Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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This achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
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We are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
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Thank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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\r\n\tNext-generation textiles represent an exciting and interesting topic within the textiles sector. They are an intersection set between life science (for example medicine, microbiology, and comfort or strain) and technical applications (textile chemistry, engineering, and testing and certification). Developments in one of these areas affect the other one; for example, the invention of superabsorbent and gel-forming materials affected the production of a new type of baby diapers. Next-generation textiles can also be considered an important part of technical textiles, being used for different purposes such as chemical and biohazard protection. They present an important aspect from an economic point of view and the necessity for their production has been increasing; for example, a huge necessity for smart medical textiles comes from the increase of the elderly population in developed countries. In the last few decades, the rapid development of command cotton fabrics also occurred. This affects all textile sectors, for example, biodegradable fibers for implantations, three-dimension spacer fabrics, and reduction of bacterial growth by using silver ion-based textiles finishing. In this and other ways, the fields concerning the next-generation textiles have been growing rapidly and are becoming a more complex area to understand.
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1. Introduction
\n
The story of vitamin K goes back to the 1930s, when Henrik Dam at the University of Copenhagen isolated an antihemorrhagic vitamin that was fat soluble but different from previously isolated vitamins A, D, and E [1]. He found high concentrations of the vitamin in hog liver fat and hemp seed, but found it to be virtually absent in cod liver oil while testing a variety of animal organs, hen eggs, cereals, seeds, vegetables, and various fats and oils including butter fat. The initial quantification was all based on the time required to coagulate blood from a chicken. The term “vitamin K” was used as short for the German term “koagulation.” Because of the type of assay used, all vitamin K factors, whether K1 or K2, were thought to be useful only for coagulation of the blood.
\n
At the same time as Henrik Dam was working out the details of the antihemorrhagic vitamin, there was another investigator working in the USA with a vitamin factor not found in cod liver oil, but which worked synergistically with them to promote proper mineralization, bone growth, and to prevent dental caries [2]. Dr. Weston Price found that the amount of the factor in mammalian milk varied with the “nutrition of the animal,” with highest levels from milk of cows that were consuming rapidly growing green grass. Because Dr. Price’s assay was based on the release of iodine from hydroiodic acid, a test for peroxides, no connection was made between his discovery and any other vitamin activity. What Price found was the activity of vitamin K2, formed in mammary glands from phylloquinone, vitamin K1, found in abundance in rapidly growing green grass [3]. No connection was made between the anticoagulation activity of K1 and the mineral-directing activity of vitamin K2 until the modern research era.
\n
Because of the way vitamin K was discovered for its coagulation function, it was assumed that this was its only function for many years. The Recommended Daily Allowance (RDA) for vitamin K is based on its coagulation function. Though both phylloquinone (phyllo—from plants) and menaquinones support coagulation, as we explore in this chapter, there are clear differences between the functioning of phylloquinone and the menaquinones, and they are not fully interchangeable.
\n
This chapter is a review of vitamin K2 research in the area of cardiovascular health, especially dealing with arterial calcification. It is organized in a loose chronological order, following the themes of the research as the field matured. First, there were observations about dietary intake of K1 and K2 and health outcomes, forming hypotheses to be tested further. Associations were discovered at this stage. Harmful observations with warfarin-type drugs, which are vitamin K antagonists, were seen early on in the research cycle as well. Hypotheses were then explored with animal studies, looking for mechanisms and biomarkers—to help get endpoints that were quicker to develop than mortality and disease. Then came the rise of biomarker studies, using markers for vitamin K status (dp-ucMGP), as well as markers for risk factors, such as arterial calcification, pointing to disease outcomes. As the science matured even further, intervention studies related to K2 and biomarker changes emerged. The final stage is now emerging with intervention studies looking not just at biomarkers but disease outcomes, thus tying all of the research together.
\n
\n
2. Observational studies of dietary vitamin K intake and health outcomes
\n
Observational studies help form hypotheses by finding associations between factors that may or may not be related to the health outcome of interest. One of the early population-based studies in the 1990s examined the vitamin K status of 113 postmenopausal women [4]. Dietary intake of vitamin K was assessed along with examinations for the presence or absence of aortic calcified lesions. Blood samples were assayed for osteocalcin, a vitamin K-dependent protein that is responsible for proper deposition of minerals in bone tissue. It was thought that some forms of osteocalcin might be a marker for vitamin K status. The first type had low affinity for hydroxyapatite, while the second had high affinity. Women with calcified lesions (n = 34) had a lower intake of total vitamin K as well as a higher amount of low-affinity osteocalcin. Together these results indicated that these women had impaired vitamin K status that might be related to their atherosclerotic lesions.
\n
A groundbreaking study took place in the Netherlands which changed the way vitamin K2 was thought of afterward. First, a very careful survey of foods eaten in the Netherlands was carried out by interview-based dietary intakes of over 5400 people, guided by a validated food frequency questionnaire (FFQ). For many animal-based foods, the quantitation of vitamin K2 had not been done, so this was carried out and reported as well. The mean intake of K1 and K2, respectively, varied from 124 and 9.3 µg/day in the lowest quartile to 375 and 45 µg/day in the upper quartile [5]. A report of health outcomes from the Rotterdam Study in 2004 from 4800 of these subjects revealed that even though vitamin K2 was a minor part of the total vitamin K intake, only K2 and not K1 intake was associated with a lower risk of disease [6]. For people in the upper third of intakes of K2 compared to the lowest third, there were decreases in relative risks of coronary heart disease (CHD) mortality (57%), all-cause mortality (26%), and severe aortic calcification (52%). Even though intakes of K2 were only about 10% as much as the amounts of K1, their effect on cardiovascular disease was greater. Cheese was the primary source of menaquinones in this cohort in the Netherlands, not exactly highly regarded as a heart healthy food. This fact made confounding by other “healthy” nutrients less likely and made the results more robust.
\n
Similar results have been seen in a second study, from the Prospect-EPIC cohort, also from the Netherlands [7]. About 16,000 women aged 49–70 were followed for 8 years. Vitamin K1 and K2 intakes were estimated from a FFQ . Vitamin K2 intake varied from <20 to >36 µg/day across quartiles. For every increase of 10 µg of K2, there was a 9% reduction in hazard ratio of risk of CHD, with the effects coming mainly from menaquinone subtypes MK-7, MK-8, and MK-9. There was no association between intake of K1 and CHD, as seen in the Rotterdam Study.
\n
Two large cohort studies have been analyzed for associations between vitamin K intake and CHD. When the Nurses’ Health Study (NHS) cohort was analyzed for an association between dietary vitamin K intake and cardiovascular outcomes, it was found that K1 intake was associated with a 21% decrease in multivariate relative risk of total CHD [8]. The association was attenuated by adjustments for other dietary factors and lifestyle patterns, so that it was not apparent to the authors whether the results were due to vitamin K1 or that K1 was just a marker for a lifestyle pattern associated with a high intake of K1. Median intakes of K1 for the lowest and highest quintiles were 87 and 300 µg/day for the NHS cohort. In another large cohort, the Health Professionals’ Follow-up Study, there was a decrease in the relative risk of total CHD across increasing quintiles of vitamin K1 intake. However, when the results were adjusted for lifestyle and other dietary factors, the trend was no longer significant [9]. Neither of these large cohorts reported dietary intakes of K2, perhaps because the database for menaquinone concentrations in the USA was not complete at that time, nor is it fully available at the time of writing this chapter (only partial data are available on MK-4 but none on higher menaquinones), 17 years after such data were obtained for the Rotterdam Study [5]. The negative results from these cohorts for vitamin K1 and CHD only reinforce just how striking the results were from the Dutch studies for vitamin K2. The findings from the Netherlands were not expected or anticipated by many.
\n
The question of whether vitamin K intake is related to arterial calcifications has been probed in two observational studies. In a cross-sectional study of 1689 women, dietary intakes of vitamin K1 and K2 were estimated with an FFQ, and standard screening mammograms were assessed for the presence of breast arterial calcifications [10]. Unadjusted results showed an inverse association between intake of vitamin K2 and breast arterial calcifications, but adjustments for aging, smoking, diabetes, and dietary factors made the association no longer significant. Adjustment for diabetes may have been unwise, as vitamin K2 intake has also been shown to reduce the risk of diabetes among 38,000 Dutch men and women in the Prospect-EPIC cohort mentioned previously [11]. So, this adjustment may have attenuated the results enough to make the association no longer statistically significant.
\n
In another cross-sectional study, 564 postmenopausal women were examined for an association between coronary calcifications and intake of vitamins K1 and K2 [12]. Women were chosen from the Prospect-EPIC cohort study. In this cohort, cheese contributed 54%, milk products contributed 22%, and meat contributed 15% of the K2 intake. The mean intake of K2 ranged from 18.0 ± 4.5 to 48.5 ± 9.0 in the lowest and highest quartiles, respectively. Examinations found that 62% of the women had coronary calcifications. In the model adjusted for age and cardiovascular risk factors, increased menaquinone intakes were associated with a decreased calcification prevalence ratio of 0.80 (95% CI: 0.65–0.98), comparing highest to lowest quartile.
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A more recent observational study reported findings contrary to those found in the Prospect-EPIC cohort and the Rotterdam Study. The PREDIMED cohort is a Spanish study to examine the effect of adoption of the Mediterranean Diet on cardiovascular, cancer, and all-cause mortality. The intakes of vitamins K1 and K2 were estimated by FFQ, and endpoints of cardiovascular, cancer, or all-cause mortality were tracked for a median follow-up of 4.8 years. Energy-adjusted intakes of vitamins K1 and K2, respectively, ranged from 170 and 18.4 µg/day in the lowest quartiles for each vitamin to 626 and 57.5 µg/day in the upper quartiles [13]. People in the upper quartile consumed about twice as many vegetables, especially leafy greens, as those in the lowest quartile. The upper quartile of vitamin K intake in this cohort adopting the Mediterranean Diet was substantially higher than seen in the other observational studies of other European or American cohorts. No protective effects for higher intakes of menaquinones were seen in this cohort for cardiovascular mortality, cancer mortality, or all-cause mortality. However, high intakes of phylloquinone lead to a reduced hazard ratio of 0.54 and 0.64 for cancer mortality and all-cause mortality. It is possible that enough vitamin K1 and other plant-based protective nutrients such as folate, vitamin C, fiber, potassium, and magnesium were supplied by the diet that even those participants who had low intakes of menaquinones were still not at an elevated risk compared to other subjects in the PREDIMED cohort. Participants who increased their intake of either vitamins K1 or K2 or both during the course of the study experienced decreased risk of cardiovascular mortality (K1 only), cancer mortality, and all-cause mortality. The main conclusion from this observational study perhaps is that eating plants is good for you, and the Mediterranean Diet is generally beneficial, as seen in another report from this cohort [14].
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3. Vitamin K antagonist studies
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Another line of evidence that led to the discovery of the role of menaquinones was the effect of blood thinning drugs such as warfarin and coumarin. While this class of drugs has been very helpful in preventing strokes in the short term, it has also caused damage long term, as people are often prescribed blood thinners for many years. In 1998, it was reported by Price et al. [15] that warfarin caused calcification of the elastic lamellae in rat arteries and heart valves within a period of 2 weeks, with increasing intensity each week. Vitamin K1 was given concurrently to maintain normal blood coagulation. At the time, menaquinone was not even mentioned in the article, not even in the discussion. The discovery of importance was that warfarin had negative side effects for arterial calcification that were not counteracted by vitamin K1.
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This discovery nearly coincided in time with work on an MGP-deficient mouse model. Matrix γ-carboxylation protein, or matrix Gla protein (MGP), was originally discovered in bone tissue but is actually expressed in many tissues of the body, including vascular smooth muscle cells and chondrocytes in cartilage. MGP requires the activation by vitamin K in order to bind calcium ions and prevent crystallization of calcium. These MGP-deficient mice developed normally to term but died within 2 months as a result of extensive arterial calcification, which led to blood vessel rupture [16]. Also seen was the inappropriate calcification of cartilage, including the growth plate of bones. This MGP-deficient mouse model clearly showed that MGP has a central, active role in preventing calcifications of arterial walls and also of cartilage. This research coupled together with the warfarin-caused calcification pointed to a central role for MGP in controlling arterial calcification.
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Further work on the interrelationship between vitamin K1 and K2 was spurred on by feeding studies in rats. When rats were made vitamin K deficient, then fed only K2 as MK-4, they accumulated MK-4 especially in the pancreas, aorta, fatty tissues, and brain. Liver and serum levels of MK-4 were low. When vitamin K–deficient rats were fed only K1, they accumulated K1 in the liver, heart, and fatty tissues, and they also accumulated MK-4 in the same way as the rats that were fed MK-4, indicating that there was conversion from phylloquinone to MK-4 [17]. So, with a warfarin-rat model that was able to induce arterial calcification and knowing that there were differences between K1 and K2 distributions in the rats and that K2 prevented heart disease in the Rotterdam Study, Spronk and coworkers set out to see how to prevent arterial calcification [18]. When warfarin-treated rats were fed K1, the rats got arterial calcification, as shown before [15], even at the highest tested dose of K1. But when the warfarin-treated rats were fed K2 as MK-4 or K1 together with MK-4 simultaneously, the arterial calcification was prevented. The picture was becoming clearer. Further studies have shown that in this rodent model warfarin treatment not only causes arterial calcification but functionally augments aortic peak velocity, aortic valve-peak gradient, and carotid pulse-wave velocity [19].
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The work in rats spurred investigators to look at the effect of anticoagulants in people. In one study, aortic heart valves were examined that had been replaced during routine surgery. Some patients received preoperative marcoumar treatment, for between 16 and 35 months, with a mean of 25 months. When compared with patients who did not have any blood thinner treatment, there was about twice as much calcification on the valves from patients who had received the marcoumar [20]. The mean calcified area on the valve went from 16% in the untreated group to 37% in the anticoagulant group. In a cross-sectional study, coronary artery calcium scores and valvular calcium scores were compared between patients on long-term use of anticoagulants and patients without any anticoagulant therapy [21]. The Agaston calcium scores were about double in the anticoagulant treatment group, indicating that the effects of anticoagulants seen in mice and rats are also present in people, even when the treatment was only for a couple of years.
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These initial results have been confirmed by further studies. Rennenberg et al. [22] examined 19 patients younger than 55 years of age who had used coumarins for more than 10 years but did not have other cardiovascular risk factors. These patients were compared with 18 matched healthy controls. When they examined femoral arteries, they found the coumarin users had 8.5 times the chance of having arterial calcification compared to the healthy controls. Fourteen of 19 coumarin users, but only 4 of 18 controls had femoral arterial calcifications. Another cross-section examination of low-risk atrial fibrillation patients found that both age and use of oral anticoagulants were related to increased coronary calcium score [23]. And as length of time using the anticoagulants increased, the coronary calcium score also increased, going from 53 ± 115 for no use to 90 ± 167 for 6–60 months, and to 236 ± 278 for >60 months of use. These findings were also confirmed in a series of 133 oral anticoagulant users matched by age, gender, and Framingham cardiovascular risk score [24]. Agaston calcium scores increased from 79.6 ± 159.8 for use of 2.5 ± 1.5 months, to 142.4 ± 306.0 for 18.7 ± 8.8 months, to 252.5 ± 399.3 for 86.4 ± 47.1 months of use.
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In women undergoing screening mammography who took warfarin, breast arterial calcifications were also more common with increasing length of warfarin treatment [25]. Prevalence of breast arterial calcifications increased from 25.0% for <1 year of therapy to 74.4% for >5 years of therapy. So, these calcifications can appear in peripheral tissues as well, not just in the aorta. To show this peripheral effect further, and in men, after completing the breast arterial calcification study, Han and O’Neill examined radiographs of ankles and feet, retrospectively, and checked records for warfarin use prior to the x-ray [26]. They found a significant increase, from 19% to 38% prevalence, in peripheral arterial calcifications in people who had been using warfarin for at least 5 years prior to their x-ray. While these drugs could be termed “anticoagulants,” the preferred term for many of these authors is vitamin K antagonists, for this is their mode of action.
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Calcification of arteries had originally been thought of as a one-way process, without reversibility, similar to the thinking about coronary plaque. However, just as regression can be seen of atherosclerotic plaques [27], so calcification of arteries, too, is a dynamic process. Using the warfarin-treated rat as a model for arterial calcification, Schurgers et al. [28] first fed rats for 6 weeks on the diet to induce calcification. Then the warfarin treatment was stopped and rats were fed normal levels of K1, or high levels of K1 or K2 (as MK-4). Normal levels of vitamin K1 continued to progressively increase calcification, but both forms of vitamin K at high doses reversed arterial calcification by about 50%. Vitamin K1 does not work as long as warfarin is present, as it inhibits the conversion of K1 into MK-4. But when the warfarin treatment is stopped, this research clearly showed that this calcification process could be reversed by high doses of vitamin K, especially K2.
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4. Biomarker research studies
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One difficulty in this field of research is determining the functional vitamin K status of an individual. A blood test of vitamin K levels is not sufficient. The amount of vitamin K in the blood is very small and generally only reflects the vitamin K1 that was consumed within the last 4 hours or so, as K2 levels are too low to assay in blood, and K1 clears from the blood with triglycerides. As research progressed, it became increasingly apparent that there were more functions for vitamin K than originally discovered. Coagulation was only the most immediately obvious function of vitamin K in the liver. But the observation studies and vitamin K antagonist research indicated more functions beyond coagulation, dealing with regulation of calcification throughout the body. McCann and Ames [29] elaborated on this multifunction vitamin, indicating that triage theory helps us understand the distribution of vitamin K to various organs. Triage theory states that the most critical functional needs are met first in the body (coagulation) when there is a shortage of a micronutrient. Then when there is an abundance of the micronutrient, all of the secondary functions important to long-term health are also met.
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For these reasons, and possibly others, functional tests for vitamin K status for these secondary functions beyond coagulation were sought. Osteocalcin, a vitamin K–dependent protein found in bone, can be measured in the circulation as well. The ratio of carboxylated to undercarboxylated or uncarboxylated osteocalcin is one biomarker for functional vitamin K status. However, this applies more to the status of vitamin K as it applies to bones. Since MGP is involved in arterial calcification, assays for determining the concentrations of various forms of MGP were developed [30, 31]. Of the various forms of MGP, the dephosphorylated, uncarboxylated form has been most closely related to arterial calcification. Among coumarin users an elevated dp-ucMGP level was found compared to controls (1439 ± 481 pM vs. 299 ± 163 pM, respectively) [22]. In a cohort of 101 chronic kidney disease patients, the level of dp-ucMGP increased with increased severity of the disease [32]. Plasma dp-ucMGP was also independently associated with aortic calcification, and a concentration greater than 921 pM was a predictor of all-cause mortality in a crude analysis.
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What about when people on dialysis are also taking oral anticoagulants? Among 160 hemodialysis patients in Belgium, the 23 who were treated with anticoagulants had much higher circulating concentrations of dp-ucMGP, 5604 pM (interquartile range: 3758, 7836 pM) and 1939 pM (interquartile range: 1419, 2841pM) for the anticoagulant treated and non-treated groups [33].
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In a study of 147 patients with symptomatic severe calcific valvular aortic stenosis, the levels of dp-ucMGP were associated with cardiac function and long-term mortality in multivariate analysis [34]. Increasing severity of disease was related to dp-ucMGP concentrations in a study of 179 patients with chronic heart failure [35].
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The dp-ucMGP assay was checked for correlation with vitamin K status and coronary artery calcification in a study of older adults without cardiovascular disease [36]. While the assay did correlate well with plasma phylloquinone, uncarboxylated prothrombin, and serum uncarboxylated osteocalcin, there was no association between dp-ucMGP levels and coronary artery calcification. Shea and coworkers [36] presented data that are not consistent with the other reports on this assay. Perhaps the assay works better for much higher levels of dp-ucMGP, such as found in disease states. This study looked at older adults without clinical cardiovascular disease, whose levels of dp-ucMGP were much lower than subjects with cardiovascular disease (CVD). As suggested by the authors, the coronary artery calcification analyzed in this report may have been more in the intimal layer, rather than in the medial layer, where MGP has a greater role [28]. A more recent study involving 200 health women found a borderline statistically significant relationship between dp-ucMGP and coronary artery calcification, as well as a strong relationship between dp-ucMGP and vitamin K status (ratio of carboxylated osteocalcin) [37]. The results in [36] appear to the exception, as there is a consistent relationship between dp-ucMGP, vitamin K status, and health outcomes involving arterial calcification in all of the other studies examined.
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Other studies have generally found that the biomarker dp-ucMGP does correlate with vitamin K status and disease outcomes related to arterial calcification. In the EPIC-NL cohort, 518 participants were identified as diabetic at baseline [38]. After 11.2 years of follow-up, incidence of CVD was significantly associated with baseline concentrations of dp-ucMGP, but not other species of MGP. The hazard ratio per standard deviation (HRSD) of dp-ucMGP for all CVD was 1.21 (95% CI 1.06–1.38), for peripheral artery disease HRSD = 1.32 (95% CI 1.07–1.65), and for heart failure HRSD = 1.85 (95% CI 1.42–2.17). The prospective Longitudinal Aging Study, Amsterdam (LASA) examined 577 people aged >55 years who were free of CVD at the baseline [39]. There were 40 incident cases of CVD during the 5.6 years of follow-up. For the highest tertile compared to the lowest tertile of dp-ucMGP, there was a hazard ratio of 2.69 (95% CI 1.09–6.62) for being diagnosed with CVD. The carboxylated form of MGP was not related to risk of CVD.
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Two Czech Republic prospective studies have examined the usefulness of the dp-ucMGP as a biomarker to predict cardiovascular mortality. From the EUROASPIRE III and EUROASPIRE-stroke surveys, 799 patients were examined who had already experienced a myocardial infarction, coronary revascularization, or first ischemic stroke. After a median follow-up of 5.6 years, 159 patients died. In the fully adjusted model, the patients in the highest quartile of dp-ucMGP (≥977 pM) had higher risk of all-cause and cardiovascular mortality, HRR 1.89 (95% CI 1.32–2.72) and 1.88 (95% CI 1.18–2.61), respectively [40]. For those subjects in the upper quartile of dp-ucMGP who also had heart failure, indicated by an elevated circulating brain natriuretic peptide level >100 ng/L, mortality risk was further increased, HRR 4.86 (95% CI 3.15–7.49) [41]. In a random sample from the general population from the Czech post-MONICA study, Mayer et al. [42] found that aortic stiffness, as measured by pulse wave velocity, was related to vitamin K status. Compared to the lowest quartile, the upper quartile of dp-ucMGP (≥671 pM) has an increased odds ratio of 1.73 (95% CI 1.17–2.5).
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5. Intervention studies
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One of the first intervention types was to confirm the utility of various species of MGP as biomarkers for vitamin K status. If you improve someone’s status by oral supplementation, the biomarker should reflect this improvement in a dose-dependent manner. So, in 2012, Dalmeijer and coworkers [43] reported a randomized, double-blind placebo-controlled trial (RCT) of 60 people taking 0, 180, or 360 µg/day of vitamin K2 as menaquinone 7 (MK-7) for 12 weeks. Assays were performed for three different species of MGP: desphospho-uncarboxylated MGP (dp-ucMGP), desphospho-carboxylated MGP (dp-cMGP), and total uncarboxylated MGP (t-ucMGP). Vitamin K status was also measured using the ratio of uncarboxylated to carboxylated osteocalcin. (Note that the research field on the role of vitamin K2 in bones matured earlier than the field of cardiovascular effects of K2, so osteocalcin was well established as a vitamin K2 marker by this time.) After 12 weeks of the supplements, the osteocalcin ratio decreased significantly, with a 60% drop at 180 µg dose and a 74% drop at the 360 µg dose. The amount of dp-ucMGP decreased significantly and dose-dependently as well, by 31% and 46% at 180 and 360 µg, respectively. There were no changes in the placebo group, as expected. Changes in other species of MGP (dp-cMGP and t-ucMGP) were not different between placebo and the supplement groups. This study was one of the first intervention trials to validate the usefulness of dp-ucMGP as a biomarker for vitamin K status. Observational studies had been carried out, but the intervention studies took the research one more step toward maturity.
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In the same year, another RCT was reported of 42 Dutch men and women randomized to receive 0, 10, 20, 45, 90, 180, or 360 µg/day of vitamin K2 as MK-7. The ratio of uncarboxylated to carboxylated osteocalcin was determined along with the concentration of dp-ucMGP. The upper three doses (90, 180, and 360 µg/day) increased the carboxylation of osteocalcin and decreased the amount of dp-ucMGP. In these healthy adults aged 18–45, no adverse effects were seen on the generation of thrombin, indicating that coagulation factors were not perturbed by the additional supply of vitamin K2. This is reasonable, for the coagulation factors are generally all carboxylated. Only the extrahepatic vitamin K–dependent proteins seem to suffer when there is a shortage of vitamin K, as explained by the triage theory [29].
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Patients with chronic kidney disease and those undergoing dialysis have been shown repeatedly to suffer with high levels of uncarboxylated vitamin K–dependent proteins and have high levels of arterial calcification as well. (The most deficient group is the same patients taking vitamin K antagonist drugs concurrently.) In order to prepare for a RCT with a disease endpoint of stabilizing or reversing arterial calcification in this patient group, a supplement trial was conducted in the Netherlands with 50 hemodialysis patients [44]. An age-matched healthy control group was selected also for comparisons. The hemodialysis patients were randomized into groups taking 45, 135, or 360 µg/day of vitamin K2 as MK-7 for 6 weeks. Measurements were taken for the levels of uncarboxylated osteocalcin (ucOC), dp-ucMGP, and PIVKA-II. PIVKA-II is a prothrombin liver protein that is only seen in the circulation under situations of severe vitamin K deficiency, such as found in hemodialysis patients. At baseline hemodialysis, patients, compared to healthy controls, had 4.5-fold higher dp-ucMGP levels and 8.4-fold higher uncarboxylated osteocalcin levels. PIVKA-II levels were detectable in 49 of the 50 hemodialysis patients. There was a dose-dependent response to the MK-7 treatment, with the 45 µg dose being little different than a placebo, the 135 µg dose giving 37%, 11%, and 34% changes in dp-ucMGP, ucOC, and PIVKA-II, respectively, which was almost significant, and the 360 µg dose yielding statistically significant changes of 61%, 34%, and 42% decreases in dp-ucMGP, ucOC, and PIVKA-II. This short trial showed both the severity of the vitamin K deficiency in this hemodialysis patient group as well as the effectiveness of a relatively high dose (360 µg/day) of MK-7 in bringing down functional markers of vitamin K deficiency.
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As a follow-up to the Westenfeld Study [44] just reviewed, another larger study with hemodialysis patients was carried out with slightly higher doses, but administered three times a week by a nurse after dialysis [45]. This method was used to increase patient compliance. Doses for the 200 patients were 360, 720, and 1080 µg of MK-7 three times as week for 8 weeks. This works out to equivalent daily doses of 154, 309, and 463 µg/day. After 8 weeks, levels of dp-ucMGP decreased by 17, 33, and 46% in the three dosage groups, respectively. Results here were similar to those in [44], but with less decrease in relative change in dp-ucMGP at the highest dose (46% vs. 61%). However, the absolute differences before and after intervention were greater in [45]. Absolute changes in dp-upMGP in the Westenfeld Study were −404, −730, and −978 pM at 45, 135, and 360 µg/day [44]. In a study by Caluwé and coworkers [45], absolute changes in dp-ucMGP were −566, −962, and −1487 pM for the equivalent daily doses of 154, 309, and 463 µg/day. So, the outcomes were very similar, especially given that the second trial was 8 weeks long rather than just 6 weeks.
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How widespread is extrahepatic vitamin K insufficiency? A cross-sectional sample of 896 healthy individuals showed that dp-ucMGP levels increased with age, staying around 200 pM until about age 40 and then increasing up to over 600 pM for those >70 years of age [46]. Levels of dp-ucMGP decreased in children and adults when given supplemental MK-7, again showing that dp-ucMGP was a biomarker that responded to extrahepatic vitamin K status, and that many adults had less than optimal levels of vitamin K. These levels are not optimal, neither are they as severe as hemodialysis patients, who averaged around 3000 pM but ranged to over 7000 pM in some individuals [44, 45]. Hemodialysis patients who took vitamin K antagonists had a mean dp-ucMGP of about 5600 pM [33]. But the values >600 pM in the >70 age group are close to the range at which excess heart disease mortality occurred in other studies, >977 pM in [40] and >921 pM in [32]. Calcification of arteries takes time and finally takes a toll on the elderly if not protected against through the years.
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In one of the first RCT studies to report a disease endpoint, Knapen and coworkers examined arterial stiffness in 244 women after supplementation for 3 years with 180 µg/day of MK-7 [47]. Previous work by this research group had linked increased levels of dp-ucMGP with arterial stiffness [48]. Compared to the placebo group, dp-ucMGP levels dropped by about 50%. The K2 treatment resulted in improvements in the whole group, but the best results for improving stiffness were seen in those women who started with the worse condition, with a stiffness index β above the median of 10.8. For these women, there were improvements in distention, compliance, distensibility, Young’s Modulus, and the local carotid pulse wave velocity. Not all became normal, as acute phase markers interleukin-6, C-reactive protein, and tumor necrosis factor-α remained abnormal as well as the markers of endothelial dysfunction vascular cell adhesion molecule and E-selectin.
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A Polish RCT study examined disease endpoints for vascular calcification and progression of atherosclerosis in 42 women who had chronic kidney disease but were not undergoing dialysis [49]. The women were split into three groups followed for 270 days: one taking 90 µg/day of MK-7 (K), one group taking 90 µg/day of MK-7 plus 10 µg/day of vitamin D as cholecalciferol (K+D), and one taking only 10 µg/day of vitamin D (D). The results were that the intervention slowed the progression of atherosclerosis but did not significantly slow the increase in coronary artery calcium score. The reason for this lack of success is in the dose of MK-7 used. As noted in the studies by Westenfeld et al. [44] and Caluwé et al. [45], a daily dose of around 360 µg is needed to significantly reduce dp-ucMGP. Changes in dp-ucMGP were reported to be significant in this Polish trial, but actual change was from 1077.1 ± 507.7 to 961.5 ± 506.7, or a change of only 115.6 pM. While this change may have been statistically significant, it was clinically irrelevant. This study also reveals why it is important to develop research stepwise to ensure that interventions will be successful. If the treatment is not expected to yield a large change in biomarker studies, how would it yield a successful clinical result?
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A rationale and study protocol has been published for the VitaK-CAC trial [50]. For this 2-year trial, the intervention will be 360 µg/day of MK-7. Patients with coronary artery disease will be monitored for coronary artery calcification as the primary endpoint. Secondary endpoints will be arterial structure and function. This study appears to be well designed to yield good results, as long as the arterial calcification seen in coronary arteries is susceptible to the MGP mechanism of action. Nutrients have a way of working in complimentary fashion, if not synergistically. The best chance for successful intervention is to use all of the known tools available, which is discussed in the section on plant-based diets below.
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6. Prostate health and vitamin K2
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While the focus of this chapter has been on arterial calcification and cardiovascular health, it has come to the attention of this author that there is evidence that supports a hypothesis that poor prostate health is not a hormone issue, but a cardiovascular issue [51]. The first piece of evidence comes from interventional radiologists Dr. Gat and coworkers, who were initially working on reversing infertility in men by relieving varicoceles, or varicose veins in the pampiniform venous plexus. They discovered that varicose veins in the internal spermatic vein, which normally returns blood from the testes to the kidneys, prevented normal blood flow. The one-way valves had failed in this vein, possibly causing the varicose vein, or as part of the process of forming varicose veins—the exact mechanism is debated. So instead of normal blood flow, the blood flowed retrograde through the prostatic veins. When testosterone levels were measured near the prostate gland in 12 infertile men with varicocele, the mean concentration was 3632 pmol/l compared to 27.33 pmol/l in the serum, or about 130 times higher [52]. By occluding the internal spermatic vein, Dr. Gat was able to relieve the physical pressure due to the elevated blood pressure caused by the height of the column of blood sitting in the internal spermatic vein and also made a pathway through normal venous pathways for blood to drain away from the testes without retrograde flow past the prostate. This venous occlusion surgery led to relief of benign prostatic hyperplasia (BPH), and possibly prevention of prostate cancer as well [52].
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Varicose veins and destruction of the one-way valves in the internal spermatic vein were the direct cause of BPH, but what causes varicose veins? Work by Cario-Toumaniantz and coworkers [53] on the differentially expressed genes and gene products in varicose vein tissue showed an overexpression of genes involved in extracellular remodeling, including matrix Gla protein. Smooth muscle cells were seen proliferating in varicose vein tissue with high expression of MGP, particularly the uncarboxylated form of MGP. Overexpression of MGP and proliferation of smooth muscle cells have been seen before, reported by Price and coworkers investigating the effects of warfarin on arterial calcification in rats [15], and by Schurgers and coworkers reporting the reversal of warfarin-induced arterial calcification in rats [28]. In areas of calcification of arteries, there is proliferation of smooth muscle cells and increased expression of uncarboxylated MGP, similar to what was seen in varicose vein tissue [53]. It is likely then that vitamin K is involved in the mechanism by which varicose veins form, just as it has been implicated in the formation of arterial calcifications. When varicose vein tissue culture was treated with warfarin, mineralization increased, which could be inhibited by the inclusion of vitamin K in the culture media [53], indicating a direct role for vitamin K in the prevention of varicose veins.
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In addition to this evidence from cellular biology, evidence from a prospective observational study showed an association between intake of vitamin K2 and poor prostate health manifested as prostate cancer. There was a significant association between menaquinone intake and advanced prostate cancer in the EPIC-Heidelberg cohort [54]. A nested case-control follow-up study also found an association between the ratio of undercarboxylated osteocalcin to carboxylated osteocalcin and high-grade prostate cancer and advanced prostate cancer [55]. Neither of these reports found a connection with vitamin K1 intake. Further evidence comes from a retrospective study of warfarin use and clinical stage of prostate cancer at diagnosis [56]. While some of the evidence for intermediate or short-term use of warfarin is conflicting, the comparison between those men who had used warfarin for at least 4 years in the 5 years before prostate cancer diagnosis and nonusers of warfarin showed an odds ratio of 2.2 (95% CI 1.03–4.81) of poor prognosis disease. This would seem to agree with the hypothesis that vitamin K antagonists would increase the possibility of forming varicoceles, leading to poor prostate health. But there could be other mechanisms of action as well.
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At this point, the role of vitamin K2 in prostate health is a good hypothesis but needs further confirmation by interventional radiologists and other researchers before the link between prostate health and cardiovascular function, especially the role of vitamin K2 plays, is certain.
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7. Vitamin K2 and a plant-based diet?
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Reversal of atherosclerosis by a plant-based diet has already been mentioned in this chapter [27]. Dr. Esselstyn has also shown that a plant-based diet very low in fat can reverse coronary artery disease [57]. Of 198 subjects in the lifestyle intervention study, 177 were adherent to the program while 21 formed a control group of non-adherent comparison subjects. There was reversal of angiographic-verified blockages in 39 adherent subjects. Disease progression occurred in 4 (2.3%) adherent subjects, but in 11 (52.4%) of the non-adherent subjects. Coronary artery calcification was not measured.
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There is abundant evidence that increased consumption of fruits and vegetables in conjunction with exercise and a healthy lifestyle is beneficial for cardiovascular health and lower cardiovascular mortality. Healthy diets have been reported to lower cardiovascular mortality risk by about 30–40% [14, 58, 59]. When combined with other lifestyle factors, the risk plummets to about 20% or less compared to the least healthy fraction of the population [60–63].
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The point here is that all available resources should be used to counter the disease process and to promote healthy aging. While vitamin K2 is a valuable nutrient that is generally in short supply in the global diet, the context of the entire diet must be kept in mind. The best results will be obtained by a full complement of healthy foods. Population studies have shown that even 40–50 µg/day of menaquinones from the diet is associated with cardioprotection [6, 7] and lower risk of advanced prostate cancer and lung cancer [54, 55, 64].
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Is vitamin K2 compatible with a plant-based diet? While most of the common sources of menaquinones are cheese, fermented dairy products, eggs, and meats, there are plant sources as well. While these are animal products, judicial selection could be used to maximize K2 intake without consuming a large amount of any animal-based foods. Natto is a well-known Japanese food that is very rich in MK-7, though not very popular outside of Japan. The menaquinone in natto is made by fermentation with Bacillus subtilis var. natto. Fermented vegetables such as sauerkraut contain a small amount of menaquinones as well. By selecting probiotic bacteria based on their production of menaquinones, the amount of vitamin K2 from a serving of fermented vegetables could be significant. More product development is needed in this area.
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8. Research directions and priorities
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The research on vitamin K2 and cardiovascular health has come a long way, going from observational studies of populations and warfarin studies, to developing biomarkers, finding effective dosage schedules, and begin carrying out RCT studies examining disease endpoints. Very few disease endpoints have been reported at this time, but several should be completed in the next few years. Diseases are multifaceted, so the solutions should likewise be multifaceted. Trying to reverse a complex disease with a single nutrient has generally been unsuccessful. It is likely that the best success will be found when vitamin K2 is used in the context of a whole food plant-based diet that contains some dietary source of vitamin K2, along with supplements to reverse disease damage when appropriate.
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One of the major benefits seen by Dr. Weston Price in the 1930s was the prevention and reversal of dental caries using vitamin K2 [2]. This could be a very fruitful area of research that is untapped at this point. Mental health effects of vitamin K2 are likely as well, as the brain contains a significant concentration of K2. Varicose veins in general and prostate health in particular should be studied in light of the K2 research presented here in this chapter. Mechanisms of the function of MGP should be worked out along the way as well. Identification of the function of other vitamin K–dependent proteins is still lacking. There is a gamma-carboxylation–rich protein (GRP) that is quite small yet has 16 carboxylation sites and is highly expressed in cartilage. Its exact function is still unknown. So, there is work that can be done at the molecular level as well as at the public health level in furthering our understanding of vitamin K2.
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Conflict of Interest
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Michael Donaldson is a research scientist at the Hallelujah Acres Foundation for investigations pertaining to the Hallelujah Diet. Funding for this research has been provided by Hallelujah Acres, Inc.
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\n\n',keywords:"menaquinone, menaquinone-4 (MK-4), menaquinone-7 (MK-7), cardiovascular, calcification, prostate, plant-based diet",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/50916.pdf",chapterXML:"https://mts.intechopen.com/source/xml/50916.xml",downloadPdfUrl:"/chapter/pdf-download/50916",previewPdfUrl:"/chapter/pdf-preview/50916",totalDownloads:3677,totalViews:622,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:24,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"October 27th 2015",dateReviewed:"March 31st 2016",datePrePublished:null,datePublished:"March 22nd 2017",dateFinished:"June 2nd 2016",readingETA:"0",abstract:"Vitamin K was originally discovered as a blood coagulation factor. But observations regarding intakes in populations and health outcomes lead to a deeper understanding of the differences between vitamins K1 and K2. Studies of warfarin-treated rats and MGP -deficient mice led to understanding the central role of MGP in controlling calcification of arteries. A sensitive biomarker assay was then developed, based on a particular species of matrix γ–carboxylation protein OR matrix GLA protein (MGP). Warfarin therapy in people, especially those suffering from chronic kidney disease, was found to cause the highest level of this biomarker desphospho-uncarboxylated MGP (dp-ucMGP). Intervention studies with vitamin K2 brought down levels of dp-ucMGP and also led to relief of some disease endpoints. The process of varicose vein formation includes a role for vitamin K, implicating a lack of vitamin K in the development of varicoceles, which leads to benign prostate hyperplasia. It is likely that much good will be accomplished using vitamin K2 in interventions. Complex, multifaceted diseases will not be treated by single-nutrient solutions. The best interventions will be those which combine vitamin K2 treatment with a healthy diet rich in fruits and vegetables, combined with a healthy lifestyle.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/50916",risUrl:"/chapter/ris/50916",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing"},signatures:"Michael S. Donaldson",authors:[{id:"180516",title:"Dr.",name:"Michael",middleName:null,surname:"Donaldson",fullName:"Michael Donaldson",slug:"michael-donaldson",email:"mdonaldson@hacres.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Observational studies of dietary vitamin K intake and health outcomes",level:"1"},{id:"sec_3",title:"3. Vitamin K antagonist studies",level:"1"},{id:"sec_4",title:"4. Biomarker research studies",level:"1"},{id:"sec_5",title:"5. Intervention studies",level:"1"},{id:"sec_6",title:"6. Prostate health and vitamin K2",level:"1"},{id:"sec_7",title:"7. Vitamin K2 and a plant-based diet?",level:"1"},{id:"sec_8",title:"8. Research directions and priorities",level:"1"},{id:"sec_9",title:"Conflict of Interest",level:"1"}],chapterReferences:[{id:"B1",body:'Dam H. The antihaemorrhagic vitamin of the chick. Biochem J. 1935 Jun;29(6):1273–85.'},{id:"B2",body:'Price WA. Nutrition and physical degeneration. 6th edition. New Canaan, Conn: Keats Pub; 2003. 524 p.'},{id:"B3",body:'Masterjohn C. On the trail of the elusive X-factor: Vitamin K2 revealed. Wise traditions in food, farming and the healing arts [Internet]. 2007 [cited 2016 May 17]. Available from: http://www.westonaprice.org/health-topics/abcs-of-nutrition/on-the-trail-of-the-elusive-x-factor-a-sixty-two-year-old-mystery-finally-solved/'},{id:"B4",body:'Jie K-SG, Bots ML, Vermeer C, Witteman JCM, Grobbee DE. 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Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women. J Nutr Biochem. 2013 Apr;24(4):624–8.'},{id:"B38",body:'Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WMM, Boer JMA, et al. Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2013 Nov 1;36(11):3766–71.'},{id:"B39",body:'van den Heuvel EGHM, van Schoor NM, Lips P, Magdeleyns EJP, Deeg DJH, Vermeer C, et al. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas. 2014 Feb;77(2):137–41.'},{id:"B40",body:'Mayer O, Seidlerová J, Bruthans J, Filipovský J, Timoracká K, Vaněk J, et al. Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease. 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Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb 1;59(2):186–95.'},{id:"B45",body:'Caluwé R, Vandecasteele S, Vlem BV, Vermeer C, Vriese ASD. Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant. 2014 Jul 1;29(7):1385–90.'},{id:"B46",body:'Theuwissen E, Magdeleyns EJ, Braam LAJLM, Teunissen KJ, Knapen MH, Binnekamp IAG, et al. Vitamin K status in healthy volunteers. Food Funct. 2014 Feb;5(2):229–34.'},{id:"B47",body:'Knapen MHJ, Braam LAJLM, Drummen NE, Bekers O, Hoeks APG, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial. Thromb Haemost. 2015 Feb 19;113(5):1135–1144.'},{id:"B48",body:'Pivin E, Ponte B, Pruijm M, Ackermann D, Guessous I, Ehret G, et al. 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Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment. Andrologia. 2008;40(5):273–81.'},{id:"B53",body:'Cario-Toumaniantz C, Boularan C, Schurgers LJ, Heymann M-F, Le Cunff M, Leger J, et al. Identification of differentially expressed genes in human varicose veins: involvement of matrix Gla protein in extracellular matrix remodeling. J Vasc Res. 2007;44(6):444–59.'},{id:"B54",body:'Nimptsch K, Rohrmann S, Linseisen J. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European prospective investigation into cancer and nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008 Apr;87(4):985–92.'},{id:"B55",body:'Nimptsch K, Rohrmann S, Nieters A, Linseisen J. 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Healthy eating and lower mortality risk in a large cohort of cardiac patients who received state-of-the-art drug treatment. Am J Clin Nutr. 2015 Dec 1;102(6):1527–33.'},{id:"B60",body:'Chiuve SE, Fung TT, Rexrode KM, Spiegelman D, Manson JE, Stampfer MJ, et al. Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women. J Am Med Assoc. 2011 Jul 6;306(1):62–9.'},{id:"B61",body:'Chiuve SE, McCullough ML, Sacks FM, Rimm EB. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation. 2006 Jul 11;114(2):160–7.'},{id:"B62",body:'Ford ES, Bergmann MM, Kröger J, Schienkiewitz A, Weikert C, Boeing H. Healthy living is the best revenge: findings from the European prospective investigation into cancer and nutrition-potsdam study. Arch Intern Med. 2009 Aug 10;169(15):1355–62.'},{id:"B63",body:'Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Lifestyle factors on the risks of ischemic and hemorrhagic stroke. Arch Intern Med. 2011 Nov 14;171(20):1811–8.'},{id:"B64",body:'Nimptsch K, Rohrmann S, Kaaks R, Linseisen J. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European prospective investigation into cancer and nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2010 Mar 24;91(5):1348–1358.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Michael S. Donaldson",address:"mdonaldson@myhdiet.com",affiliation:'
Research Director, Hallelujah Acres, Zillah, WA, USA
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1. Introduction
TLD method is considered an important technique as it can store radiation in trap centers for long period. Glow peaks of thermoluminescence dosimeters are later measured and discussed based on some models related to the physical changes in the band structure of dosimeter because of ionizing radiation exposure. A wide range of substances exhibits thermoluminescence (TL) phenomena after being exposed to nuclear radiation such as activated LiF and CaSO4. Thermoluminescent dosimeter (TLD) emits light when heated up after being irradiated. Due to this special property, TLD could be used as a radiation dosimeter. TLD has many advantages and sensitive to different types of radiation. A dosimeter of higher TL response to thermal neutrons is most commonly used in mixed radiation fields (neutron and gamma ray). The sensitivity of TLD to neutrons depends on the detector compound type, environment and neutron energy. For neutron dosimetry purposes, the neutron and gamma ray dose contribution must be separated by using two different detector types of TLD. The first one should be sensitive to gamma and the other should be sensitive to neutrons plus gamma (as LiF-700 and LiF-600) [1, 2].
The response of fast neutrons depends on the cross-section for the interaction in TLD material and the relative TL efficiency, which depends on the linear energy transfer (LET) of the reaction products in the first place. The response to intermediate-energy depends mainly on the cross-section of the reaction, which may take place with the composite material of the TLD.
1.1 TLD applications in neutron and gamma ray dosimetry
Generally, there are three types of TLD used for neutron dosimetry as follow:
1.1.1 Albedo neutron dosimeter
A considerable fraction of intermediate and fast neutrons can be slowed down to epithermal neutron energy and backscattered in the human body, interacting with the sensitive TL material. An albedo neutron dosimeter is a type of neutron monitor and is typically used in the neutron energy range of 0.2 eV to around 0.5 MeV. The slow neutrons interact with TL material, usually through 6Li (n,α) 3H reaction, and the resulting induced charged particles to stimulate the TL material. Recently, some of albedo TLD dosimeters depend on 10B (n, α) 7Li reactions. Because neutron TL sensitive material responds to gamma radiation, and neutrons are accompanied by this gamma radiation, another TLD is usually utilized in conjunction with TLD with a gamma ray.
The neutron albedo dosimeter measures (a) direct fast neutrons, (b) direct thermal neutrons, and (c) albedo neutrons reflected from the body. This type of dosimeter uses Lexan polycarbonate and/or CR-39 foils, as well as two 10B (n, γ) 7Li converters in a cadmium cover, to efficiently measure the three neutron dosage components independently [3, 4, 5]. Fast neutron dose is assessed in CR-39 by counting proton recoil tracks, while thermal neutron dose is determined by counting α particles created during the process. Because the albedo dosimeter has a sensitivity range of 0.3–30 mSv, it is advised that it be used as a backup dosimeter to assist in the assessment of high dose values in the event of accidents or patients receiving neutron therapy.
In another application, the 10B (n, α) 7Li reactions with the backscattered albedo neutrons employed with Electret’s ionization chamber proposed by Seifert et al. [6, 7]. In this chamber, induced 7Li from the ionization of the gas in the chamber worn on the body’s surface in the above reaction instance. Under saturation conditions, produced charge carriers with the corresponding polarity travel to the surface of the electret. As a result, the change in the electrets voltage is a direct measure of albedo neutron fluence and an indirect estimate of primary neutron fluence. In general, the advantages of albedo TLD dosimeter are: they are relatively inexpensive and can be reused, easily fabricated, lightweight to wear, Readout is simple and can be automated, Insensitive to humidity.
While their disadvantages are: Some of TLD exhibit fading, TLD is sensitive to gamma-ray, they must be worm properly or serious errors can be resulted, the measured values of TLD does not give permanent record as the track detectors, their sensitivity is highly dependent on the angle and energy of incidence radiation.
1.1.2 Hydrogenous radiator TLDs
In this type of dosimeters, the fast neutrons knock out protons from hydrogenous material mixed with the phosphor, and the protons dispel their energy in the dosimeter. In this method, the hydrogenous substances are called proton radiators [8]. This technique has demonstrated that TL materials mixed with hydrogenous material can detect fast neutrons, but the sensitivity needs to be improved by one order of magnitude before using in personnel neutron dosimetry.
1.1.3 LET-dependent deep trap TLD glow peaks
The fast neutron interacts directly with the TL material as calcium fluoride (CaF2:Tm) which is commercially called TLD-300. This type has a glow curve with two glow peaks and the peak temperature Tm centered 150 and 250°C, respectively. The higher temperature peak (250°C) has a greater response to the fast neutrons. TLD-300 dosimeter CaF2: Tm (0.35 Mol. %) showed a lower detection limit of about 0.3 mSv from 241Am-Be source.
2. Characteristic of TLD phosphors
2.1 The glow curve
The term “Glow curve” refers to the graph of TL as a function either of temperature or of time as shown in Figure 1.
Figure 1.
TLD glow curve and time–temperature profile (TTP).
Glow curves have the following features:-
The glow curve of a certain phosphor probably best characterizes that phosphor. For example, the appearance of glow peaks only at low temperatures implies that the phosphor loses its stored TL with time, and therefore would be unsuitable for long-term measurements.
A peak at very high temperatures indicates a phosphor that will produce infrared radiation at the temperature necessary to release the TL. This is a problem for the instrumentation.
A glow curve without well-defined peaks makes the selection of the appropriate end for integration difficult. Ideally then, a glow curve should reveal only a single thermoluminescent peak, which occurs at a temperature high enough to ensure room temperature stability but not so high as to present instrumental problems. However, the temperature at which a TL peak appears is quite affected by the heating rate.
The following factors may affect the shape of the glow curve:
2.2 TL sensitivity
The sensitivity of TLD should be evaluated for competitor’s materials to determine the dose linearity, sub linearity or supralinearity behavior of phosphors. The sensitivity and thermal stability of glass samples were found to be dependent on both the starting materials and the method of preparation in Refs. [9, 10, 11, 12, 13].
2.3 Dose rate dependence
TL dosimeters, in general, have demonstrated no dose rate effects over a wide range.
2.4 Stability
TL is the release, in the form of visible light, of energy absorbed from previous irradiation. The rate at which this energy is released is dependent upon the phosphor temperature and increases sharply at a higher temperature. Even though the concept of “glow peak temperature” that temperature at which the maximum of the glow peak occurs, is both useful and easily demonstrated. It should be remembered that a finite rate of loss of stored energy exists even for much lower temperatures. If a phosphor shows an insignificant loss of TL at room temperature, it is said to have good stability.
3. TL kinetics
The physical process leading to the emission of TL from a sample is related in most cases to the traffic of charge carriers, usually electrons and holes, between different imperfection states in the solid sample. Studying the kinetics of the TL process means the investigation of electron–hole transitions between energy states in cases of both the irradiation of the TL sample and the readout processes. Although, in most experimental situations the TL curve consists of several overlapping peaks, it is appropriate to start the discussion by dealing with a single peak to understand the basic process. For most purposes, it is not necessary to assume that the glow curve consists of only one peak. The analysis of a single peak may just be valid if a series of peaks occur, provided that the peak of interest is sufficiently separated from others, either because it appears separately or because we have an efficient method to isolate it from the rest of the curve.
3.1 First kinetics order
If n is the number of trapped electrons in the sample, which is maintained at constant temperature T, n decreases with time t as:
The rate of photon emission, and hence the rate of release of electrons from traps to their rate of arrival at luminescence centers, determine the strength of the TL glow peak [14].
Iα−dndt→I=−Cdndt=nCSexp−EKTE3
Where C is a luminescence efficiency constant.
When the dosimeter is heated with rate β =dT/dt. Then we may write dn/dt as:
It should be noted that I(T) in Eq. (6) dependents on two physical parameters, the activation energy E, and frequency factor S, and the heating rate β. The activation energy is the minimum energy required to release the electrons from their traps. Differentiation of Eq. (6) with respect to the temperature gives:
∂I∂T=noSCexp−EKTexpfT∂fT∂T+expfTexp−EKTEKT2
Where, fT=−Sβ∫Texp−EKTdT
At T=Tm→∂I∂T=o
→sβexp−EKTm=EKTm2E7
where Tm is peak position or the temperature at maximum intensity.
Equation (7) describes the condition of the occurrence of the maximum intensity and the determination of the corresponding temperature, which we call, Tm. The reduction in the second exponential function is faster than the growth in the first exponential function above this temperature, and the product function decreases until the traps are fully depopulated. This accounts for the end of the peak. A theoretical (calculated) glow peak plotted using Eq. (6) is shown in Figure 2. The main feature of the first-order peak is that the asymmetric, is such that at temperatures over Tm, the reduction is faster than the rise at low temperatures.
Figure 2.
Theoretical glow peak plotted using the first kinetics order equation.
The initial concentration no appears in the first kinetics order acts only as a constant multiplying the temperature-dependent factors. In this particular case of the first kinetics order, changing the initial concentration no has no effect on the curve’s form because adjusting the intensity at each temperature has the same proportional effect. Figure 3 shows several glow peaks with different no. One of the aspects of this fact is that Tm is independent of the initial concentration no.
Figure 3.
Glow curves plotted using the first-order kinetics equation for different no.
This appears well in the condition of the Tm described by Eq. (7), where no does not appear in the equation. This property of the independent of Tm on no is specified to the first-order case, and will not occur for most of the other kinetics possibilities [13]. Eq. (7) can be written in the following form:
βEK=STm2exp−EKTmE8
We see that changing the heating rate β must change Tm in a such way that equality still holds. The term Tm2exp−EKT is monotonically increasing with Tm, therefore increasing the rate β will immediately cause Tm to increase. Since Tm2exp−EKT is a very rapidly increasing function of Tm, only a small change of Tm may accompany a large variation in the heating rate β, this variation is usually rather easily observable.
3.1.1 Second kinetics order
One assumption made up by Randall and Wilkins [14] which led to the first kinetics order was that once a charge carrier is thermally elevated into the band, it is bound to recombine rather quickly with an opposite sign carrier trapped in a recombination center. Gralick and Gibson [15] considered another case in which the free carriers may re-trap with equal retrapping recombination probabilities with the further assumption that the concentration of electrons in traps and holes in recombination centers are equal during the entire process. Denoting the total number of traps of the given type (free electrons or holes) by N, they found the kinetics equation:
I=−dndt=SNn2exp−EKTE9
where (S/N) is a constant having units of m3s−1, which we may denote by S′. Then we have
I=−dndt=S′n2exp−EKTE10
where S′ is called “pre-exponential factor” which does not have the same meaning of “frequency factor” as was in the first kinetics order.
where Eq. (12) represents the intensity of a glow peak according to the second kinetics order model. At high temperature, the second decreasing function dominates so that the product function is decreasing. Somewhere between two regions the glow curve, therefore, reaches its maximum. Figure 4 Displays a hypothetical glow peak plotted using Eq. (12).
Figure 4.
Theoretical glow peak plotted using the second-order kinetics equation.
The condition of the maximum is found by setting the derivative of Eq. (12) to zero (dI/dT = zero) [16], then we may find:
Multiply by 1+S´βno∫Tmexp−EKTmdT3 and rearrange, one gets
1+S´βno∫Tmexp−EKTmdT=2KTm2S´noβEexp−EKTmE13
Then Eq. (13) represents the condition of the peak maximum according to the second kinetics order. As can see no appears in the equation and therefore we expect that Tm will depend on no. It can be shown numerically or analytically, that increasing no causes Tm to decrease. An exception to this rule of the shift of a second-order peak with no can be found by Wrzesinska [17], who writes Eq. (10) with S′=Sno. The resulting peak has all the regular features of a second-order peak (e.g., symmetry properties) except one can write S instead of noS’ and thus Eq. (10) turns out to be independent of no. The ensuring Tm is, therefore independent of no. It is not clear, however, what physical circumstances result in S′ being equal to S/no [17]. Other aspects of the dependence of the glow curve on the initial concentration no are paramount importance when we are interested in a TL as a dosimetric tool. In many cases, one associated the initial concentration with the imparted dose and then the dependence of different parts of the glow peak on no is important. In the first kinetics order, since the intensity at each point is multiplied by the same factor while changing no, the total area varies with the same amount so that the total area is proportional to no. Its occurrence in second-order peak can be illustrated by integrating Eq. (9) with respect to time from zero to infinity;
∫0∞Itdt=−∫nondn=no−n∞=noE14
Both in the first order and second order, as well as other cases, n∞ is zero and therefore the integral, which represents the area under the glow peak is equal (in appropriate units) to no.
Now we can consider the dependence of different portions of the second-order peak on no. First, we shall study the dependence of I on no for a given temperature T. In the initial rise range, Eq. (12) reduces to:
IT≅no2S′exp−EKTE15
This shows immediately that for a given temperature in this range the dependence of I on no is superlinear, namely I α no. It is to be emphasized that it is true only in the initial rise region; as already shown the total area is proportional to no and different dependencies are expected on other portions of the curve. Using the maximum condition equation and approximation to ∫Texp−E/KTdT, it can be shown that the two terms in the brackets in Eq. (12), namely unity and noS′βToexp−E/KTdT are more or less equal at T = Tm. At higher temperature, the latter term increases substantially and the unity can be neglected so that we obtain:
I≅S′no2exp−EKTS′βno∫Texp−EKTdT−2
yields→I≅S′exp−EKTS′β∫Texp−EKTdT−2E16
The main point in Eq. (18) is that the term includes no cancel. This means that at a higher temperature range the TL intensity is independent of no for any given temperature [17].
Figure 5 shows plotted glow peaks using Eq. (12) for different no. In the low-temperature range, the TL intensity appears to depend on no. As no increases, Tm decreases which makes the peaks appear to be shifted to the low-temperature side. As the temperature increases the effect of no on the peak starts to decrease which makes the peaks approach each other’s on the high-temperature side.
Figure 5.
Plotted glow peaks using the second-order kinetics equation for different no.
3.1.2 A single TL peak analysis
As seen in Figure 6, the concentration of the trapping state is denoted by N (m−3), with n(t) (m−3) being filled by electrons at time t(s). These electrons can be thermally elevated into the conduction band by crossing an energy barrier of E (eV) at a rate proportional to exp.(−E/kT), resulting in a concentration of free electrons nc(t) (m−3). Following that, these can be retrapped in a similar trap with a re-trapping probability An or recombined with a trapped hole in a center with a recombination center probability Am, generating a photon with the recombination center energy h. A set of three simultaneous differential equations governs this operation. The following factors influence the recombination process:
Iαncmyields→I=−dmdt=AmncmE17
where n, m, and nc are the trapped electron, hole in the center, and free-electron concentrations, respectively, and (dm/dt) is the recombination rate. This means that the amount of light emitted is proportional to the pace at which m decreases. The rate of recombination is proportional to both the instantaneous concentration of free electrons nc and the concentration of hole centers m, the proportional constant Am (m3 s−1). The product of cross-section recombination σ (m2) and thermal velocity is commonly used to calculate this value (m.s−1). The second equation is concerned with the movement of electrons that have been thermally liberated from the trapped condition. The rate of release of these electrons –dn/dt is proportional to the trapped electron concentration n (m−3) and the Boltzman constant exp.(−E/KT), with S serving as the proportional constant (s−1).
Figure 6.
A general treatment of the charge carriers’ transitions in the TL sample.
However, the actual rate of change of n is also related to the retraping term. The rate of retraping is proportional to the concentration of free electrons nc, and the unoccupied trapping states N-n, the proportional factor being the recombination probability An(m3s−1). Thus, the second combined equation is given by:
−dndt=Snexp−EKT−AnncN−nE18
The third equation is that of charge neutrality. In its simplest form, it should read m = n + nc. Taking the first derivative with respect to time, the charge neutrality condition can be written as:
dmdt=dndt+dncdtE19
yields→dncdt=Snexp−EKT−ncmAm+N−nAnE20
This equation has been given by Adirovitch [18] for phosphorescence and by Halperin and Braner [19].
Now let us discuss the kinetics of the process in more general terms and see how the simplified cases of first, second, and more general cases emerge from Eqs. (17)–(20). Two simplifying assumptions were first made by Adirovitch [18] and later by many other investigators [19, 20, 21, 22, 23]. These are related to the relation between the concentration of the electrons in the conduction band and in traps and to the rate of change of these concentrations, namely:
dddt≪dndt,nc≪nE21
Although, it seems to be the same connection between these two conditions, basically they are two separate relations and the occurrence of one does not necessarily imply the other. With these assumptions, Helperin and Braner [19] found the expression:
I=−dmdt=mAmmAm+AnN−nSnexp−EKTE22
Since this equation contains two unknown functions, n(t) and m(t), it cannot be solved without further assumption. As mentioned, Randall and Wilkins [14] wrote their first-order equation assuming strong recombination. This can be expressed in more specific terms. If we assume with relation to Eq. (22) that:
mAm≫N−nAn
The condition of Eq. (22) is the relation between functions rather than parameters. It is, therefore, possible that at the low-temperature range of a glow peak, the strong inequality holds, and at higher temperatures where m and n decreases, the inequality “weakens” may be inverted. This may result in a shift from first-order behavior to non-first-order behavior within the same peak [24].
Then we see that Eq. (23) takes the same form of Eq. (3). For linear heating rate function, the general solution of Eq. (23) is given by Eq. (24):
I=noSexp−EKTexp−Sβ∫Texp−EKTdTE24
Then from Eq. (22) with Randall and Wilkins [14] assumptions, we reached the first kinetics order equation.
The abovementioned second kinetics order, resulting from different assumptions associated with Eq. (22). In one set of assumptions, one can take n(t) = m(t) which is not very different from the parametric equality no = mo once the assumption nc≪n is made.
In addition, we have to assert the retraping dominates [15]
AnN−n≫mAmE25
We also suppose that the trap is far from being saturated, i.e., the retrapping duration.
Alternatively, one can assume, in addition to the concentration equality, that An = Am [18] which yields:
I=−dmdt=SNn2exp−EKTE31
Then Eq. (22) takes the same form of Eq. (8) which is found by Gralick and Gibson [15]. Where Eq. (30) sums up both these possibilities by employing the parameter S′ (m3s−1), the pre-exponential factor that replaces AmSAnN in one case and S/N in the other. The solution of Eq. (30) is given by Eq. (32)
I=S′no2exp−EKT1+S′βno∫Texp−EKTdT−2E32
It should be emphasized that two cases discussed so far, namely first and second kinetics order, are only special cases in a sense, extreme cases and the general case described by equations Eq. (17) through Eq. (19) may be neither first nor second order even if the simplifying conditions of Eq. (21) are assumed to be general. The resulting Eq. (20) consists of many intermediate cases that do not have a distinct kinetics order. Although, some researchers still attempt to determine for every TL peak a first or second kinetics order [25].
Several attempts [16, 26] have been made to add a third parameter to the two basic ones, the activation energy E and the pre-exponential constant S′ (or S), all the attempts extend the “order parameter” implied when talking about first or second-order peak. The order parameters considered so far as a discrete magnitude assuming the value of 1 and 2 can be extended to be a continuous parameter. It is to be noted, however, that the addition of a third parameter is in principle one step in the right direction since the general treatment should include eight parameters (E, S, Am, An, N, no, mo, nc). The best-known way of including the third parameter is that of general kinetics order, b, according to which one can assume that the glow peak is governed by [25].
I=−dndt=S′nbexp−EKTE33
The kinetics order, b, is normally considered to be between 1 and 2, but it can occasionally exceed this range [13]. The rationale behind writing Eq. (33) is as follows: it is readily seen that a first-order peak is asymmetric, where a second order peak is nearly symmetric. Following Halperin and Braner [19] and Chen [16] we can define the symmetry factor μg as:
μg=δωE34
where δ=T2−Tm,ω=T2−T1 as it is shown in Figure 7, and T1 and T2 are the low and high temperatures on half- maximum intensity, respectively. It has been shown [16] that for the first kinetics order, μg≅0.42 and the second kinetics order, μg≅0.52.
Figure 7.
Parameters used in the calculation of the symmetry factor.
Of course, intermediate symmetries represented by different values of μg are found and the simplest way to present them by taking 1<b<2 in Eq. (30). Chen [16] has shown that μg changes from 0.42 to 0.52 as b increasing from 1 to 2. The solution of Eq. (33) for linear heating rate β, is given by:
I=Snoexp−EKTb−1Sβ∫ToTexp−EKTdt+1−bb−1E35
where S=S′nob−1.Eq. (35) represents glow peak intensity according to the general kinetics order.
A few words of caution are in order with respect to this treatment. First, although Eq. (34) has been shown to quite accurately described measured TL peaks [27, 28], it is to be noted that in most cases it is only an empirical presentation and is not based on the three differential equations [Eqs. (17) up to (19)], seem to be more physically significant. However, the general order case is still important because it can handle intermediate circumstances and smooth the first and second-order cases as b1 and b2, respectively.
3.1.3 General-order kinetics
May and Partridge supposed the empirical equation that has been suggested to explain the thermoluminescence glow peak if the first or second-order kinetics do not describe the glow peak. The equation is namely the general- order kinetics and written by:
I=n0s′′exp−E/KT1+b−1s′′/β∫T0Texp−E/T′KdT′bb−1
Hence s′′=sNn0 is called the pre-exponential factor, b the order of kinetics and the rang supposed between 1 and 2 but sometimes this rang has able to be greater than those. The pre-exponential factor s′′ is constant for given the dose, however, it differs with changing the absorbed dose withn0.
3.1.4 Trap parameters evaluation techniques
3.1.4.1 Empirical methods
We can deduce that the higher the peak temperature Tm, the higher the activation energy Urbach [29], and Urbach [30] found empirically for KCl crystals:
EeV=TmK500E36
This can also be written as E = 23KTm and it differs according to the types of the sample. Halperin [19] deduced E = 38 KTm for NACL samples, and Miller and Bube [31] arrived at E = 39 KTm for LiF.
The maximum intensity of the peak, according to Randall and Wilkins [12, 13], occurs around the temperature where the electron escape probability is 1 s-1. As a result of Eq. (1), we have:
P=Sexp−EKTm=1yields→E=KTmlnSE37
3.1.4.2 Initial rise method
According to Eqs. (6), (12) and (3), we can say that at the start of the glow peak (initial rise region) the TL intensity is proportional to exp−E/kT, irrespective of whether the first kinetics order is obeyed or not [32]. This temperature relationship persists until the quantity of trapped electrons is drastically reduced. Hence, by plotting Log (I) versus 1/T, the value of E can be obtained from the slope of the straight line obtained. As a result, using the equation: it is possible to calculate E without knowing the frequency factor S:
E=−KlnI1TE38
From Eq. (6), we see that when T is slightly greater than Tm, the argument of the second exponential is very small and therefore the value of the exponential function is close to unity and varies very slowly with temperature. The temperature dependence of I(t) is therefore dominated by the first exponential function, however the second exponential function decreases with increasing temperature and at higher temperatures it decreases very rapidly [13].
Therefore, the range of the initial rise must be chosen in which the second exponential function has minimum influence on the TL intensity temperature dependence. Therefore, it is necessary to restrict the temperature range such that the TL intensity does not exceed one-tenth of the maximum intensity [32].
Between temperatures T1 and T2 (both < Tm) corresponding to values equal to a1Im and a2Im respectively as in Figure 8, where:
Figure 8.
Extracted parameters from “Christodoulides expression” are to correct the value of the activation energy evaluated by the initial rise method.
a2≤0.5,a2a1≥5E39
On the temperature scale, a series of points were taken at equal intervals and plotted as ln(I) versus (1/T). The value Ec can then be calculated from the slope of the straight line as the energy determined by the initial rise technique; this value is smaller than the real activation energy E by the amount that grows as a1 and a2 increase. Christodoulides [33] devised the following expression for the corrected energy E in terms of the measured values Ec, a1, and a2:
E=1+0.74a1+0.082a2Ec−2a1+0.22a2Tm11605E40
The range of applicability of this equation is restricted by:
10≪EKTm≪100E41
3.1.4.3 Peak shape method
Grossweiner [34] established the first peak shape approach for first-order peaks, writing:
E=1.41KTmT1τE42
Where: Tm is the temperature at the maximum intensity, T1 is the temperature at the half of the maximum intensity in low-temperature side, τ=Tm−T1 as in Figure 9. Grossweiner used the coefficient 1.51, which was later [20] amended to 1.41. Lushchik [35] developed a method for evaluating the activation energy by utilizing the high-temperature half width δ=T2−T1 for first peaks he suggested:
Figure 9.
Peak shape method used to calculate the activation energy.
E=KTm2δE43
and for second-order peak:
E=2KTm2δE44
Chen [16] improved these equations by adding a factor of 0.976 in front of the former and replacing the factor 2 by 1.71 in the latter.
Halperin and Braner [19] have derived their equations for both first [Eq. (45)] and second kinetics orders [Eq. (46)]:
E=1.51KTm2τ−3.16KTmE45
E=1.81KTm2τ−4KTmE46
Chen [16] managed to establish expressions for general kinetics order, which is dependent on the geometry factor of the glow peak which is defined by Eq. (35):
E=CφKTm2φ−bφ2KTmE47
Where φ stands for τ,δ,ω and the values of Cφ and bφ for the three methods are:
Cτ=3μg−0.42+1.51E48
Cδ=7.3μg−0.42+0.976E49
Cω=10.2μg−0.42+2.52E50
bτ=4.2μg−0.42+1.58E51
bω=1E52
bδ=0E53
whereμgis geometrical shape factor that equalδω.
3.1.4.4 Various heating rates method
As mentioned above about Eq. (7), Tm changes with the heating rateβ, writing Eq. (7) twice for heating rate β1 and β2 with maximum temperatures Tm1 and Tm2 we get [36]:
E=kTm1Tm2Tm2−Tm1lnβ1β2−lnTm12Tm22E54
The activation energy that will be evaluated from Eq. (54) will be of course in accord with the first kinetics order only. However, Chen and Winer [37], Chen and Kirsh [38] showed that it can be used as a very good approximation for nonfirst-order cases as well.
The maximum condition, Eq. (16), can also take the following form:
−lnβTm2=EK1Tm+lnESK
According to this equation, Hoogenstraaten [39] suggested using several heating rates, a plot of ln(β/T2m) vs. (1/Tm) should yield a straight line of slope E/K, so that the activation energy is evaluated. Extrapolation to 1/Tm → 0 gives the value of ln(E/SK) from which the frequency factor is immediately found. It was shown that a plot of ln(Im) versus 1/Tm for various heating rates usually yields a straight line too and the activation energy can be extracted similarly. It is to be noted from the theoretical point of view that β should be varied in as board a range as possible. However, this may cause various experimental difficulties. At very low heating rates, the maximum intensity will be low and in fact, the peak smeared, thus not allowing effective extraction of the experimental parameters. At high heating rates, a delay between the sample temperature and that of the measuring device impairs the temperature measurement. Moreover, temperature gradients within the sample usually occur at high heating rates which result in a smearing effect of a different kind. In practice, one should therefore compromise on a relatively narrow range of heating rates [10].
3.1.5 Three points method
A new technique was developed by Rasheedy [25], to evaluate the trap parameters from the measured glow curve according to the general kinetics order.
The behavior of a phosphor’s TL intensity is determined by the following equation, [40], for generic kinetics order.
I=−dndt=nbNb−1Sexp−EKTE55
Where I is the intensity of the TL, n (cm−3), is the electron concentration trapped at time t(s), N (cm−3) is the traps concentration and K (eV/oK) is the Boltzman constant. Eq. (55) is more general than the two equations describing the first and second kinetics orders.
Eq. (55) is a modification of Eq. (33) in which the pre-exponential factor is defined as: S′=SNb−1 instead of ′=Snob−1 .The solution of Eq. (55) is given by Rasheedy [40]:
I=noS"exp−EKT1+b−1S"β∫ToTexp−EKTdTbb−1E56
Where the pre-exponential factor S″ = S(no/N)b−1 which is constant for a given dose but it varies with changes in the absorbed dose, i.e., with n0.
This method is based on the proportional of the concentration of populated traps during the running of the TL to the area under the glow peak.
Ix is the TL intensity at temperature Tx at any portion of the glow peak as shown in Figure 10, then Eq. (55) becomes:
Figure 10.
Three points method used by Rasheedy [25] to investigate the equations used to calculate the trap parameters.
Ix=AxbNb−1Sexp−EKTxE57
Where Ax is the area under the glow peak between the temperatures Tx and Tf (the final temperature of glow peak). Similarly, we have:
Iy=Ixy=AybNb−1Sexp−EKTyE58
Iz=Ixz=AzbNb−1Sexp−EKTzE59
Where Iy and Iz are the TL intensities at temperatures Ty and Tz, respectively.
Then, the order of kinetics b can be obtained from Eq. (62). Once the order of kinetics b is determined, the activation energy E(eV) can be determined by using Eq. (60) or Eq. (61).
Since, at T=Tmyields→∂I∂T=0
From Eq. (56) and using Eq. (59) leads to the following expression [41]:
S"=βEexpEKTmbKTm2−b−1EexpEKTm∫ToTmexp−EKTdTE63
A simple analytical method has been developed to obtain the relative value of no in the case of general kinetics order [41]:
no=ImexpEKTmS´E64
where Tm, and Im can be obtained from the shape of the glow peak.
Thus, by calculating the kinetics order b, the activation energy E, and the initial trapped electrons number for many points that cover sufficient range on the glow peak, and taking the average value for each parameter, one can determine the trap parameters according to the general kinetics order.
3.1.6 Glow curve analysis (peak shape methods)
A review of the expression used in an intercomparison of glow curve analysis computer programs to evaluate TLD-100 glow curve is given in Ref. [42] where I(T) is written in the following form:
IT=ASexp−EKT1+Sb−1β∫ToTexp−EKTdtb1−bE65
where: A = area (counts); b = kinetics order; E = activation energy; I = intensity (counts per s, counts per K); S = frequency factor (s−1).
On the other hand, Eq. (66) is based on first order kinetics which was used by Puchalska, [43], to develop glow-curve analysis software, in the following form:-
where the constants a0, a1 … and b0, b1 … are listed in the followings: -
ao=0.26777bo=3.9584
a1=8.63476b1=21.099653
a2=18.05901b2=25.63295
a3=8.573328b3=9.573322
Equation (68) will be used throughout our results which give better fitting to the resultant deconvoluted peaks. Different software was developed by Ratovonjanahary et al. [32], which uses the first kinetics order with an approximation of the second kinetics order. In this software the following equation was used:
IT=Imexp1+EKTT−TmTm−T2Tm2expEKT−T−TmTm1−∆−∆mE68
where,
∆=2KTE,∆m=2KTmE
Such a technique was also developed to analyze the glow curve using Eq. (53) by Rasheedy [41], which used the value of the trap parameters obtained by the three points method.
4. Modern clinical applications of TLD
TLD is widely used in various clinical fields for different purposes. The key reasons are undoubtedly their widespread availability, well-studied dosimetric characteristics, and applicability across a broad dose range. Imaging and Radiation Oncology Core-Houston IROC-H conducts remote dosimetry audits on MV photon and electron beams. IROC-H usually used integration between TLD-100 and other dosimetry system like nanoDot or diode systems for achieving the dose commissioning and calibrating dosimetry systems in an acrylic mini-phantom [44]. The failure rate was recorded in dose curves after modeling of the TPS (RayStation-Elekta Inc.) using phantom tests, which was not observed by patient-specific IMRT QA. Such failure was related to little changes in the MLC leaf-tip offset rather than leaf-tip width. Koger and his team [45] in IROC-H prosed four labeled TLD distributed in an anthropomorphic head-and-neck phantom for correcting such failure, (see Figure 11). It was utilized a 3D diode array were used in addition to assess the detectability of modeling mistakes [45].
Figure 11.
TLDs were labeled in head-and-neck phantom at IROC-H [45].
Another crucial issue is to increase the staff’s awareness about radiation safety and enhance radiation protection against unnecessary radiation doses. For such purpose, TLD-100 was recently used to validate occupational doses both inside and outside the nuclear medicine department, radiation protection purposes as well as the dose rate distribution around the positron emission tomography or computed tomography (PET/CT) [46].
Some recent studies were envisaged to see how the department compared to reports from other centers across the world in terms of the annual number of procedures and exposure limits, and to see if there was an opportunity for further radiation protection enhancements. As an example, personal TLD was calibrated to estimate the personal equivalent dose Hp (10) and Hp (0.07) at PET/CT. It was used for assessing the employee’s exposure [47]. On the other hand, TLD rings personal dosimeters were worn by surgeons in their fingers through sentinel node biopsy procedure to measure personal doses Hp(10) and Hp(0.07), as well as ambiental dose for operating theater and during injection [48]. This will assure that personal equivalent doses are within the acceptable annual determined limits [49].
Other important recent TLD application in diagnostics is using an anthropomorphic phantom that modeled the reference person to get a conversion coefficient connecting dose area product (DAP) to effective patient dosage. They concluded that the effective dosage at the clinical dark-field radiography system, which generates both attenuation and dark-field pictures, is within the range of chest radiography standard dose values [50].
TLDs showed to be an excellent choice for skin dosimetry. Omojola et al. [51] used TLD in measurements of 3D skin dosimetry and verify their results using TPS planning verification at specific spots in the phantom. A full perspective of the dose distribution was achieved; however, they revealed that regions outside the PTV require special attention [52, 53, 54].
In addition, in the field of proton therapy, a novel tissue-equivalent TLD-sheet of manganese doped lithium triborate showed a valuable and effective dosimetry technique. It may also be a great in vivo skin dosimetry instrument for proton treatment due to its flexible and reusable properties. Despite the presence of significant energy dependences in the Bragg peak region, the response properties studied in this work, including as reproducibility, fading effects, dosage linearity and dose homogeneity are acceptable [55].
Monte Carlo (MC) simulation is considered a good tool to understand well the TLD [56]. Some algorithm methods based on MC as if pencil beam could be involved in accurate dose in MV radiotherapy calculations. It could be useful to calculate the spectrum inside the detector based on four categories primary photon and electrons and secondary photon and electrons [57].
On the other hand, Low-energy (100 keV) photons (x-rays and gamma) have been widely employed in biological research and medical applications for more than a century, including mammography, fluoroscopy, general radiography, computed tomography, and brachytherapy treatment, among others. The majority of electrons created by low photon energy beams have energies below 10 keV, according to research. The physical processes through which these low-energy electrons interact with matter, on the other hand, are still unknown. Furthermore, it is commonly thought that all energy put within a dosimeter-sensitive volume is converted into a response. However, this assumption could be inaccurate because some of the deposited energy could be utilized to build flaws or damages at the molecular and atomic levels [58].
The hybrid-functional density theory (H-DFT) has shown to be a promising tool for localizing secondary electrons within a dosimeter volume and calculating the energy spent on creating defects or colors centers, among other things, when it comes to the relationship between the energy deposited and the response of a dosimeter. Following that, the quantity of energy that can be truly turned into a dosimeter response following exposure to ionizing radiation would be more accurately determined.
5. Conclusion
The aim of this chapter is concerned with TLD materials, measurements and recent various applications in clinical and industrial fields. TL kinetics are also covered in details due to their importance in knowing traps parameters and band structure-related phenomena that are responsible for TL phenomena. Modern clinical applications of TLD are also covered like quality assurance purposes for proton, x-ray and gamma radiotherapy based on phantom tests. In addition, we shed spot on using TLD for recent accurate methods for skin dose evaluation under IMRT/VMAT radiotherapy. Special attention should be oriented to hybrid-functional density theory Monte Carlo simulation to model TL dosimeters. Recent studies proved a promising tool for localizing secondary electrons within a dosimeter volume and calculating the energy spent on creating defects or colors centers, among other things, when it comes to the relationship between the energy deposited and the response of a dosimeter. Such methods could give knowledge about misunderstanding behaviors of some TLD and could eliminate its disadvantages like missing TL signal or fading; angle and energy of incidence ionizing radiation. In general, the properties of TLD like its inexpensive cost and reusability; easily fabricated, lightweight to wear, readout is simple and can be automated, insensitive to humidity make it advantageous in different clinical and radiation safety applications.
\n',keywords:"TLD, TL kinetics, radiotherapy, hybrid-functional density theory, modern clinical applications",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80975.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80975.xml",downloadPdfUrl:"/chapter/pdf-download/80975",previewPdfUrl:"/chapter/pdf-preview/80975",totalDownloads:42,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 29th 2021",dateReviewed:"January 17th 2022",datePrePublished:"March 25th 2022",datePublished:null,dateFinished:"March 25th 2022",readingETA:"0",abstract:"Due to the risk of radiation exposure, radiation dosimetry is performed regularly to ensure the occupational safety of personnel and radiation workers. Therefore, various dosimeters are widely used to detect neutrons, gamma, X-ray, and proton irradiation fields. As an example, in medical applications, routine personal dosimetry is used to monitor and limit workers’ long-term occupational exposure. Radiation workers who undertake X-ray diagnostic, radiotherapy operations, in clinical and industrial application. Although, the overheads of running an in-house TLD (Thermoluminescent dosimetry) service for monitoring doses to eyes, pacemakers and so on seems rather high for the benefits conferred, however, it is still widely used for reporting doses accurately in various medical centers over the world. TLD also is widely used for measuring entrance doses on a handful of patients to validate a new LINAC/TPS combination. As well as in the industrial field as if petroleum, companies or nuclear reactor, RSO (radiation safety officer) used TLD badges to report delivered doses. In this chapter, we focus on the TLD technique for measuring doses of various ionizing radiation detection. Different methods for evaluations of TL Kinetics are covered. Modern TLD applications in the clinical field are also investigated. Some recommendations on advance dosimetry failure of TLD are concluded.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80975",risUrl:"/chapter/ris/80975",signatures:"Hossam Donya",book:{id:"11247",type:"book",title:"Dosimetry",subtitle:null,fullTitle:"Dosimetry",slug:null,publishedDate:null,bookSignature:"Dr. Thomas J. FitzGerald",coverURL:"https://cdn.intechopen.com/books/images_new/11247.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-460-0",printIsbn:"978-1-80355-459-4",pdfIsbn:"978-1-80355-461-7",isAvailableForWebshopOrdering:!0,editors:[{id:"241806",title:"Dr.",name:"Thomas J.",middleName:null,surname:"FitzGerald",slug:"thomas-j.-fitzgerald",fullName:"Thomas J. FitzGerald"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"297802",title:"Dr.",name:"Hossam",middleName:null,surname:"Donya",fullName:"Hossam Donya",slug:"hossam-donya",email:"hdunia@kau.edu.sa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297802/images/17391_n.jpg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 TLD applications in neutron and gamma ray dosimetry",level:"2"},{id:"sec_1_3",title:"1.1.1 Albedo neutron dosimeter",level:"3"},{id:"sec_2_3",title:"1.1.2 Hydrogenous radiator TLDs",level:"3"},{id:"sec_3_3",title:"1.1.3 LET-dependent deep trap TLD glow peaks",level:"3"},{id:"sec_6",title:"2. Characteristic of TLD phosphors",level:"1"},{id:"sec_6_2",title:"2.1 The glow curve",level:"2"},{id:"sec_7_2",title:"2.2 TL sensitivity",level:"2"},{id:"sec_8_2",title:"2.3 Dose rate dependence",level:"2"},{id:"sec_9_2",title:"2.4 Stability",level:"2"},{id:"sec_11",title:"3. TL kinetics",level:"1"},{id:"sec_11_2",title:"3.1 First kinetics order",level:"2"},{id:"sec_11_3",title:"3.1.1 Second kinetics order",level:"3"},{id:"sec_12_3",title:"3.1.2 A single TL peak analysis",level:"3"},{id:"sec_13_3",title:"3.1.3 General-order kinetics",level:"3"},{id:"sec_14_3",title:"3.1.4 Trap parameters evaluation techniques",level:"3"},{id:"sec_14_4",title:"3.1.4.1 Empirical methods",level:"4"},{id:"sec_15_4",title:"3.1.4.2 Initial rise method",level:"4"},{id:"sec_16_4",title:"3.1.4.3 Peak shape method",level:"4"},{id:"sec_17_4",title:"3.1.4.4 Various heating rates method",level:"4"},{id:"sec_19_3",title:"3.1.5 Three points method",level:"3"},{id:"sec_20_3",title:"3.1.6 Glow curve analysis (peak shape methods)",level:"3"},{id:"sec_23",title:"4. Modern clinical applications of TLD",level:"1"},{id:"sec_24",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Furuta Y, Tanaka S. Response of 6LiF and 7LiF thermoluminescence dosimeters to fast neutrons. 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Impact of the MLC leaf-tip model in a commercial TPS: Dose calculation limitations and IROC-H phantom failures. Journal of Applied Clinical Medical Physics. 2020;21(2):82-88'},{id:"B46",body:'Nilsson I, Himmelman J, Khan J, Dalmo J. The potential to use Tld measurements to validate the occupational radiation protection at the Department of Nuclear Medicine. Radiation Protection Dosimetry. 2021;195(3-4):355-362'},{id:"B47",body:'Pavičar B, Davidović J, Petrović B, Vuleta G, Trivić S, Šajinović V, et al. Nuclear medicine staff exposure to ionising radiation in 18F-FDG PET/CT practice: A preliminary retrospective study. Arhiv za Higijenu Rada i Toksikologiju. 2021;72(3):216-223'},{id:"B48",body:'Petrovic B, Vicko F, Radovanovic D, Samac J, Tot A, Radovanovic Z, et al. Occupational radiation dose of personnel involved in sentinel node biopsy procedure. Journal of Medical Physics. 2021;91:117-120'},{id:"B49",body:'Ali W, Sulieman A, Tamam N, Boshara N, Aldhebaib A, Alkhorayef M, et al. 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Angular dependence of optical fibre thermoluminescent dosimeters irradiated using kilo- and megavoltage X-rays. Radiation Physics and Chemistry. 2017;135:4-10'},{id:"B54",body:'Moradi F, Mahdiraji GA, Dermosesian E, Khandaker MU, Ung NM, Mahamd Adikan FR, et al. Influence of dose history on thermoluminescence response of Ge-doped silica optical fibre dosimeters. Radiation Physics and Chemistry. 2017;134:62-70'},{id:"B55",body:'Kato T, Sagara T, Komori S, Kato R, Takeuchi A, Narita Y. Dosimetric properties of a newly developed thermoluminescent sheet-type dosimeter for clinical proton beams. Journal of Applied Clinical Medical Physics. 2021;22(4):158-165'},{id:"B56",body:'Donya H, Seniwal B, Darwesh R, Fonseca TC. Prospective Monte Carlo simulation for choosing high efficient detectors for small-field dosimetry. In: Theory, Application, and Implementation of Monte Carlo Method in Science and Technology. London: IntechOpen; 2019'},{id:"B57",body:'Donya H. Pencil-beam fluence evaluation based on Monte Carlo simulations algorithm of high energetic treatment photons. Journal of Medical Signals and Sensors. 2018;8(2):81'},{id:"B58",body:'Massillon-JL G. Future directions on low-energy radiation dosimetry. Scientific Reports. 2021;11:10569. DOI: 10.1038/s41598-021-90152-3'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Hossam Donya",address:"hdunia@kau.edu.sa",affiliation:'
Faculty of Science, Department of Physics, King Abdulaziz University, Saudi Arabia
Faculty of Science, Physics Department, Menoufia University, Egypt
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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. 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