**1. Introduction**

Bioanthropological1 researches carried out in the last few decades have given special emphasis to the study of the relation between disease, as well as social and environmental phenomena, enhancing the already strong connection between lifestyle and health conditions during history of humankind (Cohen & Armelagos, 1984; Katzenberg & Saunders, 2008; Larsen, 1997). Because infectious diseases result from the interaction between host and agent, modulated by ecological and cultural environments, the comparative study of the historic prevalence of diseases in past populations worldwide can provide important data about their related factors and etiology.

The study of dental diseases (such as caries) has been given special attention from Paleopathology2. The tooth, for its physical features tends to resist destruction and taphonomic conditions better than any other body tissue and therefore, is a valuable element for the study on individual's diet, and social and cultural factors related to it, from a population perspective.

Caries is one of the infectious diseases more easily observable in human remains retrieved from archaeological excavations. For their long time of development and non-lethal nature the lesions presented at the time of the death remain recognizable indefinitely, allowing to infer, along with other archaeological and ecological data, the types of food that a specific population consumed, the cooking technology they used, the relative frequency of consumption, and the way the food was shared among the group (Hillson, 2001 2008; Larsen, 1997; Rodríguez, 2003).

1 Formerly called Physical Anthropology, Bioanthropology is a discipline that provides integrated information about the lifestyle of past populations and their associations with the environment through the study of human remains. The North American school denominates it Bioarchaeology (Buikstra & Beck, 2006; Larsen, 1997; Roberts & Manchester, 2005).

2 In general, diseases, signs and determining factors have been studied by Bioanthropology under the label of Paleopathology (the study of diseases in past societies through ancient texts, art and human remains). The specific study of the oral diseases during ancient times is named Oral or Dental paleopathology (Campillo, 2001; Waldron, 2009).

Caries Through Time: An Anthropological Overview 5

diet entirely based on raw meat and vegetables, the patterns of chewing, digestion and nutrition changed accordingly. The process of cooking using fire turned the food safer, juicer, and easier to digest, promoting a higher intake of energy that, in evolutionary terms, had a sequence of favorable physiological effects. The easy digestion of cooked food would have favored the reduction of the digestive system, facilitating metabolic energy savings that were used to develop the brain (Aiello & Wheeler, 1995; Cartmill, 1993; Wrangham, 2009). Nevertheless, it is supposed that *H. erectus,* a hunter-gatherer, obtained approximately 50% of its calories from carbohydrates (Wrangham, 2009) and under the hypothesis of cooking (that obviously included meat and vegetables), caries should have been present much earlier in the fossil record. However, caries appears clearly much later. So, the data on oral does not support the idea of a cariogenic diet based on cooked vegetables from the earliest periods. Maybe, in

The unquestionable oldest evidence of caries comes from a fossil found in 1921 in Broken Hill, Northern Rhodesia (Zambia) during the exploration of a zinc mine. The specimen denominated Broken Hill 1, a *Homo rhodesiensis* cranium (African version of the *Homo heidelberguensis*  650,000-160,000 BP) shows extensive dental caries and coronal destruction. Except for five teeth, all the rest is affected by rampant caries and several crowns are almost completely destroyed. Caries seems to have its origin in the interdental spaces. Besides, Broken Hill man experienced alveolar recession and dental abscesses in many teeth (Fig. 1). Although lesions have been attributed to a diet rich in vegetables and/or poisoning by the existing metals in the region (Bartsiokas & Day, 1993), it seems that, given the interdental origin of the caries and the absence of tooth picks evidence, the Broken Hill 1 developed his lesions due to his ignorance in

Fig. 1. **The unquestionable oldest evidence of caries in the human paleontological record.**

Pictures of *H. rhodesiensis* skull cast. Map modified from Google Maps 2010.

the use of tooth picks, which was known by other earlier hominines (Puech, 1978).

the beginning, fire was employed only for cooking meat.

Considering the available data, we know that the highest caries rates3, their distribution and severity profiles observed nowadays are the result of a complex process of slow dietary changes, directly linked to the development of Western civilization. Consequently, the current caries patterns are not observed in past populations, on the opposite, they show a high variability along time and space that corresponds to a wide range of subsistence strategies, specific cultural regulations, and particular historical processes.


*2.2. Carbon Nanotubes*

Carbon nanotubes (CNTs) are a kind of carbon nanomaterial with unique electrical transmission properties and a large specific surface area, with excellent chemical, mechanical, and thermal stability, and direct binding with other molecules. Therefore, they have received great attention in biosensor design [37,38]. They can be thought of as cylindrical tubes made of one or more sheets of graphene rolled and folded. Nanotubes formed from a single sheet of graphene are called single-walled nanotubes (SWNT), with diameters between 0.4~2 nm, and multi-walled carbon nanotubes(MWCNTs) are 2~10 times larger [39]. Graphene contains SP2 hybrid carbon atoms, and nucleic acids can easily be attached to the surface of the nanotubes through π-π bonds, so CNTs are often used to carry ssDNA or RNA. In 2005, So et al. [40] constructed a biosensor using single-walled CNTs by using aptamer as a molecular recognition element for the first time. Since then, the potential of CNTs in sensing platforms has been gradually explored.

It is more common to modify electrodes with MWCNTs and then fix aptamers on the surface of MWCNTs. Zhu et al. [41] used carboxylic acid group functionalized MWCNTs to fix aptamers. Because the material has a large surface area and good charge transferability, the DNA attachment amount and sensor performance could be significantly improved. The sensor could detect Pb2+ in the range of 5.0 × 10−11~1.0 × 10−14 M. Additionally, Zou et al. [42] covalently immobilized aptamers on carboxylic functionalized MWCNTs by EDC/NHS chemistry. CNTs can not only carry aptamers in sensors but also provide binding sites for the reactions between aptamers and other nanomaterials. Rabai et al. [43] modified the electrode surface with CNTs, then deposited AuNPs on the composite electrode. Finally, with the aptamer fixed, the sensor had a detection limit of 0.02 pM for Cd2+. He et al. [44] developed an electrochemical sensor with a Zn3(PO4)2 modified aptamer and found that the sensor with MWCNTs had higher sensitivity.

#### *2.3. Graphene*

Graphene is a two-dimensional carbon nanomaterial with SP2 hybrid connected carbon atoms tightly packed into a single layer honeycomb lattice structure. Due to its excellent electrical properties, graphene has attracted great interest in recent years. Graphene has a unique type of structure that also gives it features not found in many other nanomaterials; its large specific surface area makes it an ideal candidate for immobilizing large numbers of functionalized metal oxides and noble metal nanoparticles [45]. Exceptional carrier mobility offers great prospects for nanoscale applications, such as electronic devices and chemical/biological sensors. In addition, its high electron transfer efficiency and wide electrochemical window make graphene an ideal material for constructing a highly sensitive E-apt sensor [46]. In recent years, graphene as a REDOX molecule in electrochemical sensors has attracted great attention.

The most common use of graphene in sensors is to modify electrodes. Zhang et al. [47] developed an Hg2+ detector for a graphene-fixed aptamer probe with a detection limit of 5 pM. Using graphene-modified electrodes, the modified electrode surface can be reused. Similar to AuNPs, it is more likely that graphene will be coupled with other nanomaterials to form new composite materials for better modification. Hai et al. [48] modified the electrode with AuNPs coupled with graphene. The aptamer was self-assembled on the electrode, and the detection limit of Pb2+ was as low as 3.8 pM. Jiang et al. [49] designed a new nanometer composite material consisting of TiO2, AuNPs, and nitrogen-doped graphene. The composite exhibits excellent optical properties, increasing the exciton lifetime and improving the charge transfer photocurrent intensity to 18.2 times higher than that of original TiO2. Wang et al. [50] synthesized another new material modified electrode by using CS instead of AuNPs for the detection of Pb2+. The modified electrode showed good repeatability, stability, and specificity to other interfering metal ions. Li et al. [51] prepared a sensor for mercury ions based on a perylene-3, 4, 9, 10-tetracarboxylic acid/graphene oxide (PTCA/GO) and quercetin-copper(II) complex. They efficiently promoted the separation of photoexcited carriers and enhanced the photocurrent.

#### *2.4. Quantum Dots*

Quantum dots (QDs), also known as semiconductor nanocrystals, are mixtures of cadmium and selenium or tellurium with nanoscale clusters with diameters of 1–20 nm [52]. Due to their unique properties, such as high quantum yield, excitation-dependent emission, surface modification versatility, and long-term photostability [53,54], QDs have been used in many research fields, especially in nanoelectronics, optoelectronics, and biological analysis [55]. The physical size of the nanocrystals determines the wavelength of the emitted fluorescence, so multiple analyses can be performed using a single excitation source. With the rapid development of nanotechnology, such nanomaterials have been widely used to improve the sensitivity of sensors. When they are incorporated into the design of biosensors, they can be used as tags, as part of a signal sensor [56].

QDs are mainly used in electrochemical luminescence sensors and photoelectric electrochemistry sensors. When the aptamer reacts with the corresponding target, the brightness of the QDs will also change due to the resonance energy transfer, thus improving the sensitivity of the sensor. CdTe QDs are most frequently used in sensors; Shi et al. [57]

developed a new method for the detection of Pb2+ based on the sensitization effect of CdTe QDs. When the target is present, the labeled QDs close to the electrode surface produce a sensitization effect and the photocurrent intensity is enhanced. Feng et al. [58] modified CdTe QDs with MIL-53 and determined Hg2+ and Pb2+ simultaneously by the ECL method with good recovery. Except for CdTe QDs, there are many other types of QDs, such as CdS and nitrogen-doped graphene (NG) [59,60], and their principle of action is roughly the same. When the conformation of the aptamer changes, the distance between the QDs and the electrode alters, and the electrical signal is either enhanced or weakened. This property makes QDs widely used to design E-apt sensors for food and water analysis.


**2.5 Synthesis to create a detailed solution**

On the basis of analysis of the individual solution component, all design is focused to furnish comprehensive alternative solutions. In this phase of design, calculations, specifications, performance predictions, cost estimates, scheduling procedures and the experimentation are involved.

further refining the result or design that has been recommended for action. The main objective of the design is to ensure that a desire goal and quality will achieved

After implementation of the design, its performance is monitored and recorded. Remedial measurements are suggested for more improvement of the performance

There are different significant design techniques in rock engineering. They are classified into three groups which are Analytical, Empirical and Observational. Rock masses having more complex in nature. Due to the very complex nature of rock masses and the difficulties encountered with their characterization, the analytical approach is the least used in the present engineering practice. Due to this reason, it does not lie in the analytical techniques themselves, since some have been developed to a high degree of sophistication, but in the inability to furnish the necessary input data as the ground conditions are adequately explored. Consequently, such analytical techniques as the finite element method, the boundary element method, closed form mathematical solutions, photo-elasticity or analogue simulation are mainly useful for assessing the influence of the various parameters or processes and for comparing alternative design schemes; they are the methods of the future not as yet acceptable as the practical engineering means for the design of rock tunnels [5]. Empirical methods of design are commonly applied as these are built on earlier practices derived from creation of rock structures owning alike physical characteristics [6]. It is a good practice to evaluate the stability of tunnels using at least two Empirical methods and validate through Numerical methods. Therefore, these two

The empirical approach relates the experience encountered at previous projects to the conditions anticipated at a proposed site. If an empirical design is backed by a systematic approach to ground classification, it can effectively utilize the valuable practical experience gained at many projects, which is so helpful to exercising one's engineering judgment. This is particularly important since, a good engineering design is a balanced design in which all the factors which interact, even those which cannot be quantified, are taken into account; the responsibility of the design engineers is not to compute accurately but to judge soundly. Rock mass classifications, which the main part of the empirical design methods, are extensively used tunnels within rock. At present, most of the tunnels excavated in the United States make use of some classification system. Terzaghi classification which was presented over 40 years ago is the most broadly used. In fact, rock mass classifications have been

The empirical methods of design may be used in association with other engineering assessment and design Techniques [6]. These methods are very essential and beneficial for the design in the earlier stages of the project, when minimum evidence about the behavior of rock mass, stress conditions and hydrological

within the time frame and the budget allocated.

*Design Techniques in Rock and Soil Engineering DOI: http://dx.doi.org/10.5772/intechopen.90195*

**3. Design techniques in soil and rock engineering**

groups of tunnel design methods will be discussed in detail [7].

**4. Empirical methods of design**

successfully applied throughout the world [5].

characteristics are obtainable [8].

**49**

**2.11 Feed back**

the solution design.

### **2.6 Evaluation of ideas and solutions**

In this phase the solution is interpreted and compare with the original hypothesis, specification, facts assumptions, requirements or constraints. This demand for a clear understanding of the all relevant interacting factors that's needed for the engineering judgments. The solution for engineering problems should be balanced involving all the factors with interact.

## **2.7 Optimization**

Optimization is the assortment of a best solution (with regard to some criteria) from some set of available alternative solutions [4]. There are always multiple solutions available to any engineering problem. Refinement and modification of a solution may then be required to reach a practicable agreement between the generally contradictory constraint and assets. The effectiveness of an optimization process mostly depends upon simplicity and clarity with which problem and solution are specified.

#### **2.8 Recommendation**

Recommendation is the principle of the whole Engineering design process. It provides a refined endorsement of the solution to problem, point out limitations and shows the trend to be followed in applying the solution.

#### **2.9 Communication**

The conclusive aim of the all design stages is the creation or instigation of a progression accomplishment. In order to achieve the objective requires the engineer must communicate the finding effectively. Effective communication means that all relevant aspects should be appropriately presented. If a mathematician were to sum up these thoughts, he might well do so by the Eq. (1).

$$E = \text{MC}^2 \tag{1}$$

Where,

E means effectiveness of the subject, M mean the mastery of the subject matter and C means the communication.

So for effective communication one should have sound knowledge of the subject matter and good communication skills. The design engineer must have the capability to communicate views and ideas concisely and clearly and to convey technical knowledge effectively.

#### **2.10 Implementation**

This is the final stage of design procedures. The finding or results communicated are applied under the given circumstance and proper monitoring is carried out for

further refining the result or design that has been recommended for action. The main objective of the design is to ensure that a desire goal and quality will achieved within the time frame and the budget allocated.


**7. Conclusion**

other cognitive functions, social interactions, behavior, and global quality of life (QOL). Interestingly, these differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from

Devinsky et al. later performed a double blind, placebo-controlled trial in patients with Dravet syndrome including 120 children and young adults using Epidiolex with a CBD dosage of 20 mg/kg/day. The median frequency of convulsive seizures per month decreased from 12.4 (baseline) to 5.9 with CBD, as compared with a decrease from 14.9 (baseline) to 14.1 with placebo (adjusted median difference between cannabidiol vs. placebo was −22.8% points [CI], −41.1 to −5.4; p = 0.01). The percentage of patients who had at least a 50% reduction in convulsive seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93–4.30; p = 0.08). This study shows an overall benefit of CBD over placebo but also

Another trial that assessed the efficacy of Epidiolex in reducing atonic seizures in patients with Lennox-Gastaut syndrome. In this double blind, placebo-controlled trial, a total of 225 patients were enrolled, 76 patients were assigned to a treatment group (20 mg/kg/day CBD) and 76 to the placebo group. The median percent reduction from baseline in monthly atonic seizure frequency during the treatment period was 41.9% in the treatment group vs. 21.8% in the placebo group. As with the other studies assessing Epidiolex, the most common adverse events among the patients in the treatment groups were somnolence, decreased appetite, and diarrhea [69]. A recent systematic review assessed the safety and efficacy of pharmaceutical grade CBD in pediatric onset drug resistant epilepsy with outcome measures including 50% seizure reduction, complete seizure freedom, improved QOL. A total of 36 studies were identified including 6 randomized controlled trials and 30 observational studies. Overall CBD at a dose of 20 mg/kg/day was more effective than placebo in reducing seizure frequency by 50% (Relative Risk 1.74: 1.24–2.43). For one patient to achieve a 50% reduction in seizures the number of patient needed to treat was 8. In pooled data of 17 of the observational studies CBD at 20 mg/ kg/day resulted in 48.5% of patients achieving a 50% reduction in seizures (95% CI: 39.0–58.1%) while pooled data from 14 observational studies showed 8.5% of patients became seizure free (95% CI: 3.8–14.5%). Quality of life improved in 55.8% of patients (95% CI: 40.5–70.6%) while serious adverse events related to treatment with CBD was very low at 2.2% of patients (95% CI: 0.0–7.9%). From this data, the authors concluded that pharmaceutical grade CBD may reduce seizure frequency but other randomized controlled trials examining a more diverse

group of epilepsy syndromes and other cannabinoids was needed [70].

To date, the evidence to support the use of cannabis in adults is minimal. STAR 1 is a phase 2A, randomized, double blind, placebo-controlled study that evaluated the safety and efficacy of synthetic transdermal CBD in adult patients with focal epilepsy. In this study 174 patients were randomized to receive either 195 mg CBD, 390 mg CBD or placebo via a transdermal patch. Patients who completed the 12-week study were able to continue into the 24-month open-label extension STAR 2 study (n = 171). In as of yet published data from these trials there was an increase in efficacy of transdermal CBD over 18 months. Median percentage change in seizure rates was −25% at 3 months, −40% at 6 months, −48% at 9 months, −52% at

its seizure reducing effects [67].

212 Recent Advances in Cannabinoid Research

a large placebo effect in the control group [68].

The cannabinoids found in cannabis appear to offer a unique pharmacological mode of action in the treatment of epilepsy. This, combined with the apparent low risk of serious side effects, makes cannabis and an attractive potential option for patients with treatment resistant epilepsy.

Currently, there is a large public perception that cannabis products are superior to and safer than conventional anti-epileptic medications especially in treating patients with Dravet syndrome and other pediatric onset epileptic encephalopathies. Based on interpretation of the available data, the authors feel that cannabis based therapies show promise in the treatment of children with treatment resistant epilepsies. While the studies to date assessing cannabis based therapies for the treatment of epilepsy have been encouraging, they should be interpreted with caution. At this time, the long-term adverse effects, the indicated epilepsy and seizure types suitable for treatment with cannabis, the dosing of CBD and other cannabinoids, remain unknown. Also, there is minimal data regarding the pharmacokinetics of the cannabinoids especially in children and when used in patients with multiple concomitant medications. Moreover, the existing studies are limited with the majority of them being retrospective and subject to bias, possible placebo effect, and other limitations.

As such, further studies assessing the safety and efficacy of cannabis based therapies in both adults and children are urgently needed. The authors recommend that these studies start with well-designed dose finding studies that include age stratified pharmacokinetic analysis followed by larger scale clinical trials. When faced with physicians that are reluctant to authorize cannabis based products due to a lack of high quality safety and efficacy data, parents who are desperate to help their children are then forced to turn to unregulated suppliers of cannabis. This puts their children at risk of harm and themselves in legal jeopardy.

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