Showing posts with label Lupine Publisher. Show all posts
Showing posts with label Lupine Publisher. Show all posts

Wednesday, 20 September 2023

Lupine Publishers | Treatment of Infected Primary Teeth using Modified Antibiotic Paste

 Lupine Publishers | Journal of Interventions in Pediatric Dentistry


Abstract

Objectives: Treatment of pulpectomized primary molars with chronic infection using a mixture of three antibiotics: Metronidazole, Ciprofloxacin, and Doxycycline mixed with Macrogol or Propylene Glycol (modified 3MIX-MP) as an intracanal medicament before the complete cleaning and shaping and obturation.

Study design: A 7 years old child with infected primary molar came to our clinic for treatment. A detailed medical history and drug allergy were taken. Ciprofloxacin (500mg), Metronidazole (500mg) and Doxycycline (100mg) tablets divided in the proportion of 1:3:3 (one part of Ciprofloxacin, three parts of Metronidazole, and three parts of Doxycycline) and mixed with propylene glycol to form an ointment. Biomechanical preparation was done. The modified 3MIX-MP paste placed in the pulp chamber then temporary filling. The patient was recalled after 2 weeks. The tooth was obturated and restored then a stainless-steel crown placed. Then reevaluated at 3rd, 6th, and 12th months.

Results: Excellent clinical and radiographic success when compared to conventional pulpectomy and non-instrumentational lesion sterilization tissue repair therapy.

Conclusion: Treatment of Primary molar with modified 3MIX-MP, followed by instrumentation and obturation provided excellent clinical and radiographic success when compared to non-instrumentational lesion sterilization tissue repair therapy.

Keywords: Pulp infection; Pulpectomy; Modified antibiotic paste; Primary molars; Chronic, infected pulp; Modified 3 MIX-MP; Pulpectomy; Triple antibiotic paste; Primary teeth

Introduction

The first topical antibiotic introduced to endodontics was Grossman’s polyantibiotic paste in 1951, later many topical antibiotics have been introduced with varying combinations, few of those include Septomixine forte; PBSC (Combination of Penicillin, Bacitracin, Streptomycin and Caprylate sodium), and Clindamycin. However, none of these combinations has proven to be 100% successful in eliminating all the bacterial strains from the root canal system [1-5].

Materials and Methods

A child aged 7 years old with chronic infection related to the lower left primary molar came to our clinic for treatment of the infected molar (Figure 1). Treatment was explained to the parents and written informed consent was taken from parents before start of the study. A detailed medical history and previous illness with a history of drug allergy were taken from the parents, then the mentioned primary molar was diagnosed clinically, the molar was badly decayed with signs of chronic infection such as: gingival swelling and tenderness to percussion. A radiographic examination was done and a per radicular radiolucency was found, with no excessive root resorption. Commercially available chemotherapeutic agents such as Ciprofloxacin (500mg) (Omacip, NPI Pharma, Oman), Metronidazole (500mg) (Anazol, JPI, Saudi Arabia), and Doxycycline (100mg) (Tabocine, TPMC, Tabuk) tablets were obtained [6,7], then these tablets were crushed into fine powder using sterile porcelain mortar and pestle. These powdered drugs were transferred into three separate sterile glass containers, capped tightly and stored in the refrigerator until its use. Just before use, each powdered drug was divided in the proportion of 1:3:3 (one part of Ciprofloxacin, three parts of Metronidazole, and three parts of Doxycycline) and were mixed with propylene glycol and polyethylene glycol to form an ointment. Reddy GA et al. Trairatvorakul and Detsomboonrat, Jaya et al., Cruz et al. also followed the similar protocol of preparation of 3MIX antibiotic paste [8-11].

Figure 1: Preoperative illustration.

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Figure 2: Postoperative illustration.

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Preoperative clinical and radiographical signs and symptoms were recorded. The tooth was anesthetized using 2% Xylocaine with 1:80,000 adrenalin and isolated with rubber dam. Access opening was performed using round bur, Biomechanical preparation was done using k files from size 10–25. The root canals were chemically cleaned with 1% sodium hypochlorite solution and dried with paper points. The 3MIX-MP paste placed in the pulp chamber and pressed with dampened cotton pellet and temporized with Cavit. The patient was recalled after 2 weeks for evaluation. The tooth was obturated with reinforced zinc oxide eugenol (IRM, Dentsply) using lentulo spirals. Then restored with glass ionomer restorative material (Riva self-cure, SDI) and reinforced by placing stainless steel crowns (Figure 2). Further, the treated tooth was reevaluated both clinically and radiographically at 3rd, 6th, and 12th months intervals postoperatively (Figure 3). At the time of revisits, the tooth was examined clinically for any signs of failure that includes a report of spontaneous pain, presence of swelling, sinus tract and mobility. Radiographic evaluation was done to check the radiolucency and signs of resorption. The tooth was asymptomatic without pain, swelling, sinus tract and mobility also there was no increase in furcation radiolucency or development of root resorption which is abnormal for the age of the child.

Figure 3: 12 months Follow up.

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Results

Excellent clinical and radiographic success when compared to conventional pulpectomy and non-instrumentational lesion sterilization tissue repair therapy.

Discussion

This study was approved by “Research Ethics Committee, Taibah University, College of Dentistry, TU CD-REC”. The concept of Non-Instrumentation Endodontic Therapy introduced by Niigata university school of dentistry; Japan has gained reputation as it proved to attain 100% sterility in the root canal system [12- 15]. They recommended a technique similar to pulpotomy where debriding only the pulp chamber of chronically infected primary teeth and placing medicament (ciprofloxacin, metronidazole, and minocycline) near the root orifice without preparing the radicular portion. Cruz et al. suggested vehicles such as macrogol and propylene glycol (3MIX–MP) and demonstrated that these vehicles will carry the medicament deep into the dentinal tubules, thus aid in effective eradication of bacteria [11]. Metronidazole (Nitroimidazole compound) due to its wide spectrum of antibacterial action against anaerobes (Ingham et al. 1975) gained importance as the 1st choice drug for triple antibiotic paste preparation [16,17]. Metronidazole binds to the DNA and disrupts its helical structure and thus leads to rapid cell death. However, metronidazole even at higher concentrations could not eradicate all the bacteria thus indicating the necessity of some additional drugs to sterilize these lesions [15]. The two other antibacterial drugs, i.e. ciprofloxacin, and minocycline, in addition to metronidazole (3MIX) were added in an effort to eliminate all bacteria [8,10,15,18]. The 2nd choice of drug ciprofloxacin is a synthetic fluoroquinolone with rapid bactericidal action. It inhibits the enzyme DNA gyrase of bacteria. It exhibits very potent activity against Gram-negative bacteria but very limited activity against Gram-positive bacteria. Most of the anaerobic bacteria are resistant to ciprofloxacin. Hence, it is often combined with metronidazole in treating mixed infections. The 3rd choice of drug was minocycline. It is a semisynthetic derivative of tetracycline, primarily bacteriostatic, inhibiting protein synthesis by binding to 30S ribosomes in susceptible organisms and exhibits broad spectrum of activity against Gram-positive and Gramnegative microorganisms [3].

In our present study we replaced Minocycline with Doxycycline due to the difficulty in obtaining Minocycline, and before using the Doxycycline as a replacement we have done further searches for previous studies to ensure that both medications have the same effect and this replacement will not affect the efficacy of the mentioned mix. The already done studies concerning the difference between both Doxycycline and Minocycline revealed that still no statistically significant differences had been demonstrated in clinical trials when comparing Minocycline with Doxycycline, and investigators had concluded that both are equally effective. And they differ in their adverse event profile [19]. Considerably fewer adverse effects have been reported for Doxycycline than Minocycline; the adverse effects for Minocycline are 5 times more common than for Doxycycline [19]. We have followed the same protocol of Reddy GA et al. of extirpation of both necrotic coronal as well as all accessible radicular pulp tissue and then complete obturation, which is reported successful clinically over 16th month follow-up [9]. Although the previous studies have demonstrated that the LSTR (Lesion Sterilization Tissue Repair) technique as one of the successful techniques for management of chronically infected primary teeth, the controversies aroused about the duration of therapeutic activity of the medicament and leaving the infected material in the radicular region. So that the present study planned where in treated tooth were revisited after 2 weeks for medicament removal and obturation.

Conclusion

All the primary teeth with chronic infection which were treated using modified 3MIX-MP, followed by the instrumentation and obturation provided excellent clinical and radiographic success when compared to conventional pulpectomy and noninstrumentational lesion sterilization tissue repair therapy.

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Tuesday, 22 February 2022

Lupine Publishers| The Role of Engineering Design in the Infection Control for Hospitals

 Lupine Publishers| Journal of Civil Engineering and its Architecture


Abstract

Hospital buildings are designed with intrinsic features for infection control, and are related to an intensive energy use. The infection control program is structured in a hierarchy of administrative, engineering and PPE controls. Building design plays a major role, because it must not only incorporate the systems that are responsible for infection's engineering controls, but also the features demanded by the administrative controls. Basic understanding of the infection control hierarchy and strategies and stringent communication with the HICC in the design phase is necessary, not only to provide a healthy and safe environment, but to achieve rational solutions that minimize the complexity, operational and maintenance costs. This review paper contributes with basic information about these topics, and presents references for detailed and advanced information.

Keywords: Infection control; Hospital; Healthcare; Engineering design; Ventilation

Abbrevations: ACH: Air Changes Per Hour; ASHRAE: American Society of Heating, Refrigerating and Air-Conditioning Engineers; CDC: Centers for Disease Control; DHHS: U.S. Department of Health and Human Services; HEPA: High Efficiency Particulate Air; HICC: Hospital's Infection Control Committee; HVAC: Heating, Ventilation and Air-Conditioning; MERV: Minimum Efficiency Reporting Value; PPE: Personal Protective Equipment; UVGI: Ultraviolet Germicidal Irradiation; WHO: World Health Organization

Introduction

Hospital buildings are designed with intrinsic features for infection control, which contribute to produce an intensive energy use and significant greenhouse gas emissions [1]. The scope of this review paper is to provide basic information on these intrinsic features, and relevant reference for advanced information.

The Infection control program

In order for an infection to occur, it is necessary the presence of the infectious agent and its source, the mode of transmission, and a susceptible host, in what is called the "infection chain" [2]. The bacterial agents are one of the most common pathogens related to hospital-acquired-infections (nosocomial infections) in the United States [3], but fungal and viral agents are also reported [3]. One of the main sources of these agents, in the hospital application, are the diseased patients. In this case, those pathogens use body fluid secretions, blood, feces and droplets expelled by the respiratory track, among others, as a portal of exit. The expelled droplets are produced in a broad range of sizes during the respiration, talking, coughing and sneezing processes [4]. The larger droplets (order ≥100 μm) settle down within a small distance from the source (1 to 2m), due to the gravitational action. The smaller ones (order < 100μm) may reach sizes that allow them to be suspended for a long time. References [5] and [6] provide detailed information about droplets dynamics in indoor environmental air.

The modes of transmission include direct contact during patient manipulation, indirect contact with contaminated surfaces (fomites) and airborne propagation (also a mode of indirect contact) [2]. Infection by the larger droplets is generally treated as direct contact [2]. Airborne propagation is related to droplet nuclei (size order ≤10μm) [7,8]. Reference [9] provides detailed information about airborne disease transmission.

The infection control program uses administrative, engineering and personal protective control measures [10], in the components of the "infection chain", in order to reduce the infection risk. Administrative controls are based on the stringent application of protocols. These require, among others, that universal precautions (hand hygiene, gloves when touching blood and secretions, etc.), must be used on all patient's manipulation, for instance. Surface disinfection and patient care products sterilization is another administrative control, among others. References [11] and [12] provide detailed information about the infection control program.

Engineering design and infection control

Building design must not only incorporate the systems that are responsible for infection's engineering controls, but also the features demanded by the administrative controls. The design team must keep in mind that engineering controls will not overcome the lacks in administrative controls, but these can promote protocols that can simplify the engineering design. Communication is a key factor for improving the engineering design.

Space design: Layout design must be planned in stringent relationship with the hospital’s infection control committee (HICC), geared to provide adequate patient, staff, materials and waste flows, in order to prevent cross contamination. Basic knowledge on droplet dynamics may be used to understand the infection control criteria that are used to size the gap between patient beds, geared to reduce the risk of cross infection by droplet direct contact. For the case of airborne transmission, the infection control program generally demands that patients with airborne communicable diseases (e.g. tuberculosis, measles, etc.) must be isolated in an airborne infection isolation room (AII) [11]. A Protective Environment room (PE) is generally demanded for the isolation of immunocompromised patients (e.g. bone marrow transplant, oncology, etc.) [11]. Basic knowledge on transmission modes may be used to understand the criteria that is used to request smooth and cleanable finishing for walls and floors, geared to meet the sanitization demands that reduce the risk of cross infection by indirect contact.

Ventilation for dilution control: Although dilution ventilation is a key factor in healthy indoor environments, the design team must be aware that the strategy of increasing ventilation rates, in mixing ventilation mode, has limited effectiveness on airborne infection control [13-16]. Moreover, using high ventilation rates, in air-conditioned spaces, increase energy consumption and may disturb humidity control in hot & humid climates, leading to undesirable mold growth and amplification [17]. Memarzadeh [9] provides an excellent literature review on the role of ventilation on airborne infection control. The reader shall address references [18] and [19] for design guidelines of HVAC systems for hospital applications. Examination of all these studies [13-16] and references [9,18,19] show that maximum rational ventilation rates for dilution control in mechanical ventilated spaces are in the order of 10 ACH. Administrative controls, like source isolation or elimination are more effective than the use of increased ventilation rates, for the prevention of airborne communicable diseases in the hospital setting. The isolation of a source patient in an AII room (single bed) is an example of an administrative control. Staff training for prompt triage of undiagnosed or unsuspected patients with symptoms suggestive of an airborne communicable disease in patient's waiting area is another example. Those patients may be asked to use a surgical mask and instructed to observe strict respiratory hygiene and cough etiquette procedures, while in general public area. Reference [20] provides additional information on administrative control measures for airborne communicable diseases. The WHO [21] provides a guide on natural ventilation for infection control in health-care settings, and this strategy may be an attractive solution for many design locations, notably the low- income developing countries. Reference [10] provides additional information on strategies for reducing healthcare building's energy use, while maintaining or improving effective airborne infection control.

Air filtering and disinfection: Guidelines demand the application of air filters in air-conditioned hospital settings [18,19]. These guidelines recommend that MERV-7 filters (efficiency > 90%, arrestance test) is the minimum filter requirement for coarse particulate control in any HVAC hospital application [18,22]. The requirement of additional filter banks, with higher efficiency for the fine mode particulate control, depends on the application, and is recommended for several ones, in the hospital setting [18,19]. ASHRAE recommends that MERV-15 filters shall be used in all area for inpatient care [18]. This recommendation needs to be analysed by the infection control point of view because of this filter’s high efficiency against the droplet nuclei size order and fine particles size order (size particle most likely to be deposited deep in the lung). Besides that, HEPA filters are often required for some applications, as AII and PE rooms, orthopedic and transplant surgery [18], among others. References [22] and [23] provide detailed information about air contaminants, particulate control and air filter ratings and testing. In the absence of local code requirements, references [18] and [19] provide guidelines on filter selection for air-conditioned hospital applications. However, the room particle concentration decay due to the filtering technique obeys the dilution equation. In this case, the precedent section discussion applies, about the limited efficiency of dilution on infection control. Moreover, the design team must be aware that the application of high-efficiency filters increases the energy use, due to enhanced fan power to overcome the higher pressure loss. In that case, refer to reference [24], for special design considerations that may reduce pressure drop, and provide a rational solution.

An attractive air disinfection technology for airborne infection control is the use of upper-room UVGI (ultraviolet germicidal irradiation) fixtures. This technique relies on the germicidal action of UV in the wavelength range of 200-270 nanometers [18]. The lamp fixture is designed to irradiate the upper-room (unoccupied) zone, while preventing direct irradiation of the occupied zone. An additional room air mixing system (natural or mechanical) is demanded to provide the transport of airborne particles from the occupied to the irradiation zone. References [25-28] provide studies and results on this technique, and references [29-31] provide detailed information on guidelines for installation.

Conclusion

Engineering design plays a major role in the infection control for hospitals. Besides providing the engineering controls, the hospital design must meet the requirements of administrative controls. Basic understanding of the infection control hierarchy and strategies and stringent communication with the HICC in the design phase is necessary, not only to provide a healthy and safe environment, but also to achieve rational solutions that minimize the complexity, operational and maintenance costs.

Read More About Lupine Publishers Journal of Civil Engineering and its Architecture Please Click on Below Link: https://lupinepublishers-civilengineering.blogspot.com



Monday, 29 March 2021

Lupine Publishers| Model Selection in Regression: Application to Tumours in Childhood

 Lupine Publishers| Current Trends on Biostatistics & Biometrics


Summary

We give a chronological review of the major model selection methods that have been proposed from circa 1960. These model selection procedures include Residual mean square error (MSE), coefficient of multiple determination (R2), adjusted coefficient of multiple determination (Adj R2), Estimate of Error Variance (S2), Stepwise methods, Mallow’s Cp, Akaike information criterion (AIC), Schwarz criterion (BIC). Some of these methods are applied to a problem of developing a model for predicting tumors in childhood using log-linear models. The theoretical review will discuss the problem of model selection in a general setting. The application will be applied to log-linear models in particular.

Keywords: MSE; R2; Adj R2; (S2); Stepwise methods; Cp; AIC; BIC

Introduction

Historical Development

The problem of model selection is at the core of progress in science. Over the decades, scientists have used various statistical tools to select among alternative models of data. A common challenge for the scientist is the selection of the best subset of predictor variables in terms of some specified criterion. Tobias Meyer (1750) established the two main methods, namely fitting linear estimation and Bayesian analysis by fitting models to observation. The 1900 to 1930’s saw a great development of regression and statistical ideas but were based on hand calculations. In 1951 Kullback and Leibler developed a measure of discrepancy from Information Theory, which forms the theoretical basis for criteria-based model selection. In the 1960’s computers enabled scientists to address the problem of model selection. Computer programmes were developed to compute all possible subsets for an example, Stepwise regression, Mallows Cp, AIC, TIC and BIC. During the 1970’s and 1980’s there was huge spate of proposals to deal with the model selection problem. Linhart and Zucchini (1986) provided a systematic development of frequentist criteria-based model selection methods for a variety of typical situations that arise in practice. These included the selection of univariate probability distributions, the regression setting, the analysis of variance and covariance, the analysis of contingency tables, and time series analysis. Bozdogan [1] gives an outstanding review to prove how AIC may be applied to compare models in a set of competing models and define a statistical model as a mathematical formulation that expresses the main features of the data in terms of probabilities. In the 1990’s Hastie and Tibsharini introduced generalized additive models. These models assume that the mean of the dependent variable depends on an additive predictor through a nonlinear link function. Generalized additive models permit the response probability distribution to be any member of the exponential family of distributions. They particularly suggested that, up to that date, model selection had largely been a theoretical exercise and those more practical examples were needed (see Hastie and Tibshirani, 1990).

Philosophical Perspective

The motivation for model selection is ultimately derived from the principle of parsimony [2]. Implicitly the principle of parsimony (or Occam’s Razor) has been the soul of model selection, to remove all that is unnecessary. To implement the parsimony principle, one has to quantify “parsimony” of a model relative to the available data. Parsimony lies between the evils of under over-fitting. Burnham and Anderson [3] define parsimony as “The concept that a model should be as simple as possible concerning the included variables, model structure, and number of parameters”. Parsimony is a desired characteristic of a model used for inference, and it is usually defined by a suitable trade-off between squared bias and variance of parameter estimators. According to Claeskens and Hjort [4], focused information criterion (FIC) is developed to select a set of variables which is best for a given focus. Foster and Stine [5] predict the onset of personal bankruptcy using least squares regression.

They use stepwise selection to find predictors of these from a mix of payment history, debt load, demographics, and their interactions by showing that three modifications turn stepwise regression into an effective methodology for predicting bankruptcy. Fresen provides an example to illustrate the inadequacy of AIC and BIC in choosing models for ordinal polychotomus regression. Initially, during the 60’s, 70’s and 80’s the problem of model selection was viewed as the choice of which variable to include in the data. However, nowadays model selection includes choosing the functional form of the predictor variables. For example, should one use a linear model, or a generalized additive model or even perhaps a kernel regression estimator to model the data? It should be noted that there is often no one best model, but that there may be various useful sets of variabsles (Cox and Snell, 1989). The purpose of this paper was to give a chronological review of some frequentist methods of model selection that have been proposed from circa 1960 and to apply these methods in a practical situation. This research is a response to Hastie and Tibsharani’s (1990) call for more examples.

Data and Assumptions

In this paper the procedures described here, will be applied to a data set collected at the Medical University of Southern Africa (Medunsa) in 2009. The data consist of all the tumours diagnosed in children and adolescents covering the period 2003 to 2008. The files of the Histopathology Department were reviewed and all the tumours occurring during the first two decades of a patient’s life were identified. The following variables were noted: age, sex, site. The binary response variable indicated the presence of either malignant (0) or benign (1) tumours. In our setting, the problem of model selection is not concerned with which number of predictor variables to include in the model but rather, which functional form should be used to model the probability of a malignant tumour as a function of age. For binary data it is usual to model the logit of a probability (the logit of the probability is the logarithm of the odds), rather than the probability itself. Our question was then to select a functional form for the logit on the bases of a model selection criterion such as Akaike information criterion (AIC) or Schwarz criterion (BIC).

We considered various estimators for the logit, namely using linear or quadratic predictors, or additive with 2, 3, and 4 degrees of freedom. As an alternation, the probabilities were modeled using Kernel estimator with Gaussian Kernel for various bandwidths, namely 8.0, 10.0 and 12.5. The model selection criterion that was used are AIC and BIC. Based on the above approach, recommendations will be made as to which criteria are most suitable for selecting model selection. The outline of this paper is as follows. In Section 2, we provide a brief review of the related literature. Section 3 presents technical details of some of the major model selection criteria. Some model selection methods which were applied to a data set will be discussed in Section 4. Finally, Section 5 will provide conclusions and recommendations.

Literature Review

The problem of determining the best subset of independent variables in regression has long been of interest to applied statisticians, and it continues to receive considerable attention in statistical literature [6-9]. The focus began with the linear model in the 1960`s, when the first wave of important developments occurred and computing was expensive and time consuming. There are several papers that can help us to understand the state-of-the-art in subset selection as it developed over the last few decades. Gorman and Toman [10] proposed a procedure based on a fractional factorial scheme in an effort to identify the better models with a moderate amount of computation and using Mallows as a criterion. Aitkin [11] discussed stepwise procedures for the addition or elimination of variables in multiple regression, which by that time were very commonly used. Akaike [12] adopted the Kullback-Leibler definition of information, as a measure of discrepancy, or asymmetrical distance, between a “true” model and a proposed model, indexed on parameter vector.

A popular alternative to AIC presented by Schwarz [13] that does incorporate sample size is BIC. Extending Akaike’s original work, Sugiura (1978) proposed AICc, a corrected version of AIC justified in the context of linear regression with normal errors. The development of AICc was motivated by the need to adjust for AIC’s propensity to favour high-dimensional models when the sample size is small relative to the maximum order of the models in the candidate class. The early work of Hocking [14] provides a detailed overview of the field until the mid-70’s. The literature, and Hocking’s review, focuses largely on (i) computational methods for finding best-fitting subsets, usually in the least – squares sense, (ii) mean squares errors of prediction (MSEP) and stopping rules. Thomson [15] also discussed three model selection criteria in the multiple regression set-up and established the Bayesian structure for the prediction problem of multiple regression.

Some of the reasons for using only a subset of the available predictor variables have been reviewed by Miller [16]. Miller [17] described the problem of subset selection as the abundance of advice on how to perform the mechanics of choosing a model, much of which is quite contradictory. Myung [18] described the problem of subset selection as choosing simplest models which fit the data. He emphasized that a model should be selected based on its generalizability, rather than its goodness of fit. According to Forster [9], standard methods of model selection, like classical hypothesis testing, maximum likelihood, Bayes method, Minimum description length, cross-validation and Akaike’s information criterion are able to compensate for the errors in the estimation of model parameters. Busemeyer and Yi-Min Wang [19] formalized a generalization criterion method for model comparison. Bozdogan [20] presented some recent developments on a new entropic or information complexity (ICOMP) criterion for model selection. Its rationale as a model selection criterion is that it combines a badness-of-fit term (such as minus twice the maximum log likelihood) with a measure of complexity of a model differently than AIC, or its variants, by taking into account the interdependencies of the parameter estimates as well as the dependencies of the model residuals. Browne [21] gives a review of cross-validation methods and the original application in multiple regression that was considered first. Kim and Cavanaugh [22] looked at modified versions of the AIC (the “corrected” AIC- and the “improved” AICM) and the KIC (the “corrected” KIC- and the “improved” KICM) in the nonlinear regression framework. Hafidi and Mkhadri derived a different version of the “corrected” KIC ÐKIC-) and compared it to the AIC- derived by Hurvich and Tsai. Abraham [23] looked at model selection methods in the linear mixed model for longitudinal data and concluded that AIC and BIC are more sensitive to increases in variability of the data as

opposed to the KIC

Frequentist Model Selection Criteria

Tools for Model Selection in Regression

Model selection criteria refer to a set of exploratory tools for improving regression models. Each model selection tool involves selecting a subset of possible predictor variables that still account well for the variation in the regression model’s observation variable. These tools are often helpful for problems in which one wants the simplest possible explanation for variation in the observation variable or wants to maximize the chance of obtaining good parameter values for regression model. In this section we shall describe several procedures that have been proposed for the criterion measure, which summarizes the model; These include coefficient of multiple determination (R2), Adjusted-R2 and residual mean square error (MSE), stepwise methods, Mallow’s Cp, Akaike information Criteria (AIC) and Schwarz criterion (BIC). The focus will be on AIC and BIC [24-28].

R2

Is the coefficient of multiple determination and the method to find subsets of independent variables that best predict a dependent variable by linear regression. The method always identifies the best model as the one with the largest for each number of variables considered.

This is defined as

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Where SSE (the sum of squares of residuals) and SSY

Adjusted R - square (adj-R2)

Since the number of parameters in the regression model is not taken into account by R2, as R2 is monotonic increases, the adjusted coefficient of multiple determination (Adj - R2) has been suggested as an alternative criterion. The Adj - R2 method is similar to the method and it finds the best models with the highest Adj- R2 within the range of sizes.

To determine this, we may calculate the adjusted Rsquare. This is defined as

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where MSY = SSY /( N −1) and MSE = SSE /(n − k) .

Mean Square Error MSE

The mean square error measures the variability of the observed points around the estimated regression line, and as such is an estimate of the error variance σ 2 . When using as model selection tools, one would calculate the possible subset of the predictor variables and then select the subset corresponding to the smallest value of MSE to be included to the final model.

It is defined as

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where SSE is again merely the sum squared error terms and does not take account how many observations. The smaller the value of MSE, the closer the predicted values come to the real value of respond variables.

Mallows Statistics Cp

A measure that is quite widely used in model selection is the Cp criterion measure, originally proposed by C.L. Mallows (1973). It has the form:

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where RSSp residual sum of squares from a model containing p parameters, p is the number of parameters in the model including 0 β, s2 is the residual mean square from the largest equation postulated containing all the X's, and presumed to be a reliable unbiased estimate of the error variance σ2.

R.W. Kennard (1971) has pointed out that Cp is closely related to the adjusted Rp2 and Rp2 statistic. Let us consider the relationship between adj- Rp2 or Rp2 & Cp.

Rp2 can be written as

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where SSEp being the error of squares and SST is the total sum of squares.

The adjusted coefficient of multiple determination (Adj - Rp2),

may also be considered as:

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Rp2 and adjRp2 is used for model containing only p of the K predictor variables. When the full model is used (all k predictor variables included) the following notation is used:

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and the estimate of the error variance is then given as:

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From equation (i) making SSEp the subject of the formula. It follows that

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Substitute this into Cp

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It is easily seen that Cp can be written as a function of the multiple correlation coefficient. Making (1 − Rp2) the subject of the formula from equation (3.7). It follows that in the relationship between Cp and adjR(p)2 we have

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Then from

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It is clear that there is a relationship between the adj-Rp2 or Rp2 and Cp statistics. In fact in both cases for each P the minimum Cp and the maximum adj-Rp2 or Rp2 occur for the same set of variables, although the P value of finally chosen may of course differ. The factor (n − k) in the first equation may cause decreases in minimum Cp values as P increases although Rp2 is only slowly increasing. Several authors have suggested using Cp as a criterion for choosing a model. We look for model with a small Cp and P preferably we look for a Cp close to P which means a small bias.

Forward Selection

In the forward selection procedure the analysis begins with no explanatory (independent) variables in the regression model. For each variable, a statistic called an F-statistic (F -to-enter) is calculated; this F-statistic reflects the amount of the variable’s contribution to explaining the behaviour of the outcome (dependent) variable. The variable with the highest value of the F - statistic (F-to-enter) is considered for entry into the model. If the F -statistic is significant then that variable is added to the model. If -statistic (F -to-enter) is greater than 10 or more, then explonatory variables are added to form a new current model. The forward selection procedures are repeated until no additional explanatory variables can be added [29-32].

Backward Elimination

The backward elimination method begins with the largest regression, using all possible explanatory variables and subsequently reduces the number of variables in the equation until is reached in the equation to use. For each variable, a statistic called an F -statistic (F-to-remove) is calculated. The variable with the lowest value of the F-statistic (F-to-remove) is considered for removal from the model. If the -statistic is not significant then that variable is removed from the model; if the F-statistic (F -to-remove) is 10 or less, then explanatory variables are removed to arrive at a new current model. The backward selection procedures are repeated until none of the remaining explanatory variables can be removed [33-39].

Stepwise Regression

Stepwise Regression is a combination of forward selection and backward elimination. In stepwise selection which can start with a full model, with the model containing no predictors, or with a model containing some forced variables, variables which have been eliminated can again be considered for inclusion, and variables already included in the model can be eliminated. It is important that the F-statistic (F-to-remove) is defined to be greater than the F-statistic (F-to-enter), otherwise the algorithm could enter and delete the same variable at consecutive steps. Variables can be forced to remain in the model and only the other variables are considered for elimination or inclusion.

Akaike Information Criterion (AIC)

Akaike (1973) adopted the Kullback-Leibler definition of information I(f;g), as a measure of discrepancy, or asymmetrical distance, between a “true” model f and a proposed model g, indexed on parameter vector Θ . Based on large-sample theory, Akaike derived an estimator for I(f;g) of the general form:

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where the first term tends to decrease as more parameters are added to the approximating family g(y/Θ) The second term may be viewed as a penalty for over-parameterization.

Akaike Information Criterion (AIC)

Bayesian Information Criterion (BIC) Bayesian information criterion (BIC) was introduced by Schwartz in 1978. BIC is asymptotically consistent as a selection criterion. That means, given a family of models including the true model, the probability that BIC will select the correct one approaches one as the sample size becomes large. AIC does not have the above property. Instead, it tends to choose more complex models as for small or moderate samples; BIC often chooses models that are too simple, because of its heavy penalty on complexity.

A model, which maximizes BIC is considered to be the most appropriate model.

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Where L is the maximum log likelihood, k is the number of free parameters and n is the number of independent (scalar) observation that contributes to likelihood. Model selection here is carried out by trading off lack of fit against complexity. A complex model with many parameters, having large value in the complexity term, will not be selected unless its fit is good enough to justify the extra complexity. The number of parameters is the only dimension of complexity that this method considers than AIC, BIC always provides a model with a number of parameters no greater than that chosen by AIC.

Methods

In this paper the data were partitioned into 13 sites and models fitted independently to each site. This was partially motivated during a personal discussion with Sir David Cox of the University of Oxford, who suggested that the tumours at different sites may in fact be different diseases, and therefore, may require different models for the logit of the probabilities of malignant tumours. The response variable indicated the presence of either malignant or benign tumours and is therefore a binary response. The task was now to model the probability of a malignant tumour in terms of patient age. The modern regression theory indicates that the logit of these probabilities, rather than the probabilities themselves, should be modelled either by a General Linear Model (GLM), Generalized Additive Model (GAM) or a Kernel Smooth.

At each of the 13 sites, the logit of the probabilities was modelled by increasingly flexible predictors namely: A GLM using linear or quadratic predictors, a GAM with 2, 3, and 4 degrees of freedom and a Gaussian Kernel smooth using various bandwidths, namely 8.0, 10.0 and 12.5. These are summarised in Table 1. In order to select which of the above model predictor combinations was the best at each site, we applied the model selection criteria AIC, BIC and AICc. All models were fitted using S-plus 4.0 for the purpose of assessing the models in this study. The routines for computing AIC, BIC and AICc in S-plus are given in Appendix 1 to 13. The model selection criteria, AIC, BIC and AICc were computed for each of the models described in Table 1 at each site. The model with the smallest value of AIC, BIC and AICc was then selected as the best model at a particular site. Because the Kernel smooth is a non-parametric regression without distributional assumption, it does not have a likelihood function associated with it. Because of this, the model selection criteria AIC, BIC and AICc, all of which require a likelihood, cannot be computed. We have used Kernel estimators as a non- parametric check on the best model selected from the GLM’s and GAM’s.

Table 1: Table showing the predictors that were considered for each of the various models.

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Results

This section provides a detailed analysis of site 8 (Figure1) and a summary of the best models that were fitted at each of the best sites. This was done through presentation and discussion of the fitted models using graphs (Figure 2) followed by the analysis of deviance for each of thse fitted models as shown in Table 2. Detailed statistics for the other sites are given in Appendix 1.

Figure 1: Comparison of the estimated probability model fitted at GIT.

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Figure 2: Graphs of estimated probabilities of malignant tumours for the best model at each of the13 sites using either a GLM or a GAM.

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Detailed Analysis of Site 8 (Genital Internal Track)

Consider the first row of model in Figure 2 which represents the GLM using respectively a linear, quadratic and cubic predictor i.e

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For these three models, using AIC, BIC and AICc as the model selection criteria, the GAM with 2 degrees of freedom was the selected model. In Figure 2 the first row provides a comparison of the GLM’s using a linear, quadratic and cubic predictor. Both the linear and cubic predictor appears to give similar reasonable results. The quadratic predictor, however, seems to have too much forced curvature in the left-hand corner which appears to be contrary to medical experience. The second row provides a comparison of GAM’s using 2, 3, and 4 degrees of freedom respectively. The models with 3 and 4 degrees of freedom appear to have too much force curvature. The Gaussian Kernel smooth for bandwidth of 8.0 and 10.0 shows jubias curve that cannot reflect the probabilities observed in real life. The third row provides a comparison of the three final curves selected as the best fitted model from the GLM, the GAM and the Kernel Smooth. Based on the AIC, BIC and AICc criteria we have selected the GAM with 2 degrees of freedom values that are listed below the graph. It can be seen from the graph that although this has the minimum value of AIC, it is highly constrained by linearity of the predictor. The Kernel Smooth, however, is much more flexible and therefore more able to follow the data. The Kernel Smooth also seems to indicate that the logit may not be linear.

Discussion

Central Nervous System (Figure 2). The graph conveys that the probability of a malignant tumour starts from 80% at birth and decreases to 50% at age 20. The majority of tumours are malignant primitive neuroectodermal tumours and there are few benign tumours. As the children become older, the increase in astroeytic tumours remain few.ss The model deviance is 3.5 on 2.0 degree of freedom with the p=0.174 Therefore we concluded that the model is not significant for the deviance. Head and Neck (Figure 2). It starts from 10% for infants and increases to 20% for teens. The majority of these tumours are benign haemangiomas and lymphangionias.

Very few malignant tumours occur in this area. The model deviance of 3.1 on 1 degree of freedom with a p= 0.078 which is not significant (Table 2). Therefore, the model is not significant for reducing the deviance in head and neck. Soft tissue (Figure 2) There is no change of the probability of a malignant tumour from infants to late teens. The majority of these tumours are benign, which it remains constant at 30%. Soft tissue sarcoma is rare. The commonest tumours are lymphomas and haemangiomas. The model is not significantly different from the null model of constant probability: The model deviance is 0.001 on 1 degree of freedom with a p= 0.974. Therefore, we concluded that the model is not significant for the deviance. Bone (Figure 2) The probability of a malignant tumour starts from 35% in early childhood and remains constant until age 10 and then rises steeply during the teens to 80% at age 20. Bone tumours are rare in infancy.

The sudden rise of the curve is caused by osteosarcoma which is common between the ages of 10 to 20 years. The model deviance is 13.0 on 1.9 degrees of freedom with a p= 0.001. Therefore, we concluded that the model explains a significant portion of the deviance. Kidney (Figure 2) There is a constant probability of malignant tumours close to 100% over all ages from early childhood to age 20. The malignant tumour are nephroblastomas. A few cases of congenital neuroblastic nephroma were seen in malignant tumour. The model is not significantly different from the null model of constant probability: model deviance of 0.3 on 1 degree of freedom with a p=0.584. Therefore, we concluded that the model is not significant for the deviance.

Liver (Figure 2) The probability curve starts from 95% for infants and steadily declines to 10% during the teen’s years. The malignant tumours are Hepatoblast, which is common before two years. This should explain the sudden decline of the curve because malignant tumours are indeed very high. The model deviance is 5.6 on 1 degree of freedom with a p= 0.018. Therefore, we concluded that the model explained a significant portion of deviance. Skin (Figure 2) There is a constant probability of malignant tumours close to 10% from early childhood to age 10 and this probability steadily rises to 20% during teen years. A few malignant tumours are present. The probability of contracting a malignant tumour such as Kaporis sarcoma is rare in children. The model deviance is 0.5 on 1 degree of freedom with a p= 0.479. Therefore, we concluded that the model does not explain a significant portion of deviance. Genital Internal Track (Figure 2) The graph conveys that the probability of a malignant tumour starts from 15% for infants and remains constant until age 13 and then rises steeply during the teens to 80% at age 20. This is consistent with the experience in medical practice that the probability of contracting a malignant tumour, at a very young age in the genital internal track is indeed very low and that there is a sudden rise of malignant tumours around the age of 13.

The sudden rise in the 2nd decade is caused by lymphomas. The model is strongly significant: The model deviance is 13.1 on 2 degrees of freedom with a p= 0.001. Therefore, we concluded that the model explains a significant portion of deviance. Lymph Nodes (Figure2) The probability curve starts from infants at 90% and remains constant until age 12 and then decreases during the teens to 40% at age 20. Tumours at a very young age are lymph nodes which are very high and there is a decrease of the probability curve at the age of 13. The commonest tumours were lymphomas. The model deviance is 6.9 on 2 degrees of freedom with a p=0.031 Therefore we concluded that the model explains a significant portion of deviance. Bone Marrow (Figure 2) There is a constant probability of malignant tumours close to 100% from early childhood to age 20 years of age. This resonates with the experience in medical practice that the probability of contracting malignant tumours is lymphomas and leukaemias that are found in malignant tumours. The model is not significantly different from the null model of constant probability. The model deviance is 0.4 on 1 degree of freedom with a p= 0.527. Therefore, we concluded that the model is not significant. Breast (Figure 2) The probability curve starts from 90% at birth and steadily declines from malignant to benign tumours and remains constant at 10% to late teens. There was only one malignant tumour at four years. This concurs with the experience in medical practice that the probability of contracting a malignant tumour increases after puberty and it is caused by fibroadenomas. The model is strongly significant: The model deviance is 18.0 on 2 degrees of freedom with a p= 0.0001. Therefore, we concluded that the model explains a signify, can’t portion of deviance.

Genital System (Figure 2) There is a constant probability of malignant tumours close to 40% from early childhood to age 10 and slightly decreases to 2% during teen years. A few malignant tumours are present. This is in line with the experience found in medical practice that the probability of contracting a malignant tumour is benign teratomas. The model is not significant: The model deviance is 14.9 on 1 degree of freedom with a p= 0.0001. Therefore, we concluded that the model is not significant for the deviance in genital system. Others (Figure 2) The graph indicates that the probability of a malignant tumour starts from 45% for infants and remains constant until age 13 and then rises steeply during the teens to 50% until age 20. Malignant tumour for this group of patients constitutes all those sites which did not have enough cases. This should include sites where childhood malignamies which are common, and they are rare. The model deviance is 1.5 on 1.9 degrees of freedom with a p-value of 0.448 (Table 2) Therefore, we concluded that the model is not significant for the deviance.

Table 2: Analysis of Deviance for best models at all sites.

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Conclusion and Recommendation

The problem of model selection occurs almost everywhere in statistics and we are facing more complicated data sets in the study of complex diseases. Tools that are more appropriate to the problem, more flexible to use, providing a better description, should be adopted. Model selection by AIC and BIC is one of these tools. We fitted a General Linear Model, Generalized Additive Model or Kernel Smooth using AIC and BIC model selections to the binary response to model the probability of a malignant tumour in terms of patient age. The probability of contracting a malignant tumour is consistent with the experience in medical practice and is an example of how model selections should be applied in practice. The probability distribution of the response variable was specified, and in this respect, a GAM is parametric.

In this sense they are more aptly named semi-parametric models. A crucial step in applying GAMs is to select the appropriate level of the ‘‘smoother’’ for a predictor. This is best achieved by specifying the level of smoothing using the concept of effective degrees of freedom. However, it is clear that much work still has to be done, because we have found that the Kernel smooth is a non-parametric regression which is therefore does not have likelihood function associated with it. Because of this the model selection criteria AIC and BIC, both of which require a likelihood, cannot be computed. We have used Kernel estimators as a non- parametric check on the best model selected from the GLM’s and GAM’s.

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Wednesday, 24 March 2021

Lupine Publishers| New Materials: Current Development Under Simulation Techniques

 Lupine Publishers| Modern Approaches on Material Science


Abstract

In the present short communication, a point of view on the contemporary tendencies in the development of the Science of Materials is offered. And for this, the main lines of research (personal criteria) in this area are considered, linked to problems of great importance for humanity: the care and preservation of the environment, renewable sources of energy and the health of people.

Keywords: Nanomaterials; Nanotechnology; E-skin

Introduction

In order to appreciate, in all its magnitude, the development of new materials (the totally new, the derivated, the transformed and combined ones), we need to observe through a prism of several faces, but all its converging on the plane of the climate change urgencies and the survival of the human being as a species on the planet Earth. Thus, the development of new atomic and molecular structures, the transformation of others already known, is a phenomenon closely linked to contemporary and high priority problems, such as the depletion of non-renewable sources of energy, the care and protection of the environment, and the health of people. It is possible to sustain that the emergence of modern approaches to new materials had its initial rebound in two periods of great activity: from 1821 to 1851, three decades in which it was understood at the macroscopic level and discovered the possibilities of thermoelectric; and from 1930, when it was possible to understand, from the microscopic level, thermoelectricity. This second stage led to many of the current new materials [1]. In this sense, the emergence of alternative refrigeration technologies was also decisive at the beginning of the 1990s, as a result of the combination of environmental factors and the negative evidence of global climate change. In general, the development of contemporary approaches and perspectives in the creation of new materials or the well-intentioned modification of “old” materials, is a cross-cutting phenomenon to these crucial problems of humanity, which solutions go beyond specific fields. And at the same time, in a general way, they could focus from science to suprainfim levels: nanotechnology. The manufacture of materials with great structural precision at the nanoscale has led to extremely important applications for those fields of high research demand, such as energy, environmental sciences, device technology and biomedicine. Thus, nanoarchitecture is introduced as a rising tide within the current science of nanomaterials [2]. A broad horizon, in this sense, is the discovery of graphene (“wonderful material”) and, from it, the obtaining of new two-dimensional materials such as graphyne, graphdiyne, graphone and graphane. Graphyne and graphdiyne are two-dimensional allotropes of graphene carbon with honeycomb structures. Graphone and graphane are hydrogenated derivatives of graphene. The advanced and unique properties of these new materials make them highly promising for nanoelectronics applications of next generation [3]. The already known as wonderful material has also been a bridge to reach new discoveries on principles of design and predictions of new semimetals: Dirac’s semimetals, which allow to create heterostructures from a direct layer by layer stacking, which provides an electronic coupling that facilitates a remarkable load transfer between those layers. Such structures are, apparently, very promising for the electronics of the future (Q. D. [4,5]. The material science has also managed to create crystals with optical properties that are not found in nature, whose most hopeful applications are framed in optical circuits, molecular sensors based on the resonance of surface plasmons. Comin and Manna, in their research [6] firstly explain the basic processes involved in surface plasmon resonances in nanoparticles, and later discuss the classes of nanocrystals that are particularly promising for plasmonic tunable. In the field of medicine, new materials are also playing a decisive role. For example, there are the new absorbent materials for solid phase extraction (SPE), which is the fastest growing sample preparation procedure; most usual technique in the treatment and concentration of samples before their analysis by different methods. PES are structures formed from solutions of ionic surfactants, which can be absorbed on the surfaces of active solids, resulting in sorbents capable of simultaneously extracting a wide range of analytes with an extremely varied polarity. The performance of these new SPE materials is based on molecular recognition, which mimics the selective or specific affinity of several biomolecules towards their target compounds: these absorbents include molecularly imprinted materials, immunosorbents and surfaces modified with aptamer [7]. The SPE can be considered as a giant step in the issue of obtaining samples, because the analysis of chemical compounds presents in very low concentrations in complex matrices (for example, residues and contaminants in food samples), generally requires a complex analytical approximation, involving sampling, sample preparation, isolation of analytes and qualitative and quantitative determination. In medicine, most analysts believe that the sample preparation is the Achilles heel, since it is generally time-consuming, it is prone to the introduction of contamination and it is more difficult to automate [8]. The current development of robotics is also inextricably linked to the field of medicine and novel approaches to materials. Thus, for example, the creation of an adaptable, flexible and stretchable electronic system requires the distribution of electronic products on large non-flat surfaces and mobile components. The focus of current research in this direction is marked by the use of new materials or by the intelligent engineering of traditional materials to develop new sensors, electronic components on substrates that can be wrapped around curved surfaces. Attempts are being made to achieve flexibility and elasticity in the electronic “skin”, while maintaining a reliable operation. Information about various materials that have been used in the development of flexible electronics for e-skin applications, can be found in [9]. Another current trend is the development of magnetic materials to take advantage of the magnetocaloric effect (MCE). The research focuses mainly on magnetic materials that respect the environment and their applications in heating, cooling and magnetic energy conversion technologies. However, great attention is also paid to the growing number of medical applications of the MCE, such as, for example, controllable administration and release of drugs and biomedical substances in defined places in the human body and applications of magnetic hyperthermia (cancer treatment) [10]. In the field of energy, the issue of storage is key. In studies published in 2013, electrochemical properties of materials derived from NaTi3O6 (OH) · 2H2O are revealed. The higher density and the potential for a greater speed capacity of this derivative, in comparison with the carbonaceous materials with similar voltage and reversible capacities, constitute a convincing case for its development as an anode material, both for lithium ion and sodium batteries [11]. Also, today there is a wide selection of new absorbents that can be promising for the transformation and storage of heat at low temperatures of renewable heat sources: optimization of zeolites by dealumination, further development of the aluminophosphates, the compounds “salt in the host porous matrix “, the metal-organic frames. Particular attention is focused on the chemical behavior of nano-adaptation and adjustable tuning of these materials to satisfy the demands of the appropriate cycles of heat transformation [12]. Finally, reference is made to hybrid materials, that is, materials that incorporate organic and inorganic parts. These materials have become popular in a variety of fields. The technique is not so contemporary anymore, but the incorporation of hybrid materials has given rise to a great variety of new materials and techniques to produce them. One of the most recent is the combination of the deposition of the atomic layer (ALD), which produces inorganic materials, and the deposition of the molecular layer (MLD), which produces organic materials. A variant, known as infiltration, has allowed the modification of a variety of natural and synthetic polymers with surprising results related to their general mechanical properties [13]. And what role mathematical simulation techniques has played and is playing in all the above? As has been seen, natural and artificial materials often depend on functional interfaces between organic and inorganic compounds. Examples include skeletal and biomineral tissues, drug delivery systems, catalysts, sensors, separation media, energy conversion devices and polymer nanocomposites. Current laboratory techniques are limited to monitoring and manipulating the assembly on a scale of 1 to 100nm, they are time-consuming and expensive. The confidence in the computational methods, to understand the assembly and the yield of the materials, has remarkably grown. A review of the value of the simulations compared to the experiment on the scale of 1 to 100nm, including the connections to scales of smaller length of quantum mechanics and scales of larger length of coarse-grained models, can be consulted in [14].

Conclusion

The Science of Materials, supported by its own development, and strongly “pushed upwards” by the increasing computing power, and the development of increasingly efficient and innovative simulation techniques, leads humanity towards discovery and creation of increasingly surprising materials and with a wide range of application possibilities. However, it is vitally important that such development and such possibilities do not become homicidal.

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