is considered as the baseline for interpreting the process. As can be seen in the ISPC implementation flow chart, after collecting the process data, the baseline chart should be set by eliminating and replacing points beyond the control limits of new data. As shown in Figure 14, the normality test was done, where the normality assumption was valid, and "Cpk > 1" in control mode. After drawing the baseline chart, the actual data of the process were inserted and checked and analyzed by the desired control charts. As illustrated in Figure 15, although there is no "out of control" mode within the "R-chart", the process was unable to meet specifications due to "Cpk < 1", being equal to 0.81 (Figure 16). On the other hand, by choosing the "X-bar chart" (Figure 17), the user receives the following error message: "X-bar chart is out of control" (Figure 18). Then, the ES using "Western Electric tests" announces that "out of control" modes may have the following reasons: "carelessness in the measurement, machinery stop, or off-spec materials". Later, the user receives a suggestion message from ES to check the unnatural patterns identified by NN (Figure 19). As can be seen in Figure 20, not only was the "downward shift pattern" in the "X-bar chart" identified by the NN, but the "starting point" of the unnatural pattern was estimated (point 6). The "shift magnitude parameter" (−0.161) was also determined. In this scenario, because of the appearance of a "downward shift pattern" and based on user observation, which was "kiln body scarlet", the reason for the deviation was recognized as the "temperature exchange of kiln with the environment due to the loss of refractory and thickness". "Establishment of maintenance and inspection of refractory" was also recommended as corrective or preventive activities. In this scenario, by making corrective actions and following re-sampling the process (Figure 21), "out of control" modes did not appear in the control charts anymore (Figure 22) and, furthermore, "process capability" increased from Cpk = 0.81 to Cpk = 1.15 (Figure 23). The experimental results show that corrective actions could significantly contribute to process recovery. Thus, the proposed fault diagnosis system could be used to support decision-makers of the plaster production.

**Figure 13.** ISPC implementation flow chart.

**Figure 14.** Normality test and process capability calculation.

**Figure 15.** X-bar chart in "out of control" mode.

**Figure 16.** Process capability calculation.

**Figure 17.** Request for analyzing the X-bar chart.

**Figure 18.** X-bar chart reasoning by Western Electric tests.

**Figure 19.** Pattern recognition in X-bar chart by NN.

**Figure 20.** Determining Cpk, unnatural pattern, parameters, and recovery actions.

**Figure 21.** Inserting new dataset.

**Figure 22.** X-bar and R charts in control mode.

**Figure 23.** Capability of the process after performing corrective actions.


**Author details**

Cameron T. McDaniel, Warunya Panmanee and Daniel J. Hassett\*

\*Address all correspondence to<EMAIL_ADDRESS>
University of Cincinnati, College of Medicine, Cincinnati, OH. Department of Molecular Ge‐ netics, Biochemistry, and Microbiology, USA


**2.4. Oxidation rates at higher temperatures and Zircaloy-4**

Although the TREAT design basis accident shows that the cladding temperature does not exceed 820°C, higher temperature data are also of interest. The above three correlations were extrapolated to 900°C and are shown in **Figure 6** along with other data.

**Figure 6.** Comparison of correlations and data in the high temperature range.

Hayes [19] made measurements on zirconium in moist air up to and including 900°C. Hayes was only able to obtain oxidation data at 900°C for 1 hour whereas his 500 to 800°C data were gathered over a 24 hour period. As shown in **Figure 6**, except for the 800°C data point, the oxidation rate was higher for zirconium oxidation in moist air than the Zircaloy-2 rates of Kendall. Other 900°C data include measurements at Argonne reported by Natesan [4] on bare Zircaloy-4 up to 900°C, which is also shown in **Figure 6**. Again, this is higher than the Zircaloy-2 data.

Hayes [19] concluded that the increase in the oxidation rate at 900°C is due to the change from alpha phase zirconium to beta phase zirconium at 862°C. He states "Microscopic examination of all specimens shows that there is no evidence of oxygen or nitrogen penetration into the body of the metal below 700°C. Short time exposures of less than 1 hour at 800°C produced only oxide surface layers and showed no evidences of further penetration. The specimens exposed for 1 hour and longer showed the intragranular rods and coarsened grain boundaries found in the oxygen series. In the 900°C series, it was found that the diffusion was extremely rapid. In one test with a thicker section, oxides were observed at the center of a quarter-inch (6.3 mm) sheet, which had been held at this temperature only 30 min. It appears probable that this sudden vulnerability to oxygen penetration can be ascribed to the change in volume that takes place at 862°C when the close-packed, hexagonal, alpha phase transforms to the bodycentered, cubic beta form."

This large increase in the rate is not seen for Zircaloy-4, but perhaps this one metal sample was not representative. The design basis reactivity insertion accident maximum temperature is 820°C and this is below the zirconium phase change of 862°C. Although zirconium data in moist air and the Zircaloy-4 data are higher than the 1955 Kendall Zircaloy-2 correlation, the experience with the TREAT cladding is that the Kendall correlation in the dry climate of the INL and the less reactive Zircaloy-3 cladding has conservatively bounded the oxide growth. If there has been any oxide growth so far on the fuel, it is less than the uncertainty in the measurements of 0.5 mils [20]. Based on the continued low oxide buildup reported in Mouring [21] and Kramer [20], the conservative method of estimating oxide buildup is sufficient with visual observation if the computed buildup is greater than 3 mils or if the temperature of a transient exceeds 600°C.

#### **2.5. Corrosion rate summary**

correlation which is used by TREAT to estimate the amount of oxide which has formed on the fuel does so conservatively. Note no transients performed so far have brought the fuel or

**Figure 5.** Comparison of the Kendall and Sandia correlations and Argonne Zircaloy-3 values.

extrapolated to 900°C and are shown in **Figure 6** along with other data.

Although the TREAT design basis accident shows that the cladding temperature does not exceed 820°C, higher temperature data are also of interest. The above three correlations were

Hayes [19] made measurements on zirconium in moist air up to and including 900°C. Hayes was only able to obtain oxidation data at 900°C for 1 hour whereas his 500 to 800°C data were gathered over a 24 hour period. As shown in **Figure 6**, except for the 800°C data point, the oxidation rate was higher for zirconium oxidation in moist air than the Zircaloy-2 rates of

**2.4. Oxidation rates at higher temperatures and Zircaloy-4**

**Figure 6.** Comparison of correlations and data in the high temperature range.

cladding above 600°C.

68 Nuclear Material Performance

In summary, to conservatively calculate oxide buildup on Zircaloy-3, use the oxide buildup rate equation for Zircaloy-2 which is

$$M\_{\text{gain}} = 8.5 \times 10^6 \text{ \* } t \text{ \* } e^{\left(\frac{-3.1 \times 10^4}{1.9872 \text{ \*} (T + 273)}\right)}\tag{15}$$

Where *M*gain is in mg/cm2 and *T* is temperature in °C and *t* in hours.

The relations between the weight gain due to oxide buildup, *M*gain, the metal loss thickness, and the oxide thickness,*TZrO*2 , are:

$$T\_{\rm z} = 0.172 \, ^\ast \overline{M}\_{\rm gain} \, T\_{\rm zO\_2} = 0.253 \, ^\ast \overline{M}\_{\rm gain} \, T\_{\rm z} = 0.680 \, ^\ast T\_{\rm zO\_2} \tag{16}$$

Zirc Lost 0.680 Oxide Thickness =


**4.1 Metabolites**

The majority of studies concerning the trapezius in chronic trapezius myalgia have reported increases in the interstitial concentrations of lactate and pyruvate (Flodgren et al., 2010; Flodgren et al., 2006; Larsson et al., 2008; Rosendal et al., 2004b; Sjogaard et al., 2010). However, Flodgren et al. (Flodgren et al., 2010; Flodgren et al., 2006) did not compensate for RR and their results might be biased.

There are several possible explanations for the generally higher interstitial levels of pyruvate levels in chronic trapezius myalgia and in the trapezius of patients with FMS. For example, changes in the lactate-pyruvate metabolism via lactate dehydrogenase isoforms may result in higher pyruvate levels (Philip et al., 2005). Another explanation is a reduction in tissue oxygenation in FMS (Bengtsson, 2002) and chronic trapezius myalgia (Larsson et al., 2004), reductions that may result in higher pyruvate and higher lactate concentrations due to a shift towards an anaerobic state. A lower fitness level is a third explanation as a low fitness level means more frequent reliance on anaerobic metabolism. However, it is unknown if a general deconditioning in these two pain conditions involves the postural trapezius. The aerobic capacity of a muscle is largely governed by the number of mitochondria and their enzymes (Weibel & Hoppeler, 2005). The mitochondrial density increases as result of exercise and this increased density affects the level of metabolites (i.e., enhanced aerobic capacity) (Norrbom, 2008). Lower capillary density and/or enzymes associated with aerobic metabolism have been reported in FMS and in chronic trapezius myalgia (Larsson et al., 2004; Lindh et al., 1995). For FMS and chronic trapezius myalgia, the trapezius muscle fibres can appear with alterations in mitochondrial content and distribution, e.g., moth-eaten fibres and ragged red-fibres (Bengtsson, 2002; Bengtsson et al., 1986; Larsson et al., 2000; Larsson et al., 2004).

The role of lactate is complex. Lactate may assist in the detection of exercise stress before tissue damage occurs and can be exchanged rapidly among tissue compartments where it may be oxidized as a fuel or reconverted to form pyruvate or glucose (Gladden, 2004; Kim et al., 2007; Philip et al., 2005; Robergs et al., 2004). Lactate is also involved in peripheral nociception and it appears to facilitate the response of the acid-sensing ion channel 3 (ASIC-3) to low pH (Kim et al., 2007). Such ASIC channels are considered to be molecular transducers for nociception and mechanosensation (Kim et al., 2007).

To summarize, most studies of myalgic trapezius muscles show significant increases in interstitial levels of lactate and pyruvate. These results might be explained by decreased fitness level, reduced tissue oxygenation, increased muscle activation, and/or damaged mitochondria.

#### **4.2 Pain-related substances**

### **4.2.1 Glutamate**

Two of the studies of chronic trapezius myalgia (Larsson et al., 2008; Rosendal et al., 2004b), which are markedly larger than the third study (Flodgren et al., 2005), found significant increases in the interstitial concentrations of glutamate. A possible difference between subjects of these studies may contribute to the inconsistent glutamate finding. The myalgic

Potential Muscle Biomarkers of Chronic Myalgia in Humans –

**4.2.3 Bradykinin (BKN) and Kallidin (KAL)**

KAL for nociception and pain in patients with chronic pain.

Increased interstitial potassium levels may be related to muscle pain (Graven-Nielsen et al., 1997). Green et al., however, did not find potassium related to acute ischaemic myalgia in

**4.2.4 Potassium**

A Systematic Review of Microdialysis Studies 121

indicate significantly increased levels of 5-HT in the whole spectrum of severity of chronic trapezius myalgia and these findings agree with other studies of muscle pain conditions such as myalgic masseter muscle (Ernberg et al., 1999) (**Table 4**) and chronic whiplash associated pain including trapezius pain (Gerdle et al., 2008c) (**Table 2**). The finding that there are higher interstitial levels of 5-HT in chronic trapezius myalgia than in controls at rest agrees with other studies that also found that 5-HT is a peripheral pro-nociceptive substance activated by afferents and by the release of other substances (Saria et al., 1990; Sommer, 2004). The results of the present systematic review clearly indicate that 5-HT can

BKN and KAL are kinins – a group of structurally related 9-11 amino acid peptides that are produced by kallikrein-mediated enzymatic cleavage of kininogen (Coutaux et al., 2005; Riedel & Neeck, 2001; Wang et al., 2006). Kinins mediate their effects via two different G protein coupled receptors, B1 and B2, that provoke an increase in intracellular Ca2+ (Meyer et al., 2006; Zubakova et al., 2008). In normal tissue in the acute situation, BKN and KAL act via the B2 receptor. In the chronic phase of the response of tissue injury and infection, B1 receptors are expressed by BKN and KAL via this receptor (Calixto et al., 2004; Coutaux et al., 2005; Couture et al., 2001; Graven-Nielsen & Mense, 2001; McMahon et al., 2006). Interstitial muscle BKN and KAL have been suggested as algesic kinins involved in muscle pain. BKN was the first inflammatory mediator recognized to have potent hyperalgesic properties (Levine & Reichling, 1999). BKN induces pain and modifies the receptive fields of dorsal horn neurons to noxious stimuli in humans when administered in different ways (Boix et al., 2005; Meyer et al., 2006). BKN and cytokines are central factors in the link between tissue damage and inflammatory responses (Coutaux et al., 2005). Moreover, BKN is a potent vasodilatator and is increased in the interstitium of muscle during exercise (Clifford & Hellsten, 2004; Schmelz et al., 2003; Stewart & Rittweger, 2006). Animal studies have shown that BKN can both excite (i.e., algogenic) and sensitize nociceptors (Levine & Reichling, 1999; Wang et al., 2006). The present review identified four studies investigating the interstitial concentrations of BKN and/or Kallidin (Gerdle et al., 2008b; Larsson et al., 2008; Shah et al., 2008; Shah et al., 2005). The relatively small studies conducted by Shah et al. (Shah et al., 2008; Shah et al., 2005) clearly indicated that BKN was involved since increased levels of BKN in subjects with active trigger points and the levels were higher in the trapezius (with pain) than in a pain-free distant muscle. In contrast no significant differences in BKN were found between patients and controls in a field study and a laboratory study, (Gerdle et al., 2008b; Larsson et al., 2008) The difference in results between the above mentioned studies could be due to the fact that alterations in BKN might be very localized (i.e., in the trigger points) and not generally found in the aching trapezius muscle. KAL was only investigated in one study and increased in chronic trapezius myalgia but not in the trapezius of chronic WAD compared to controls (Gerdle et al., 2008b). Clearly, more pathophysiological *in vivo* studies are necessary in order to understand the roles of BKN and

be a potential biomarker of different types and severity of chronic myalgia.

subjects studied by Larsson et al. and Rosendal et al. (Larsson et al., 2008; Rosendal et al., 2004b) comprised subjects reporting considerable pain and had distinct current muscular signs confirmed at clinical examination. The pain history, the present pain, and clinical muscular neck status of the subjects are very sparsely presented in the Flodgren study (Flodgren et al., 2005). Moreover, one study found the painful masseter was significantly associated with increased glutamate (Castrillon et al., 2010).

Glutamate, a pain modulator in the human central nervous system, acts via the N-methyl-Daspartate (NMDA) receptor (Coggeshall & Carlton, 1997) (Hudspith, 1997) and influences peripheral pain processing (Carlton, 2001; Varney & Gereau, 2002 ), e.g., muscle inflammation and delayed onset muscle soreness (Cairns et al., 2001a; Cairns et al., 2001b; Cairns et al., 2003; Svensson et al., 2003; Svensson et al., 2005; Tegeder et al., 2002 ). Glutamate is released from peripheral afferent nerve terminals (Miller et al., 2011). Studies of animals have shown that glutamate receptors are located on the peripheral ends of smalldiameter primary afferents in several tissues such as muscle (Coggeshall & Carlton, 1998). Inflammatory animal models reveal increased levels of glutamate in peripheral tissues and nociceptive behaviours (Miller et al., 2011). Several studies have demonstrated that injections of glutamate increase pain intensity (Cairns et al., 2003; Gazerani et al., 2006). A review from 2008 concluded that elevation of interstitial glutamate in skeletal muscle alters pain sensitivity in healthy humans and is associated with pain symptoms in some chronic non-inflammatory muscle pain conditions (Cairns & Dong, 2008), which are probably mediated through activation of peripheral excitatory amino acid receptors located on the terminal ends of nociceptors. The present review mainly supports the conclusions of that review. However, the interstitial concentrations of glutamate were not increased in the trapezius of patients with chronic WAD (Gerdle et al., 2008c) or in patients with fibromyalgia (Gerdle et al., 2010). One difference between chronic trapezius myalgia and the two other conditions might be the more widespread (spatial) hyperalgesia in the two latter conditions (Arendt-Nielsen & Graven-Nielsen, 2003; Wallin et al., 2011).

#### **4.2.2 Serotonin**

Serotonin (5-hydroxtryptamine, 5-HT) is involved in the central and peripheral modulation of nociceptive pain and hyperalgesia (Sommer, 2004). 5-HT is synthesized in brain neurons from the essential amino acid tryptophan and released from platelets and mast cells in the periphery due to tissue damage (Mense, 1993). Whether 5-HT has an analgesic or hyperalgesic action depends on the cell type and type of receptor it targets. Currently, seven receptor families have been identified. These receptors are cell-surface proteins that bind 5- HT and trigger intracellular changes that influence the behaviour of cells and explain the broad physiological actions and distribution of this biochemical mediator. According to animal studies, the 5-HT receptor classes currently identified, the 5-HT1 and the 5-HT2, may be involved in mainly chemical and thermal hyperalgesia (Ernberg, 2008). 5-HT activates the descending endogenous pain system and this inhibits centrally mediated pain transduction (Sommer, 2006; Suzuki et al., 2004). In the periphery, 5-HT sensitizes afferent nerve fibres, contributing to hyperalgesia in inflammation and nerve injury (Giordano & Rogers, 1989; Sommer, 2004; Taiwo & Levine, 1992). Intramuscular administration of 5-HT into the human masseter muscle has been demonstrated to induce pain (Ernberg et al., 2006). The studies identified in this systematic review concerning chronic trapezius myalgia (**Table 1**) clearly

subjects studied by Larsson et al. and Rosendal et al. (Larsson et al., 2008; Rosendal et al., 2004b) comprised subjects reporting considerable pain and had distinct current muscular signs confirmed at clinical examination. The pain history, the present pain, and clinical muscular neck status of the subjects are very sparsely presented in the Flodgren study (Flodgren et al., 2005). Moreover, one study found the painful masseter was significantly

Glutamate, a pain modulator in the human central nervous system, acts via the N-methyl-Daspartate (NMDA) receptor (Coggeshall & Carlton, 1997) (Hudspith, 1997) and influences peripheral pain processing (Carlton, 2001; Varney & Gereau, 2002 ), e.g., muscle inflammation and delayed onset muscle soreness (Cairns et al., 2001a; Cairns et al., 2001b; Cairns et al., 2003; Svensson et al., 2003; Svensson et al., 2005; Tegeder et al., 2002 ). Glutamate is released from peripheral afferent nerve terminals (Miller et al., 2011). Studies of animals have shown that glutamate receptors are located on the peripheral ends of smalldiameter primary afferents in several tissues such as muscle (Coggeshall & Carlton, 1998). Inflammatory animal models reveal increased levels of glutamate in peripheral tissues and nociceptive behaviours (Miller et al., 2011). Several studies have demonstrated that injections of glutamate increase pain intensity (Cairns et al., 2003; Gazerani et al., 2006). A review from 2008 concluded that elevation of interstitial glutamate in skeletal muscle alters pain sensitivity in healthy humans and is associated with pain symptoms in some chronic non-inflammatory muscle pain conditions (Cairns & Dong, 2008), which are probably mediated through activation of peripheral excitatory amino acid receptors located on the terminal ends of nociceptors. The present review mainly supports the conclusions of that review. However, the interstitial concentrations of glutamate were not increased in the trapezius of patients with chronic WAD (Gerdle et al., 2008c) or in patients with fibromyalgia (Gerdle et al., 2010). One difference between chronic trapezius myalgia and the two other conditions might be the more widespread (spatial) hyperalgesia in the two latter

associated with increased glutamate (Castrillon et al., 2010).

conditions (Arendt-Nielsen & Graven-Nielsen, 2003; Wallin et al., 2011).

Serotonin (5-hydroxtryptamine, 5-HT) is involved in the central and peripheral modulation of nociceptive pain and hyperalgesia (Sommer, 2004). 5-HT is synthesized in brain neurons from the essential amino acid tryptophan and released from platelets and mast cells in the periphery due to tissue damage (Mense, 1993). Whether 5-HT has an analgesic or hyperalgesic action depends on the cell type and type of receptor it targets. Currently, seven receptor families have been identified. These receptors are cell-surface proteins that bind 5- HT and trigger intracellular changes that influence the behaviour of cells and explain the broad physiological actions and distribution of this biochemical mediator. According to animal studies, the 5-HT receptor classes currently identified, the 5-HT1 and the 5-HT2, may be involved in mainly chemical and thermal hyperalgesia (Ernberg, 2008). 5-HT activates the descending endogenous pain system and this inhibits centrally mediated pain transduction (Sommer, 2006; Suzuki et al., 2004). In the periphery, 5-HT sensitizes afferent nerve fibres, contributing to hyperalgesia in inflammation and nerve injury (Giordano & Rogers, 1989; Sommer, 2004; Taiwo & Levine, 1992). Intramuscular administration of 5-HT into the human masseter muscle has been demonstrated to induce pain (Ernberg et al., 2006). The studies identified in this systematic review concerning chronic trapezius myalgia (**Table 1**) clearly

**4.2.2 Serotonin**

indicate significantly increased levels of 5-HT in the whole spectrum of severity of chronic trapezius myalgia and these findings agree with other studies of muscle pain conditions such as myalgic masseter muscle (Ernberg et al., 1999) (**Table 4**) and chronic whiplash associated pain including trapezius pain (Gerdle et al., 2008c) (**Table 2**). The finding that there are higher interstitial levels of 5-HT in chronic trapezius myalgia than in controls at rest agrees with other studies that also found that 5-HT is a peripheral pro-nociceptive substance activated by afferents and by the release of other substances (Saria et al., 1990; Sommer, 2004). The results of the present systematic review clearly indicate that 5-HT can be a potential biomarker of different types and severity of chronic myalgia.


**Abstract**

Palliative care aims at improving the quality of life of a patient who is suffering from a chronic serious ailment like that of advanced cancer. Nobody wants to be away from his/her own family, especially when it's known, he has limited days to live in this world. A patient gets the best treatment when it's given in his own home and that too by his close ones. When palliative care is provided at the patient's home, it provides a sense of safety, privacy, confidentiality and peace of mind for the patient. Specialist home-based palliative care improves symptom control, health-related communication and psychosocial support. It helps in better preparing the patient and the family members to accept death. It is provided by a team of trained members which includes doctor, nurse, social worker, volunteers, physiotherapist etc. They pay regular visits at the home of the patient and provide necessary health care to the patient. Considering the increasing cost of treatment of chronic illnesses, it's sometimes hard on the part of the family to continue treatment in a hospital or hospice. It's especially true in scenarios where population are not protected financially, in countries like India. The family members also play a vital role in home-based palliative care. They get trained from the team to learn the basics of palliation. Home based palliative care needs to be integrated into regular home health care services.

**Keywords:** palliative care, home based, quality of life, Home PAL


**3. Evaluation of "the" hypothesis**

#### **3.1. The support of a systemic theory of dental caries and K2 as a critical component**

The "old" theory of dental health, called the 'acid theory,' has been linked to the oral environment as an isolated and unique process, involving the bacteria-acid axis, as it is the only cause-effect relationship.

The systemic version or theory of dental caries acknowledges the effect of refined carbohydrates on oral cavity through the impact of the hypothalamus and the endocrine system. Earlier, free radicals like ROS, typically having been construed as "exhaust energy" from mitochondria. *However, they are now thought of as "critical signals," conveyed to the hypothalamus in order to influence the secretion of hormones, like parotid hormone and insulin. The major task to be undertaken now is: find which nutrients optimally affect the hypothalamus and which would maintain the centrifugal fluid flow through the teeth*. Antioxidants such as EGCG of green tea have proven effective. Vitamin K2, however, may serve as a more potent nutrient.

#### **3.2. What we hope to learn from Dr. Price's discovery**

The exocrine functions of the salivary glands, i.e., the composition of the saliva, are nutritionally related. As for the prevention of dental caries, optimum nutrition with fat soluble vitamins like K2 may serve as much more significant factor, than the role of traditional dental recommendations which goes like this: *Eat less sugar to minimize the production of bacterial acids*  *in the oral cavity*. Dental disease will be construed and recognized as an inflammation related degenerative lifestyle disease in line with cardiovascular incidents, as well as with bone brittleness (osteoporosis) and diabetes mellitus.