Demographics of the sample (
\r\n\t
",isbn:"978-1-83768-400-7",printIsbn:"978-1-83768-399-4",pdfIsbn:"978-1-83768-401-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"3e168136bc7435be0c6bbe1d7adec1f4",bookSignature:"Prof. Marwa Zakaria, Prof. Tamer Hassan and Prof. Laila Sherief",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12194.jpg",keywords:"Beta Thalassemia Major, Transfusion Dependent Beta-Thalassemia, Microcytic Hypochromic Anemia, Mutations, Beta Thalassemia Intermedia, Non-transfusion Dependent Thalassemia, Hb E Disease, Alpha Thalassemia, Genetic Counseling, Newborn Screening, Prenatal Diagnosis, Gene Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 14th 2022",dateEndSecondStepPublish:"July 12th 2022",dateEndThirdStepPublish:"September 10th 2022",dateEndFourthStepPublish:"November 29th 2022",dateEndFifthStepPublish:"January 28th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Marwa Zakaria completed her post-graduate training in Pediatric Nutrition at Boston University School of Medicine, USA. She is an Associate Professor and senior consultant of Pediatrics in the Faculty of Medicine at Zagazig University and a member of the International Society of Pediatric Oncology (SIOP), the European Hematology Association (EHA), and the Egyptian Society of Hematology.",coeditorOneBiosketch:"Professor at Zagazig University and an active member at EHA, SIOP, HAA, and ESPHO. Dr. Hassan is a guest speaker at numerous pediatric oncology and hematology meetings and he had over 50 international research publications in Pediatrics and Pediatric Hematology and Oncology.",coeditorTwoBiosketch:"Professor at Zagazig University, president of Sharkia Thalassemia Association, and member of the Egyptian national guidelines committee (NEGC) for evidence-based clinical practice. Prof. Sherief has over 50 international publications and many national publications and is an editorial board member in 17 international journals and Peer Reviewer for more than 38 international journals.",coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"187545",title:"Prof.",name:"Marwa",middleName:null,surname:"Zakaria",slug:"marwa-zakaria",fullName:"Marwa Zakaria",profilePictureURL:"https://mts.intechopen.com/storage/users/187545/images/system/187545.png",biography:"Prof. Marwa Zakaria is an Associate Professor of Pediatrics and Pediatric Hematology and Oncology, Pediatric Department, Zagazig University, Egypt. She is an active member of the International Society of Pediatric Oncology (SIOP), European Hematology Association (EHA), and Egyptian Society of Pediatric Hematology and Oncology (ESPHO). She has participated in several professional trainings and workshops, including ICH GCP online training, EHA Master Class and Bite-size Master Class, and training from the Society of Neuro-Oncology (SNO). She completed a postgraduate training program in Pediatric Nutrition at the School of Medicine, Boston University, USA, in 2017. She completed several international preceptorships, including a thalassemia preceptorship and a hemophilia preceptorship. Dr. Zakaria is the recipient of a 2018 award from SIOP, and scholarships from EHA-HOPE in 2017 and 2018. She has participated in many international and national pediatric and hematology conferences, where she has also been a guest speaker. She has more than forty international research publications in pediatrics and pediatric hematology and oncology to her credit. She has edited three books and five book chapters. She is also a reviewer for several journals, including Medicine, Frontiers in Pediatrics, Molecular Medicine Reports, International Journal of Infectious Diseases, and others. Dr. Zakaria served as co-investigator for four hematology clinical trials and sub-investigator for five others.",institutionString:"Zagazig University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}}],coeditorOne:{id:"106463",title:"Prof.",name:"Tamer",middleName:null,surname:"Hassan",slug:"tamer-hassan",fullName:"Tamer Hassan",profilePictureURL:"https://mts.intechopen.com/storage/users/106463/images/system/106463.jpg",biography:"Tamer Hassen is a Professor of Pediatrics, Faculty of Medicine, Zagazig University, Egypt. He is an active member of the European Hematology Association (EHA), International Society of Pediatric Oncology (SIOP), and Egyptian Society of Pediatric Hematology and Oncology (ESPHO), and has attended numerous national and international pediatric and hematology conferences held by these organizations and others. He has been a guest speaker at numerous pediatric oncology and hematology meetings and has published more than fifty international research publications in pediatrics and pediatric hematology and oncology. Dr. Hassan has edited two books and authored four book chapters. He has participated in many professional trainings and workshops. He received international scholarships from EHA-HOPE Cairo in 2017 and 2018, and an award from SIOP in 2016. He has completed several international preceptorships, including a hemophilia preceptorship at Saint Luc Hospital, Brussels, Belgium, and an immune-thrombocytopenia (ITP) preceptorship at Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Dr. Hassan is an editor and reviewer for many journals, including Hemophilia, Medicine, Oncology Letters, Child Neurology, and more. He was a primary investigator in four international clinical trials and a sub-investigator for ten others.",institutionString:"Zagazig University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}},coeditorTwo:{id:"110940",title:"Prof.",name:"Laila",middleName:null,surname:"Sherief",slug:"laila-sherief",fullName:"Laila Sherief",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS1HqQAK/Profile_Picture_2022-05-19T09:40:38.jpg",biography:"Professor Laila Sherief has been a long-serving member of the Zagazig University community in Egypt. She first graduated with honours from the Zagazig University and then went on to do her internship and residency there before becoming a lecturer, an Associate Professor then a Professor in Paediatric in the Faculty of Medicine. Prof. Sherief has published extensively in national/international medical journals and at medical conferences. She has over 50 international publications and many national publications and acts as a Peer Reviewer for more than 38 international journals, including Pediatric Hematology and Oncology, Pediatrics International, Journal of Coagulation & fibrinolysis, Medicine, BMC Endocrinal Disorders, Transfusion Medicine and Cancer Chemotherapy & Pharmacology. She is editorial board member in 17 international journals as BMC Pediatric, Frontiers in Genetics, Hematology case reports, Archives of hematology case reports and reviews, and Annals of Medical case reports. She supervised 83 master and MD thesis in Pediatric, Pediatric Hematology & Oncology and Clinical pathology\r\nProf. Sherief frequently attends national and international conferences and maintains memberships in many professional societies as International Society of Paediatric Oncology (SIOP), International Society of Haemostatis and Thrombosis (ISTH)., Egyptian Society of Pediatric Haematology & Oncology (ESPHO) and Egyptian Societies of thalassemia. She is the president of Sharkia thalassemia Association, Egypt, and member of the Egyptian national guidelines committee (NEGC) for evidence- based clinical practice. She was a member of the scientific committee for promotion of professors of pediatrics in the Supreme Council of Universities in Egypt from 2013 to 2016.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Zagazig University",institutionURL:null,country:{name:"Egypt"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466998",firstName:"Dragan",lastName:"Miljak",middleName:"Anton",title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/466998/images/21564_n.jpg",email:"dragan@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"52375",title:"Childhood Traumatic Experiences and Post-Traumatic Stress Disorder in Female Adults: Which is the Role Played by Romantic Attachment?",doi:"10.5772/65367",slug:"childhood-traumatic-experiences-and-post-traumatic-stress-disorder-in-female-adults-which-is-the-rol",body:'\nChildhood traumatic experiences are known to have strong and lasting consequences on the physical, mental and reproductive health of victims as well as confining them to low mental health in adulthood [1]. A body of researches largely documented the severe and long-lasting effects of the adverse childhood experiences (ACEs) on the biological and psychological development of victims [1, 2], highlighting severe impairments in stress regulation and socio-emotional development. Indeed, early interpersonal traumas expose victims to attachment disorganization and progressive deterioration in the self-worth from the first and most vulnerable stages of a child’s development [3].
\nMoreover, studies reported a significant odd-ratio for psychiatric disorders in adulthood, including major depression, panic disorder and bulimia nervosa in sexually abused victims [4]. Adults’ at-risk behaviors, such as substance abuse and dependence, are twice as common among victims, compared to the general population [5], and a major risk for sexual behaviors as well as for re-victimization is also largely documented [6–8].
\nComplex trauma, referring to children’s experiences of multiple traumatic events that occur within the caregiving system [9], has significant long-lasting effects on brain maturation. Structural and functional abnormalities are reported in abused children, namely reduction in the volume of the orbitofrontal cortex and over reactivity of the amygdala [10]. Both areas are of fundamental importance in emotional and stress responses, which display atypical functioning in abused children from the earliest stages of life [11].
\nChild maltreatment and adverse childhood experiences are a common occurrence. In 2013, 9.1 per 1000 children in the USA known to child protective services (CPS) had been victims of abuse and neglect experiences [12]. In Europe, more than 18 million children are estimated to suffer from maltreatment, as reported by the World Health Organization [13]. In particular, a prevalence of 9.6% for sexual abuse, 22.9% for physical abuse and 29.1% for mental or emotional abuse is reported. In Italy, around 9.5% per 1000 children and adolescents are subject to some form of violence in childhood [14]; the data support the international portrait.
\nOne of the most studied effects of traumatic experiences in childhood is post-traumatic stress disorder (PTSD). Post-traumatic stress disorder is classified as a “trauma and stress-related disorder” in the new Diagnostic and Statistical Manual of Mental Disorders 5 (American Psychological Association, 2013). PTSD represents the most frequent consequence of interpersonal trauma histories [15], with 48–85% of childhood abuse survivors developing PTSD symptoms across life [16, 17].
\nDespite the fact that studies have mainly analyzed only the stress-related consequences of physical and sexual traumatic experiences, emotional abuse and neglect have also been shown to be associated with the development of PTSD symptoms [18].
\nThe exposure to traumatic experiences is a necessary but not sufficient condition for the development of PTSD. According to Van der Kolk, to consider a linear relationship between early traumatic experiences and adult psychiatric disorders represents an oversimplification [19]; underlying mechanisms and victims’ characteristics involved in the association between traumatic experiences and adult psychopathology
Different studies report that psychopathological outcomes of childhood abuse are related to the quality of early attachment relationship. Around 80% of physical and emotional abuses during childhood are perpetrated by parents or close relatives [20], whom are supposed to be the primary and the first external source of emotion and stress regulation. Indeed, the parent-child relationship represents a key feature for the long-term ability of auto-regulation and social support [19, 21].
\nAccording to the attachment theory, the quality of early interactions between the caregiver and his/her child determines the child’s immediate emotional response to stress and plays a decisive and lasting role in the latter’s emotion-regulation ability [22–26]. Through the daily over-repetition of the interactive exchanges, a set of internal working models (IWMs) develops and becomes internalized as a patrimony of personal schema of self and of the other. The internal working models enable people to regulate emotions in interactions and to cope with stressful interpersonal situations across the life. These personal schemas are entirely developed during the first years of a child’s life and become relatively stable across the life span. As a consequence, they represent a personal guide influencing interactions and relationships in adulthood [27].
\nChildhood experiences of abuse and maltreatment constitute a fearful and dangerous developmental environment, in which the intimacy and proximity with the caregiver produce a sense of fear instead of a feeling of “felt security,” thus provoking a disorganization of the attachment system. Indeed, child abuse victims show significantly higher rates of attachment insecurity (70–100%) compared to the general population (30%) [28]. In addition, fearful and angry-dismissive patterns are the most associated with interpersonal traumatic experiences [29].
\nFurthermore, neglectful caregiving, even in the absence of physical and sexual abuse, denies the child the needed coherent external support. Through the inconsistent and neglectful responses of the caregiver, children develop interpersonal strategies characterized by anxious and/or avoidant behaviors [30].
\nAs a consequence, the adverse childhood experiences shape the interpersonal strategies characterizing adult relationships. In particular, high levels of dependency or avoidance in social relationship as well as insecurity, suspiciousness, isolation, emotional distress and low intimacy in close relationships are reported as a consequence of traumatic experiences [19, 31, 32]. Indeed, the core concept of the attachment theory is that childhood attachment quality constitutes the paradigm for forming the adult romantic relationship [33]. Romantic attachment represents a personal system of beliefs and expectations on the availability and the responsiveness of the partner. It is based on the childhood experiences of being loved and felt security in the relationship with the caregiver [33], and it guides the interactive exchanges between partners. People differently experience and manage intimacy with the partner according to their own early experiences of caregiver’s proximity and responsiveness. In particular, insecure adults are worried of being abandoned or being too close to and dependent on the partner [33]. According to Hazan and Shaver [33], a lack of self-worth and a negative model of self tend to produce anxiety for not being loved and being abandoned; in contrast, a negative view of the other leads to mistrust feelings, expressed by avoidant behaviors and fear of intimacy.
\nAdult and adolescent victims of abuse have higher attachment insecurity and display more anxiety and/or avoidance in close relationships [15, 34]. In particular, 70% of female victims of sexual abuse have insecure romantic attachments [35]. Lower satisfaction and couple adjustment are also reported in female victims compared to the women who were not abused [34, 36, 37]. In addition, high levels of insecurity in adult attachments and romantic attachments are reported to be associated with increased distress and psychopathology, in particular depression, anxiety, substance abuse and post-traumatic stress disorder [35, 38, 39].
\nThe attachment patterns characterized by insecure or negative IWMs seem to increase the risk of a post-traumatic stress disorder and promote post-traumatic symptoms [38, 40]. In contrast, secure attachment is reported to be a protective factor in adult trauma survivors, moderating the relationship between a traumatic event and the development of PTSD.
\nDifferent studies confirm that insecure schema of self and the other generate interpretation biases in interpersonal stressful situations. This mechanism leads to dysfunctional responses characterized by hyper-activation or deactivation of emotion regulation [30, 41]. In particular, the attachment patterns characterized by high levels of anxiety are likely to display hyper-activation of emotional and behavioral response to stress, causing an exaggerated seeking of proximity. In contrast, people with avoidant attachment deactivate the interpersonal strategies of stress response and suppress the search for support [42]. As a consequence, attachment serves as a regulatory system for the stress response; a mental representation of the other’s unresponsiveness during stressful situations can be the mechanism responsible for the increased vulnerability to post-traumatic symptoms [42].
\nIn both PTSD and insecure attachments, there is a lack of security in social and interpersonal contexts. Indeed, people suffering from PTSD report feelings of distrust and a state of anxious apprehension which impedes them from having satisfying interpersonal relationships [43].
\nAs a consequence, both the difficulties in emotion regulation and the lack of interpersonal security represent key variables in association with insecure romantic attachment and post-traumatic stress disorder in victims of childhood traumatic experiences.
\nUp until now, there are only a few studies investigating the relationship between romantic attachment and the PTSD symptoms in childhood trauma victims. Hence, further studies are needed in order to examine the role played by anxiety and avoidance on the development and the severity of the post-traumatic stress disorder in adult victims of interpersonal traumatic experiences.
\nAvailable studies in this field suggest mediating or moderating role for social support, emotion regulation and coping strategies [30]. Few studies showed that romantic attachment styles characterized by high levels of anxiety and avoidance influence the relationship between early traumatic experiences and the development of psychopathology, including post-traumatic stress disorder [44–46]. Another study [47] observed that insecure attachment mediated the relationship between childhood trauma and somatization in adulthood. Other studies [48, 49] reported that adult attachment moderates the association between childhood experiences of abuse and depressive symptoms as well as PTSD in adulthood.
\nYet, in other studies [20, 50] it was established that an association between insecure attachment and greater number of PTSD in adult women victims of child sexual abuse exists. Moreover, the ability to maintain closeness in intimate relationships is found to mediate the association between child sexual trauma and global psychological functioning [38].
\nFinally, all these studies have investigated romantic attachment in clinical samples, while no research has studied the contribution of attachment style to the association between post-traumatic stress disorder and childhood traumatic experiences in a general population [51]. This shortcoming of the available literature represents the starting point for our study.
\nThe present study aims to investigate a nonclinical sample of female students: (1) the prevalence of PTSD in adulthood; (2) the association between reported childhood traumatic experiences and the presence of post-traumatic stress disorders in adulthood and the role played by romantic attachment.
\nThe sample is composed by 327 female students from different faculties of the University of Padova: 58.4% from Psychology, 17.1% from Educational Sciences, 9.5% from International Economy, 6.7% from Social Services, 5.2% from Human Rights and Multi-Governance, 1.5% from Communication Strategies, and 1.5% from Engineering.
\nComplete demographics of the sample are displayed in Table 1.
\nThe participants were recruited on a voluntary basis and were part of a broader study on early traumatic experiences and adult psychological outcomes. All participants signed a consent form and no compensation was given for participation.
\nParticipants completed the Childhood Trauma Questionnaire-Short Form, CTQ-SF, [52] in order to assess the presence and severity of childhood traumatic experiences; the Experience in Close Relationship-Revised, ECR-R, [53] for the evaluation of the romantic attachment; and the Post-traumatic Checklist for DSM-5, PCL-5 [54] for the post-traumatic stress disorder diagnosis.
\nThe
23.09 (2.98) | \n|
\n | |
Italian | \n311 (96.3%) | \n
\n | |
Single | \n101 (31.1%) | \n
Involved | \n202 (62.2%) | \n
Living together | \n15 (4.6%) | \n
Married | \n6 (1.8%) | \n
Separated/divorced | \n1 (0.3%) | \n
Widow | \n0% | \n
\n | |
College | \n58 (17.8%) | \n
Professional high school | \n7 (2.1%) | \n
Bachelor degree | \n254 (77.9%) | \n
Master degree | \n4 (1.2%) | \n
Postgraduate degree | \n2 (0.6%) | \n
PhD | \n1 (0.3%) | \n
Demographics of the sample (
The
The
First, means, standard deviations and percentile ranks have been calculated for the distribution of PCL-5 scores, in order to attest the rate of Italian female young students showing current PTSD symptoms above the cutoff point. The PCL-5 provisional diagnosis for PTSD was established following the indication of the National Centre for PTSD
Second, in order to examine the relationship between childhood traumatic experiences, romantic attachment and current post-traumatic symptoms, correlation analyses have been preliminary done on all dimensions and scales of the three measures. Then, moderation and mediation effects have been studied. The hypotheses are displayed in Figures 1 and 2.
\nIn order to study moderation effects, a hierarchical regression analysis was built, in accordance with Baron and Kenny recommendations [60]. The interaction between predictors and moderators was created by multiplying CTQ-SF five scales and the two dimensions of ECR-R. In the Step 1, predictors (childhood traumatic experiences) and moderators (avoidance and anxiety) were entered for direct effects analyses; in Step 2, variables of the previous step were considered along with the ten interaction variables for moderating effects, as suggested by Frazier and Barron [61].
\nModeration model of childhood traumatic experiences, romantic attachment and PTSD.
Mediation model of childhood traumatic experiences, romantic attachment and PTSD.
For the mediation effect hypothesized, a path analysis was performed using LISREL 8.8 [62]. PCL-5 total score has been used as dependent variable and the five scales of the CTQ-SF as independent variables. Avoidance and anxiety in romantic attachment have been considered as mediator variables. In a first saturated model, all the five scales of the CTQ-SF were supposed to have both direct and mediated effects on the post-traumatic symptoms. Secondly, from first results, a second model has been performed including the clinical scales of CTQ-SF presenting significant direct and/or mediated effects in the first model.
\nDescriptive statistics of the variables are presented in Table 2.
Emotional Abuse | \n6.62 | \n2.601 | \n5 | \n22 | \n
Physical Abuse | \n5.42 | \n1.490 | \n5 | \n19 | \n
Sexual Abuse | \n5.29 | \n1.423 | \n5 | \n17 | \n
Emotional Neglect | \n8.92 | \n3.829 | \n5 | \n24 | \n
Physical Neglect | \n5.67 | \n1.393 | \n5 | \n16 | \n
Avoidance | \n42.13 | \n18.181 | \n8 | \n99 | \n
Anxiety | \n54.09 | \n18.832 | \n19 | \n118 | \n
Total PTSD score | \n18.21 | \n13.699 | \n0 | \n66 | \n
Table 3 shows percentile ranks of PCL-5 and the rate of subjects exceeding cutoff point for the overall PTSD measure.
9.5 | \n7 | \n15 | \n27 | \n37 | \n|
34.9% | \n
PCL-5 percentile scores.
C.O., cutoff.
*The provisional diagnosis is calculated considering: at least 1 item of Cluster B scored above 2 point; at least 1 item of Cluster C above 2;, at least 2 items above 2 in Cluster D and 2 items above 2 in Cluster E.
Table 4 presents the hierarchical regression analyses results.
\nResults from the hierarchical regression analyses showed that PTSD symptoms are significantly predicted using childhood traumatic experiences.
\nIn particular, in the Model 1, both the Emotional Abuse (β = 0.198;
As regards the romantic attachment, anxiety shows a direct effect on the post-traumatic stress symptoms, β = 0.286;
\n | ||||
---|---|---|---|---|
Emotional Abuse | \n0.198** | \n0.390 | \n0.262** | \n0.434 | \n
Physical Abuse | \n−0.136* | \n0.576 | \n−0.147* | \n0.649 | \n
Sexual Abuse | \n0.087 | \n0.530 | \n0.083 | \n0.706 | \n
Emotional Neglect | \n0.148* | \n0.245 | \n0.133 | \n0.257 | \n
Physical Neglect | \n−0.170** | \n0.631 | \n−0.178** | \n0.671 | \n
Avoidance | \n0.105 | \n0.044 | \n0.124* | \n0.046 | \n
Anxiety | \n0.286** | \n0.042 | \n0.265*** | \n0.044 | \n
Emotional Abuse × Anxiety | \n\n | \n | −0.150 | \n1.109 | \n
Emotional Abuse × Avoidance | \n\n | \n | 0.058 | \n1.051 | \n
Physical Abuse × Anxiety | \n\n | \n | 0.104 | \n1.042 | \n
Physical Abuse × Avoidance | \n\n | \n | −0.025 | \n1.383 | \n
Sexual Abuse × Anxiety | \n\n | \n | 0.079 | \n0.964 | \n
Sexual Abuse × Avoidance | \n\n | \n | −0.103 | \n1.287 | \n
Emotional Neglect × Anxiety | \n\n | \n | −0.019 | \n0.972 | \n
Emotional Neglect × Avoidance | \n\n | \n | −0.032 | \n0.989 | \n
Physical Neglect × Anxiety | \n\n | \n | 0.094 | \n1.148 | \n
Physical Neglect × Avoidance | \n\n | \n | −0.027 | \n1.174 | \n
Intercept | \n3.835 | \n3.971 | \n3.655 | \n5.110 | \n
0.227 | \n0.253 | \n
Hierarchical regression analyses: direct and moderating effect on PTSD symptoms.
*
In the Model 2, results show no moderating effects of anxiety and avoidance dimensions, with interaction variables presenting no significant weights. Among childhood traumatic experiences, Emotional Abuse (β = 0.262;
Results of the first saturated model tested show the childhood traumatic experiences to have mainly direct effects on PTSD symptoms’ severity.
\nFrom the results of the first model, a second path analysis was performed, removing Sexual Abuse and testing the direct effects of Emotional Abuse, Emotional and Physical Neglect. Moreover, in the second model, the effect of Physical Abuse and Emotional Neglect on avoidance and the effect of Physical Neglect on anxiety were tested.
\nResults of mediation analyses.
For both models, the overall fit was provided by different goodness-of-fit indices, while the path coefficients estimated the relative effect of one variable on another. The goodness-of-fit indices, following Schermelleh and colleagues [63] recommendations, were: the Non-normed Fit Index (NNFI) and the Comparative Fit Index (CFI), both ranging from 0 to 1 with values close to 1 indicating good fit. The root mean square error of approximation (RMSEA) was considered, following Browne and Cudec [64] indications, that is: ≤0.05 considered as a good fit, between 0.05 and 0.08 as an adequate fit, and between 0.08 and 0.10 as a mediocre fit, whereas values >0.10 are considered not acceptable.
\nChi-square of the second model was 6.84 df = 6;
Path coefficients indicate significant direct and mediating effects. In particular, in the second model, anxiety and avoidance mediate the effect of Emotional Neglect on PTSD (β = 0.12) and avoidance shows a tending to significance mediation of Physical Abuse on PTSD (β = −0.02;
For the direct effects, Emotional Abuse shows significant direct effect (β = 0.14) on PTSD; Physical Abuse shows no direct influence on PTSD, but a significant negative effect on avoidance (β = −0.15). Emotional Neglect has direct effect on PTSD as well as on avoidance and anxiety, respectively 0.16, 0.34 and 0.27. The Physical Neglect only fits negatively to PTSD symptoms (−0.16).
\nResults of the mediation analyses are presented in Figure 3.
\nThe first aim of this study was to explore preliminary descriptive data on the presence of significant post-traumatic symptoms in nonclinical female students attending courses at the University of Padova. Moreover, the purpose of the present study was to analyze the relationship between childhood experiences of interpersonal traumas and the presence of current post-traumatic stress disorder symptoms in an Italian sample of students. More precisely, this study tested whether romantic attachment is a significant moderator and/or mediator in the relationship between traumatic experiences and current PTSD symptoms.
\nThe first objective of the study was to provide preliminary descriptive data on PTSD in Italian female students. Although university students are considered high functioning samples, results highlight that around 10% of female students attending courses at the University of Padova exceed the cutoff point indicating a potential for the presence of post-traumatic symptoms. A high percentage of them, 34.9%, satisfy DSM-5 criteria for a provisional clinical diagnosis of post-traumatic stress disorder. This result supports the on-going investigations to assess long-term effects of childhood adverse experiences as well as other factors influencing post-traumatic manifestations.
\nWith regard to the study of a moderating effect played by anxiety and avoidance, the aim of the study was to observe whether the long-term effects of childhood traumatic experiences can be altered, namely increased, under two different conditions: higher levels of anxiety in close relationship and higher levels of avoidance of intimacy. Our results do not support this hypothesis.
\nIn the hierarchical regression, no interaction between traumas and romantic attachment significantly predicted the severity of post-traumatic symptoms. As a consequence, the present study suggests that romantic attachment is not a significant moderator in the association between childhood traumatic experiences and PTSD in adulthood. This result is in line with a recent study on the moderating role of partner emotional support and negative interaction [65], in which authors found no moderation and observed that the stress buffering theory does not explain the role of social support in distress. Our results may confirm that couple attachment does not buffer the effect of childhood trauma on post-traumatic symptoms in adulthood. However, the authors [65] suggest that further investigations should run both moderation and mediation analyses in order to have different functional understanding on the role of social support variables.
\nA previous study [50] found a moderation of the quality of romantic relationship on the association between sexual abuse experience and depression. However, methodological limitations linked to sampling and measure may account for the absence of the same result in our study.
\nDirect effects show that both anxiety and avoidance represent significant predictors of PTSD. Moreover, when all conditions are controlled, students with higher levels of emotional abuse present higher PTSD symptoms, confirming the centrality of the emotion dysregulation in the expression of post-traumatic symptoms.
\nThe physical abuse and neglect both show direct negative effects on PTSD. This result is not immediate to understand and claims for further analyses. As a consequence, functional approaches overcome the limit of descriptive interpretations of results. Finally, the variance explained by predictors and moderators suggests that other variables could be involved as independent predictors as well as significant moderators.
\nResults of the path analyses show that different forms of childhood traumatic experiences present different relationship with current post-traumatic symptoms: some forms of trauma show a direct influence on PTSD, while others are independent or have a combination of direct and indirect effects.
\nFirst, our results highlight that the inability to manage intimacy and closeness in romantic relationships leads to a severity of emotional neglect and ultimately, the development of post-traumatic symptoms in adulthood. Moreover, emotional abuse and emotional neglect display direct influences on PTSD.
\nThese results allow two considerations. First, emotional components of trauma appear to have the greatest direct and mediated influences on PTSD. In particular, a possible explanation is that emotional traumas damage or compromise the development of affect regulation in infancy; such early impairment lasts into adulthood and exposes victims to a major risk of maladaptive response in stressful situations. Moreover, the emotional abuse appears to impede interpersonal affect regulation, with victims presenting higher levels of anxiety and avoidance in romantic attachment and then greater PTSD.
\nEmotional abuse and neglect experiences are mainly expressed in chronic familiar contexts, including ignoring the child, being constantly absent, blaming, humiliating and constantly criticizing the child. These repeated experiences produce a negative self-worth and a sense of guilt which are symptoms of complex PTSD. Moreover, emotional neglect involves showing no emotions in interactive exchanges with the child which leads to extreme difficulties in recognizing self- and other-emotions. This mechanism damages the development of reliable internal model of self and other, making victims more vulnerable to high levels of anxiety and avoidance in intimate relationship.
\nSecond, the mediation of the relationship between emotional neglect and PTSD is provided by both anxiety and avoidance in romantic attachments. It is possible to suppose that previous levels of stress, due to traumatic repetitive experiences, like the inaccessibility of emotional support, can be reactivated by the vulnerability in the relationship, such as a perceived threat of abandonment. As a consequence, this mechanism might encourage people to read interpersonal minor stressors, quarrel and separations as trigger for high levels of stress, which, on the other hand, exposes hidden PTSD symptomatology. According to Van der Kolk [21], abused and maltreated children may show biases in the interpretation of interpersonal situations, quickly seeing the changes in voice tone and facial expression as a threat; consequently, they rapidly shift from the stimuli to a defensive reaction. In adulthood, this consolidated experience produces the internal perception of stress, even in neutral situation of fight or discussion in close relationships. The repetition of such mechanism produces dysregulation of emotion and hyper-arousal, characteristics of PTSD, as a response to non-stressing stimulus. A previous study shows that adult victims of childhood traumatic experiences are more likely to react with a deeper affective and physiological dysregulation to a harmless situation, compared to adult victims of a traumatic experience in adulthood [20].
\nA more controversial result is given by the negative influence of both physical abuse and neglect on post-traumatic stress disorder. Other investigations previously attested the ambiguous role of the dismissing pattern of attachment (characterized by greater avoidance) in association with PTSD. Moreover, this pattern appears to be less frequent in female samples. The two elements related to our study may affect the results. However, a possible interpretation of the results may also include that the negative emotions characterizing avoidance in romantic attachment may result in increase in emotional forms of trauma; physical abuse and neglect may have different long-terms effects, less connected with emotion regulation and PTSD. Physically abused subjects may have developed different defensive mechanisms reducing avoidance and PTSD. Further studies in this field are needed to reach a clearer interpretation.
\nFinally, the present study suggests that further investigations should consider the role of other independent predictors and other possible mediators, reported by literature, in the expression of post-traumatic symptoms and in the long-terms effects of physical interpersonal traumatic experiences.
\nThe present study has some limitations. First, for a broader and more complete understanding of the variables involved in the relationship between childhood traumas and post-traumatic symptoms, the measures of childhood experiences, attachment and psychological outcomes should include interviews and different kinds of assessment. Indeed, the present results are totally produced based on self-report measures. Second, the measure of traumatic experiences is retrospective and participants are female students; further studies should be done with clinical subjects to evaluate, in clinical or high risk groups, the role of attachment on their symptomatology. Moreover, participants were all Italians; hence, the external validity is so far limited. Another limit is due to the lack of other psychopathological outcomes which might impact on the different roles played by anxiety and/or avoidance on different psychopathologies.
\nHowever, even if methodological shortcomings of the present results do not allow clear interpretations on the role that romantic attachment may play in determining adult post-traumatic symptomatology, one of the strength of the study lays in the opportunity to describe, in a functional framework, the relationship between childhood experiences and adult post-traumatic symptomatology. Indeed, the study of both moderation and mediation overcome limits linked with descriptive models.
\nIn conclusion, the present study provides interesting results on the relationship between childhood traumatic experiences, romantic attachment and post-traumatic stress disorder, considering both the limited number of investigations involving nonclinical samples and the novelty of the application of a functional approach.
\nIn particular, the results of the present study point out the role of emotional forms of trauma in later psychopathology and well-being, evidencing the role of severe impairment of early emotional regulation on stress and socio-emotional development.
\nThe present results might be considered in a clinical framework, pointing to some aspects which should be included and focused on in the intervention with adults experiencing post-traumatic stress disorder as a result of the connection with a childhood history of abuse. From this study, we discover the role of anxiety and avoidance in close relationship as features to include in the clinical work with female victims presenting PTSD in adulthood.
\nIn particular, programs of intervention should consider focusing on affect and interpersonal regulatory skills and implement strategies addressing the work on fear of abandonment as well as on avoidance of intimacy, in order to boost more adaptive coping skills to face stressful situations. Namely, reducing the negative self-believes and/or other-believes which lead to dependence on or avoidance of the other people may reduce their hyper sensibility to stressful situation and their avoidance of negative emotion. Both features characterize affect dysregulation, interpersonal disturbance and negative self-concept typical of complex PTSD. Finally, results about the presence of PTSD among female students suggest the need for further studies and screening in general populations.
\nThroughout the ages, medicine, by inherent definition, has always been focused on the treatment of persons and individuals. Whilst the pursuit of scientific progress has inexorably propelled this process toward a systematic and harmonized approach to treatments [1], the advent of personalized medical solutions has begun to reintegrate the personalized and idiosyncratic element to the therapeutic action [2, 3]. This has erupted into a vast and expansive medical discipline in the current day, ranging from diagnostic testing [4] to tailored drug treatments [5], to the customized medical devices that will be focal here. The orthopedic customized medical device has become one of the more mundane and immediately practical manifestations of personalized medicine.
Tunneling on customized prosthetic implants such as those in use in dental, maxillofacial, and orthopedic disciplines, the dichotomy between the conventional manufacturing technologies and additive manufacturing (AM) become apparent; where subtractive manufacturing and its kin excel in excellent control of repeatability, scalability, surface finishing, and product proportions, the piecewise variation seen in personalized medical solutions levels the playing field significantly, so much so that topologies unique to additive manufacturing (AM) processes such as freeform, anatomically compliant geometries and bioinductive honeycomb porous structures are allowed to shine through [6].
That being said, there are still substantial barriers between the current state of additive manufacturing and ancillary technologies, and mature, well-characterized medical applications [7]. Medical device development has and will for the foreseeable future be driven by clinical needs, and as medical device customization continues to progress, this personalized approach brings medical professionals ever closer to the engineering-based approaches used during the design and manufacture of medical devices [8]. Operating in completely disparate paradigms, efficient bridging of this chasm will be imperative going forward [9].
Based in Hong Kong, the authors have been working toward the realization of streamlined AM utilization in the manufacture of customized medical devices over the past 5 years. Experience and involvement in the formulation of customized medical devices ranging from surgical guides and instruments to long-term orthopedic implants have culminated in a relatively refined and progressively formulaic modus operandi. Putting forth a structured workflow and robust manufacturing process validation protocols, we look to initiate discussion in the space by this proof-of-concept, not in terms of technical operational detail but the constitution of the proposed system and its potency and soundness.
A typical workflow of preparing a customized medical device consists of four stages, namely, anatomic modeling, surgical planning and design, additive manufacturing, and postprocessing, as shown in Figure 1. This workflow has been testified and applied to fabricating 11 personalized surgical instruments in Hong Kong [10].
A typical workflow of preparing a customized medical device. Stage 1: anatomic modeling. Stage 2: surgical planning and design. Stage 3: additive manufacturing. Stage 4: postprocessing.
Once clinical needs are identified, anatomical modeling is constructed based on the patient’s anatomy. Generic processes utilized during anatomical modeling are displayed in Figure 2. Computed tomography (CT) DICOM data is read as 2D grayscale pixel arrays arranged in a series of planes (Figure 2A). Desired anatomical structures are isolated on each individual array through intensity thresholding, artifacts, noise, and distortions are minimized by using image processing tools (Figure 2B). Series of 2D slice pixel arrays are interpolated and converted into a three dimensional (3D) computer-aided design (CAD)-friendly format (Figure 2C). These models and other patient information are the basis for surgical planning and design.
Stage 1: anatomic modeling, (A) scanning, (B) segmentation, and (C) construction of 3D model. Stage 2: surgical planning and design.
The surgical planning and design stage include an iterative process of (Figure 3A) surgical planning, (Figure 3B) CAD modeling, and (Figure 3C) computer-aided manufacturing (CAM) modeling, Figure 3. It requires immense communication between surgeons and engineers. The success of the design strongly depends on the level of details as well as the effectiveness of the communication of inputs from both parties. An example of surgical planning and design of a patient-specific instrument is presented in Figure 4.
Stage 2: surgical planning and design, (A) surgical planning, (B) CAD modeling, and (C) CAM modeling.
Surgical planning elements highlighted: segmented patient CT data (green) is combined with surgeon input (transparent yellow) culminating in customized surgical instrument (blue) and standardized implant (red).
Proceeding from design to manufacturing, one AM method commonly used for a metal medical device is direct metal laser sintering (DMLS) under the powder bed fusion category. In a typical DMLS setup (LUMEX Avance 25, Matsuura), additive manufacturing is achieved by repeated procedures of (Figure 5A) recoating and (Figure 5B) laser sintering. The hybrid AM approach incorporates an additional procedure of (Figure 5C) computer numerical control (CNC) machining whenever several layers are built [11]. Here, we demonstrate the DMLS method by using cobalt-chromium alloy (Figure 5). Spherical powder of size ranges from 25 μm to 40 μm (Koln3DCobaltChrome, Sandvik) is recoating onto the powder bed by a flat blade swiping sideways. The layer thickness is set at 0.4–0.5 mm whereas the laser power is set in the range of 100–400 W.
Stage 3: additive manufacturing, (A) recoating, (B) laser sintering, and (C) CNC machining.
We examine the morphology and elemental composition of cobalt-chromium alloy before and after sintering. The morphology of cobalt-chromium alloy powder observed under field emission scanning electron microscope (FESEM) is shown in Figure 6a. The powder size ranges from 25 μm to 40 μm. After laser sintering, unsintered powder remains on the surface of the built part, as shown in Figure 6b. To improve the surface finishing of the AM product, postprocessing is required. Some AM parts undergo heat treatment to improve mechanical properties such as ductility and hardness.
FESEM images. (a) Cobalt chromium alloy powder in size range of 25–40 μm. Scale bars are 100 μm (left) and 10 μm (right). (b) Surface of a part made by sintering of cobalt-chromium alloy. Scale bars are 100 μm.
Field emission scanning electron microscope/energy dispersive X-ray analysis (FESEM/EDX) was performed using an FEI Quanta 400 FEG MK2 electron microscope and an AMETEK EDAX (PV776068-ME) X-ray analyzer to investigate the composition of the samples. The back-scattered electrons (BSE) images are formed by scanning the sample with a high-energy beam of primary electrons. The primary electrons interact with the sample and generate low-energy secondary electrons and back-scattered electrons, these electrons are collected, and the surface topography of the sample can be constructed. In addition to low-energy secondary electrons, X-rays are also generated by the interaction of the primary electrons and the sample. The characteristic of X-ray emission can give qualitative elemental information of the sample. In the present case, a standardless ZAF algorithm was used for quantification.
Elemental composition measurement is performed on the powder and the sintered part. The sintered samples used in this experiment undergo heat treatment processes. Main elements, such as cobalt (Co), chromium (Cr), and molybdenum (Mo), etc., are measured by EDX. We do not observe any significant changes in the elemental composition of cobalt-chromium alloy before and after the sintering process, which are in the form of powder and sintered parts, respectively, as shown in Figure 7. The result shows that the discrepancy in elemental composition varies by within ±2 wt%.
Elemental composition of (a) cobalt-chromium alloy powder and (b) surface of the corresponding sintered part. Error bar is one standard deviation of five measurements.
Completing the AM process, postprocessing is performed for (Figure 8A) support removal and (Figure 8B) polishing according to the specific clinical needs, as illustrated in Figure 8. The postprocessing procedures are namely product-based plate detachment, support material removal, surface machining, and surface polishing. Even though a high degree of design complexity is enabled by AM technology, the low efficiency in postprocessing is a prevailing limiting factor in the entire process. To date, these postprocessing procedures are commonly conducted manually and relatively time-consuming depending on the complexity of the AM product. Recently, robotic control is introduced to automate the process and is gaining popularity in the manufacturing industry [12]. This technology is highly appealing to the medical industry for it possesses many advantages over manual operation such as higher accuracy and repeatability [13]. Full automation of robotic postprocessing systems is on its way to transforming the medical industry.
Stage 4: postprocessing, (A) support removal, and (B) polishing.
Here, we present a case study of a teenager with chondral lesions on the posterior medial quadrant of the talar dome. The treatment was performed with the aid of medial malleolar osteotomy surgical jig (Figure 9). Our proposed workflow for the preparation of additive manufacturing-assisted fabrication of medical devices has been adopted.
Case study: medial malleolar osteotomy surgical jig.
A teenager patient admitted with severe ankle pain when walking was diagnosed with abnormalities on the posterior medial quadrant of the talar dome. The suspected cause of chondral lesion is vascularization defect in subchondral talar bone. The treatment approach is laid out by (1) medial malleolus removal with the surgical jig to expose chondral lesion, (2) removal of defective chondral tissue, (3) articular surface repair, and (4) reattachment of the medial malleolus.
With patient and regulatory approval, the medical device was prepared subsequently. In the stage of anatomical modeling, a CT scan of the ankle with slice thickness 0.625 mm and slice resolution 0.5 mm was performed and the DICOM data of the talocrural joint were segmented and converted to surface mesh body. In the stage of surgical planning and device design, the chondral defect was first located. Cutting planes and fixation screw trajectories computationally were simulated and determined. Subsequently, guides for cutting planes and screw trajectories were designed, followed by patient-matched surface design according to anatomical landmarks and features coalesce to form the final design. Proceeding to the stage of additive manufacturing, the device was fabricated using a DMLS 3D printer with CoCrMo alloy (ASTM F-75 grade) powder. The process was validated with biocompatibility, mechanical, and compositional tests with critical dimensions verified. In the final stage of postprocessing, hot isostatic pressing (HIP) was performed to resolve residual stresses. After support removal, the device was ready for cleaning and packaging. The additive manufacturing-assisted fabrication of medial malleolar osteotomy surgical jig was completed.
AM-assisted fabrication of the medical device is not an automatic process. The clinical data including anatomy and functions of the body parts need to be analyzed and segmentation of the relevant parts on the data source is of paramount importance to the beginning of every AM process.
Upon arriving at a diagnosis, with confirmation through medical imaging, the anatomical and functional data will be transformed from DICOM data to stereolithography (STL) or CAD data formats interpretable by 3D printers. Engineers and clinicians will then corroboratively engage the design and customization effort. Given this approach, there are common pitfalls to take note of and avoid.
In the case of a tumor around the hip joint, combined use of CT scan and magnetic resonance imaging (MRI) can help to create accurate models for surgical planning by coregistration of two sets of DICOM. The bony margins can be defined on a CT scan, whereas the soft tissue component of the tumor and sites of tumor invasion, periosteal elevation, and/or edema within the bone are best defined on MRI. A single model created using the information from both modalities allows the surgeon to plan resection and reconstruction utilizing all available information.
The differences in pixel density (on CT scan) or signal intensity (on MRI) between immature bones and cartilage and between osteoporotic bones and osteophytes and diseased tissues can be subtle. This is particularly challenging when dealing with complex pelvic pathology. It would need manual input to delineate osteophytes and osteopenic areas and pathology areas. This means that the surgeon, radiologist, or engineer will have to manually identify, at least in part, the various anatomic structures so they can be printed as separate objects. Segmented images designated for printing patient-specific models for surgical planning should be carefully reviewed before the AM manufacturing process and validated after removal of the disease body part.
The above list of conditions is not exhaustive which can cause a fundamental error to the final product with AM manufacturing process. An accurate translation from medical needs to product innovation is safeguarded by the effective communication and information exchange between various parties involved, as discussed in Section 2.
The understanding of various materials for the additive manufacturing process impacts the functionality of the final product. Training, technical competence, and experience utilizing medical software and software for 3D printers determine the quality of the object architecture. Clinical concerns in AM technology fall into the following categories—translation from medical needs to product innovation, anatomical conformation and execution, and validation.
The medical implants for the replacement of defective parts of the human anatomy can be validated with various means. One way is to scan the resected body part and overlay it with the source data of AM [14]. This will provide a quantitative measurement of the accuracy of pre- and postmanufacturing data.
To investigate the geometric conformity of the AM parts, five distinct metallic medical devices, namely jig 1, 2, and implant 1, 2, 3, have been made from the AM approach and 3D scanned. Turntable mode on Shining 3D Einscan Pro HD 3D scanner has been used to scan robotically milled product coated with AESUB blue scanning spray. The resultant model has then been matched and analyzed with corresponding functions in the materialize MIS 24 software suite. A clinically critical zone is defined for which the geometrical accuracy is examined. Overlaying the clinical critical surface area of the design model and the scanned model, a point-to-point spatial distance is measured for each point within the clinically critical zone. The average discrepancy and the discrepancy histogram are presented in Table 1. Jig 1 yields the maximum average discrepancy of 0.13 ± 0.35 mm. For a typical computed tomography (CT) scan, the spatial and axial resolutions are 0.5 mm and 0.6 mm, which set the spatial accuracy requirement of the customized medical device. The result suggests that the AM-assisted fabrication approach attains the satisfactory special accuracy required clinically.
Robotically machined 3D-printed products were 3D scanned and compared computationally with the base CAD model. Results of the analysis are displayed.
Apart from spatial resolution, the time consumed in AM-assisted fabrication is investigated. About 11 patient-specific instruments undertaking the proposed four-stage workflow being made, including five for hallux valgus osteotomy, four for high tibial osteotomy, one each for proximal femur osteotomy, and calcaneal osteotomy. A statistic of the time taken per each stage is measured, as shown in Figure 10. Among the cases reported, the average total time taken to complete the four stages is 3.3 ± 0.6 working days. The first and last stages, that is anatomical modeling and postprocessing, are relatively routine and typically take 0.5 days to complete. Contrarily, the time is taken for surgical planning and design (Stage 2) varies. Since Stage 2 involves an iterative process requiring communication between surgeons and engineers, the time involved is not only dependent on the complexity of the design but also the effectiveness of communication between different parties. As a result, time spent on Stage 2 has been found to be the lengthiest and the most variant. The time consumed in additive manufacturing (Stage 3) is dependent on the size and resolution of the AM part. Overall, the short time frame (in the order of a few days) to fabricate metallic patient-specific instruments by AM approach has brought numerous opportunities to cater for nonemergent clinical applications, such as osteotomy as demonstrated in this work.
Time consumed per each of the four stages. Statistics of 11 cases. Error bars indicate the standard deviation.
While validation is a procedurally quintessential part of a fabrication that ensures process compatibility with intended product applications, it is especially imperative when dealing with medical devices that inherently possess the risks involved with interacting directly with human physiology. To this end, regulatory bodies such as the US Food and Drug Administration (FDA), the Chinese National Medical Products Administration (NMPA), and the decentralized regulatory authorities under the European Commission have developed medical device classification systems that categorize devices in accordance with the risk, their respective intended applications bring with them. Whilst there are nuances between the numerous classifications, medical devices are typically assessed according to their intended purpose or use, with the duration, invasiveness, reusability, sterility, and activeness being commonly scrutinized aspects that are used as indicators of the associated risk. Among medical devices, this is particularly heightened when concerning prosthetic implants that are invasive in nature and are often implicated in extremely prolonged physiological exposure during and after surgical procedures. Knowing this, validation is an exceedingly risk-dependent procedure, and as such one should always keep in mind and analyze the intended purpose or use of a product, what the associated explicit and implied product requirements are, and if and how relevant AM processes could potentially impact the conformity to these requirements.
The traditional pharmaceutical process validation structure of installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) is generally an effective methodology when transplanted into the context of AM processes. Originating from a similarly health-related industry, this does not significantly vary when being applied to the fabrication of medical devices, though there are indeed adjustments to accommodate for the aforementioned variation in associated risk inherent to the nature of the products in question. Defining the scope and breadth of the process validation will grant it greater clarity in the considerations to be made and the extent of the validation activities to be performed. While we will continue mostly focusing on hybrid additive manufacture processes (CNC-DMLS), be mindful that the type and nature of the AM processes concerned will affect the complexity of respective validation activities.
Installation qualification (IQ) is the ascertainment, through the documentation of objective evidence acquired through predefined verification methods, that all relevant equipment and machinery, whether primary, auxiliary, or ancillary, has been installed in accordance with predetermined requirements or recommendations. In practice in terms of hybrid AM processes, this typically involves infrastructural checks on items and ancillary systems such as electrical supply, compressed air supply, inert gas supply, and chiller, information that is customarily provided by most equipment manufacturers. Equipment manufacturers will also commonly have supportive services surrounding these activities in the form of complete user documentation documents as well as site acceptance tests (SAT) to qualify the commissioning of the equipment. Calibration of all measurement devices used throughout verification processes occurring during the entire validation is also usually included as part of installation qualification. IQ validation activities for the production of medical devices do not deviate from these elements, though one small detail to take note of is that the biologically oriented verification processes taking place subsequently in OQ and PQ validations might not have calibration available as it is traditionally understood. Some examples of this include the chemical assays used to determine physiological chemical characteristics and the histological examinations for assessing biological reactions toward materials. Whilst these evaluative processes are typically performed by accredited laboratories, verifications are done in-house should always have additional device accuracy verifications performed.
Operational qualification (OQ) is the process that results in the establishment of equipment operational parameters, limits, conditions, and requirements that optimally are expected to result in products meeting and product specifications. Performance qualification (PQ) builds on the findings of OQ validation, effectively stress testing the manufacturing process under simulated worst-case scenarios to ensure product specifications are met regardless, or those potential deviations and their respective rates of occurrence are acknowledged. Both OQ and PQ typically comprise a series of tests and verifications, as well as the documentation of all pertinent methodologies, results, evidence, and conclusions. Operational conditions and parameters, their control, veracity, and repeatability, are first verified to safeguard the authenticity of the test environment. In the case of hybrid AM processes, this can range from laser control parameters such as laser power and path overlap to sintering chamber environmental conditions such as oxygen concentration, build plate temperature, and enclosure temperature. This includes verification of metal powders used, as well as processes used to handle said metal powders and their respective control parameters. Once all highlighted aspects of operational control have been verified, operational limits and conditions can then be established and tests can be conducted on products produced by using operational parameters across this range, with acceptance criteria enacted based on product specifications. Through data collection and trend analysis, one can deduce and provide justification for the establishment of optimal operational parameters and conditions during product manufacture, and thus concludes OQ validation and moving on to PQ validation. In terms of hybrid AM processes, since there is not much variation when considering maximal system throughput and worst-case scenarios, PQ is often simply performed through periodically testing products manufactured at maximum printing load.
Nonmedical applications of hybrid AM processes will generally inspect for mechanical aspects such as strength and malleability, material properties such as product composition, grain structure, presence of impurities, as well as explicit elements of product specification such as product form and critical dimensions. While international standards concerning appraisal methodology of these quantities are well established from beyond the medical field, the uniqueness of medical devices applications often warrants their own testing methodology. For example, whilst bending strength and stiffness are well-characterized quantities in their own right, ISO 9585 and ASTM F382 both describe methodologies that are specific to bone plates.
In the case of medical devices, critical evaluative processes, standardized methodologies, and highly specific parameters for biocompatibility conformance have been outlined in the document series ISO 10993. In particular, Part 1 of ISO 10993 systematically outlines by flowchart all considerations necessitated by regulatory bodies when assessing the risk associated with a medical device, echoing factors previously mentioned surrounding intended use or purpose such as duration of use and invasiveness, but also taking into account the nature of physiological surfaces contacted as well as the characteristics of the device itself. Depending on the outcome of the evaluation, a range of endpoints of biological evaluation are recommended, indicating the types of tests required to demonstrate an affirmative biological evaluation (Figure 11).
Flowchart of selection of biocompatibility tests.
Critical to the case of hybrid AM processes is the stipulation that evaluation is only necessary if there is no available preexisting biocompatibility data regarding materials involved in the manufacture of the product. Whilst customized medical devices are still somewhat of a novel therapeutic solution, functionally identical or similar products have long been in use and have been extremely well-characterized biocompatibility. The same can be said for material composition, where traditionally subtractively manufactured equivalents are well defined in terms of biocompatibility. Since hybrid AM process fabricated products are homogenous and typically established metal alloys, combined with animal guidelines detailed in ISO 10993-2, it can be expected that barring medical devices where material properties are completely novel with no biocompatibility data, most hybrid AM products will only require physical and chemical characterization, as well as cytotoxicity.
On the flip side, if the application and/or material in use is truly novel with insufficient precedent data for biocompatibility evaluation, a wide range of costly
Device type | Biological contact | Length of contact | ISO standard for tests required | ||||||
---|---|---|---|---|---|---|---|---|---|
ISO 10993-18 | ISO 10993-19 | ISO 10993-5 | ISO 10993-10 | ISO 10993-11 | ISO 10993-6 | ISO 10993-3 | |||
Implant | Tissue/bone | <24 h | × | × | × | × | |||
24 h<, <30 days | × | × | × | × | o | × | o | ||
>30 days | × | × | × | × | o | × | o | ||
External brace | Intact skin | <24 h | × | × | × | × | |||
24 h<, <30 days | × | × | × | × | |||||
>30 days | × | × | × | × |
Biocompatibility tests required for 2 types of example medical devices.
×: tests in ISO standard are recommended if no preexisting marketed equivalents exist.
o: particular tests in ISO standard are recommended if no preexisting marketed equivalents exist.
As personalized medical solutions popularize across the globe, there has been a scramble from regulatory bodies in bringing patient-conforming medical devices under the scope of preexisting regulative structure. Given the uniqueness of certain anatomical features and the significant interpersonal variation that exists, by definition, these medical devices will have noticeable differences on a piece-by-piece basis. This results in increased difficulty in quality control and subsequently, regulation since these devices intrinsically are never completely identical and thus one cannot demonstrate conformance to regulatory requirements through a sample device in the present when every following iteration of the device will inherently be different, with variation often being guided by the anatomical features of patients. To this end, regulators have taken similar, risk-based approaches in incorporating these elements into their respective frameworks. The discussion will focus on the globally preeminent regulatory bodies of USFDA and the national regulatory bodies under the European Commission, as well as the locally relevant NMPA of China.
Personalized medical devices are generally split into three groups of products by regulatory bodies, based on the resemblance of their respective intended uses and manufacturing models with conventional, mass-produced medical devices that regulatory bodies devise their systems around. Here, we must part with the terminology of “Customized Medical Device” in favor of more precise language. The first group is referred to as adaptable medical devices (AMD) and are personalized medical devices that are mass manufactured as a series of compatible components and assemblies, only to be tailored to the patient’s unique requirements at the point of care, by medical professionals in accordance with their medical judgment as well as device guidelines. They are essentially mass-produced products with an element of personalization in their intended use and are usually treated as such by regulatory bodies, simply following standard device classification protocols to determine regulatory requirements. In fact, the European Medical Device Regulation (EU MDR), FDA, and NMPA all do not implement additional regulatory procedures with respect to this type of device. Some AM-produced products make use of this ease of control and regulation, where the device is comprised of standardized, mass-produced parts as well as a relatively small AM-produced component that conforms to a subsection of patient anatomy that typically sees greater variation and hence requires personalization [16].
The second group is described as patient-matched medical devices (PMD) and are characterized by a largely identical manufacturing process, as well as a design envelope that encapsulates and bounds potential design features, including patient-specific features, and their potential variation. Significant portions of AM-produced medical devices will fall under this category, with products that have slightly adaptive if not harmonized intended uses, indications, contraindications, and design envelopes, that are essentially functionally identical but are designed to cater to differing individual anatomies. The classification of PMDs is an adaptation that regulatory bodies have utilized in incorporating personalized medical devices, and by proxy AM products, into a simpler regulatory framework, where these devices are generally viewed in a similar fashion as conventional medical devices but may require additional documentation, justifications, and design controls to compensate for the increased risk brought on by potential variations in design. The NMPA, EU MDR, and FDA do not have any additional regulatory requirements with respect to “Patient-Matched Medical Devices,” however, the FDA has developed and issued a guidance document titled “Technical Considerations for Additive Manufactured Medical Devices” in 2017, such that whilst there is no additional explicit requirement, there is a baseline of expectation when putting forth AM products that the FDA assumes [17].
The final category is the most original and authentic to the idea of personalized medicine, that being custom-made medical devices (CMD). This refers to devices that, at the request or prescription of a medical professional, are truly made for only one particular individual and is generally targeted toward extremely rare conditions where it is unfeasible to market the device or high specific conditions where no singular adaptive design envelope could realistically cover all facets of device. As a result of this distinctive product design and intended use, the manufacturing process is often unique in its entirety. Curiously the definition extends from devices tailored toward patients to devices catering to the medical professionals treating the patient. Owing to its inherently flexible nature, AM processes are often involved in the production of these devices, foremost being custom-made orthopedic implants. To date most regulatory bodies have implemented special exemptions and requirements to allow the use of these devices, conceding that truly customized devices will have to be evaluated and accounted for outside the general regulatory system. Annex IX [18] within the EU MDR has very clear requirements for CMDs, that a specific statement shall be prepared for all CMDs expressing key information, as well as other ancillary requirements. The EU MDR also states that Class III implantable “Custom-Made Medical Devices” shall additionally be subject to the typical conformity assessment. Meanwhile, the NMPA regulates CMDs less stringently, where “Custom-Made Medical Devices” are allowed for use after notification with key information is sent and acknowledged by regulatory authorities, with the precondition that the CMDs is to undergo standard market clearance and approval as soon as clinical data and feedback following the initial utilizations allow for the registration of the CMD (Table 3) [19, 20].
CMD | PMD | AMD | |
---|---|---|---|
Intended use | Intended for use only for a particular individual (including medical professionals), to address specific feature or condition of the said target individual | Intended for use on the specific patient, with certain features matched with said patient’s anatomical data, done so according to the design envelope. | Intended for general use, with device personalized during the application, according to assembly instructions |
Prescription | Mandatory | Not mandatory | Not mandatory |
Design responsibility | Doctor, under manufacturer consultation | Manufacturer, under doctor consultation | Manufacturer |
Production | Unique, tailored | Repeated validated process, possibly in batches | Mass produced |
EU MDR regulatory requirements | Statement (Annex XIII) + conformity assessment (Annex IX/Annex XI)—Class III implantable devices only | Conformity assessment (Annex IX/Annex XI) | Conformity assessment (Annex IX/Annex XI) |
US FDA regulatory requirements | Custom device exemption (FD&C act section 520(b) + requirements) + QS regulation (CFR title 21) | PMA (Class III/Class II), 510(k) approval (Class I/Class II) | PMA (Class III/Class II), 510(k) approval (Class I/Class II) |
CN NMPA regulatory requirements | Notification to regulatory body for initial cases undergo standard market clearance/approval as soon as possible | Standard market clearance/approval: Pre-market notification (Class I) Pre-market registration (Class II+) | Standard market clearance/approval: Pre-market notification (Class I) Pre-market registration (Class II+) |
Personalized medical device classification and regulatory requirements.
All information is highly generalized and will deviate from product to product.
The demand for a customized medical device is at an all-time high. Thanks to the accuracy and variety of form and function to attain intended biomechanical function with adequate biocompatibility, AM-assisted fabrication has profound advantages in clinical flexibility. This work has demonstrated with examples a framework of AM-assisted fabrication of metallic medical devices serving intended clinical needs within a suitable time frame. The AM-assisted fabrication platform established is potentially utilizable with synthesized biomaterials and pharmaceutics [21]. Opportunities are gravitating to surgeons and researchers navigating to efficacious outcomes in clinical applications.
SYM acknowledges funding support from sponsored research RS 200263 at the University of Hong Kong.
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For macroscopic characterization, three properties of the material are often tested: complex permittivity, complex permeability and conductivity. Based on the experimental setup and sub-principle of measurements, microwave measurement techniques can be categorized into either resonant technique or nonresonant technique. In this chapter, calibration procedures for non-resonant technique are described. The aperture of open-ended coaxial waveguide has been calibrated using Open-Short-Load procedures. On the other hand, the apertures of rectangular waveguides have been calibrated by using Short-Offset-Offset Short procedures and Through-Reflect-Line calibration kits. Besides, the extraction process of complex permittivity and complex permeability of the material which use the waveguide systems is discussed. For one-port measurement, direct and inverse solutions have been utilized to derive complex permittivity and complex permeability from measured reflection coefficient. For two-port measurement, in general, the material filled in the waveguide has been conventional practice to measure the reflection coefficient and the transmission coefficient by using Nicholson-Ross-Weir (NRW) routines and convert these measurements to relative permittivity, εr and relative permeability, μr. In addition, this chapter also presents the calculation of dielectric properties based on the difference in the phase shifts for the measured transmission coefficients between the air and the material.",book:{id:"5436",slug:"microwave-systems-and-applications",title:"Microwave Systems and Applications",fullTitle:"Microwave Systems and Applications"},signatures:"Kok Yeow You",authors:[{id:"188673",title:"Dr.",name:"Kok Yeow",middleName:null,surname:"You",slug:"kok-yeow-you",fullName:"Kok Yeow You"}]},{id:"53096",doi:"10.5772/66361",title:"Multiple Person Localization Based on Their Vital Sign Detection Using UWB Sensor",slug:"multiple-person-localization-based-on-their-vital-sign-detection-using-uwb-sensor",totalDownloads:2007,totalCrossrefCites:7,totalDimensionsCites:16,abstract:"In the past period, great efforts have been made to develop methods for through an obstacle detection of human vital signs such as breathing or heart beating. For that purpose, ultra-wideband (UWB) radars operating in the frequency band DC-5 GHz can be used as a proper tool. The basic principle of respiratory motion detection consists in the identification of radar signal components possessing a significant power in the frequency band 0.2–0.7 Hz (frequency band of human respiratory rate) corresponding to a constant bistatic range between the target and radar. To tackle the task of detecting respiratory motion, a variety of methods have been developed. However, the problem of person localization based on his or her respiratory motion detection has not been studied deeply. In order to fill this gap, an approach for multiple person localization based on the detection of their respiratory motion will be introduced in this chapter.",book:{id:"5436",slug:"microwave-systems-and-applications",title:"Microwave Systems and Applications",fullTitle:"Microwave Systems and Applications"},signatures:"Daniel Novák, Mária Švecová and Dusan Kocur",authors:[{id:"83173",title:"Dr.",name:"Dusan",middleName:null,surname:"Kocur",slug:"dusan-kocur",fullName:"Dusan Kocur"},{id:"189768",title:"MSc.",name:"Daniel",middleName:null,surname:"Novák",slug:"daniel-novak",fullName:"Daniel Novák"},{id:"189769",title:"Dr.",name:"Mária",middleName:null,surname:"Švecová",slug:"maria-svecova",fullName:"Mária Švecová"}]},{id:"10352",doi:"10.5772/9061",title:"Dielectric Anisotropy of Modern Microwave Substrates",slug:"dielectric-anisotropy-of-modern-microwave-substrates",totalDownloads:3061,totalCrossrefCites:3,totalDimensionsCites:14,abstract:null,book:{id:"3707",slug:"microwave-and-millimeter-wave-technologies-from-photonic-bandgap-devices-to-antenna-and-applications",title:"Microwave and Millimeter Wave Technologies",fullTitle:"Microwave and Millimeter Wave Technologies from Photonic Bandgap Devices to Antenna and Applications"},signatures:"Plamen I. Dankov",authors:null},{id:"9964",doi:"10.5772/8747",title:"Physics of Charging in Dielectrics and Reliability of Capacitive RF-MEMS Switches",slug:"physics-of-charging-in-dielectrics-and-reliability-of-capacitive-rf-mems-switches",totalDownloads:5103,totalCrossrefCites:8,totalDimensionsCites:14,abstract:null,book:{id:"3623",slug:"advanced-microwave-and-millimeter-wave-technologies-semiconductor-devices-circuits-and-systems",title:"Advanced Microwave and Millimeter Wave Technologies",fullTitle:"Advanced Microwave and Millimeter Wave Technologies Semiconductor Devices Circuits and Systems"},signatures:"George Papaioannou and Robert Plana",authors:null},{id:"10350",doi:"10.5772/9059",title:"Millimeter-Wave Imaging Sensor",slug:"millimeter-wave-imaging-sensor",totalDownloads:4989,totalCrossrefCites:9,totalDimensionsCites:10,abstract:null,book:{id:"3707",slug:"microwave-and-millimeter-wave-technologies-from-photonic-bandgap-devices-to-antenna-and-applications",title:"Microwave and Millimeter Wave Technologies",fullTitle:"Microwave and Millimeter Wave Technologies from Photonic Bandgap Devices to Antenna and Applications"},signatures:"Masaru Sato and Koji Mizuno",authors:null}],mostDownloadedChaptersLast30Days:[{id:"58958",title:"Introductory Chapter: RF/Microwave Applications",slug:"introductory-chapter-rf-microwave-applications",totalDownloads:1449,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"6318",slug:"emerging-microwave-technologies-in-industrial-agricultural-medical-and-food-processing",title:"Emerging Microwave Technologies in Industrial, Agricultural, Medical and Food Processing",fullTitle:"Emerging Microwave Technologies in Industrial, Agricultural, Medical and Food Processing"},signatures:"Kok Yeow You",authors:[{id:"188673",title:"Dr.",name:"Kok Yeow",middleName:null,surname:"You",slug:"kok-yeow-you",fullName:"Kok Yeow You"}]},{id:"53062",title:"Materials Characterization Using Microwave Waveguide System",slug:"materials-characterization-using-microwave-waveguide-system",totalDownloads:3098,totalCrossrefCites:13,totalDimensionsCites:20,abstract:"This chapter reviews the application and characterization of material that uses the microwave waveguide systems. For macroscopic characterization, three properties of the material are often tested: complex permittivity, complex permeability and conductivity. Based on the experimental setup and sub-principle of measurements, microwave measurement techniques can be categorized into either resonant technique or nonresonant technique. In this chapter, calibration procedures for non-resonant technique are described. The aperture of open-ended coaxial waveguide has been calibrated using Open-Short-Load procedures. On the other hand, the apertures of rectangular waveguides have been calibrated by using Short-Offset-Offset Short procedures and Through-Reflect-Line calibration kits. Besides, the extraction process of complex permittivity and complex permeability of the material which use the waveguide systems is discussed. For one-port measurement, direct and inverse solutions have been utilized to derive complex permittivity and complex permeability from measured reflection coefficient. For two-port measurement, in general, the material filled in the waveguide has been conventional practice to measure the reflection coefficient and the transmission coefficient by using Nicholson-Ross-Weir (NRW) routines and convert these measurements to relative permittivity, εr and relative permeability, μr. In addition, this chapter also presents the calculation of dielectric properties based on the difference in the phase shifts for the measured transmission coefficients between the air and the material.",book:{id:"5436",slug:"microwave-systems-and-applications",title:"Microwave Systems and Applications",fullTitle:"Microwave Systems and Applications"},signatures:"Kok Yeow You",authors:[{id:"188673",title:"Dr.",name:"Kok Yeow",middleName:null,surname:"You",slug:"kok-yeow-you",fullName:"Kok Yeow You"}]},{id:"52960",title:"On-Wafer Microwave De-Embedding Techniques",slug:"on-wafer-microwave-de-embedding-techniques",totalDownloads:3551,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Wireless communication technology has kept evolving into higher frequency regime to take advantage of wider data bandwidth and higher speed performance. Successful RF circuit design requires accurate characterization of on-chip devices. This greatly relies on robust de-embedding technique to completely remove surrounding parasitics of pad and interconnects that connect device to measurement probes. Complex interaction of fixture parasitic at high frequency has imposed extreme challenges to de-embedding particularly for lossy complementary metal oxide semiconductor (CMOS) device. A generalized network de-embedding technique that avoids any inaccurate lumped and transmission line assumptions on the pad and interconnects of the test structure is presented. The de-embedding strategy has been validated by producing negligible de-embedding error (<−50 dB) on the insertion loss of the zero-length THRU device. It demonstrates better accuracy than existing de-embedding techniques that are based on lumped pad assumption. For transistor characterization, the de-embedding reference plane could be further shifted to the metal fingers with additional Finger OPEN-SHORT structures. The resulted de-embedded RF parameters of CMOS transistor show good scalability across geometries and negligible frequency dependency of less than 3% for up to 100 GHz. The results reveal the importance of accounting for the parasitic effect of metal fingers for transistor characterization.",book:{id:"5436",slug:"microwave-systems-and-applications",title:"Microwave Systems and Applications",fullTitle:"Microwave Systems and Applications"},signatures:"Xi Sung Loo, Kiat Seng Yeo and Kok Wai, Johnny Chew",authors:[{id:"189098",title:"Dr.",name:"Xi Sung",middleName:null,surname:"Loo",slug:"xi-sung-loo",fullName:"Xi Sung Loo"},{id:"189214",title:"Prof.",name:"Kiat Seng",middleName:null,surname:"Yeo",slug:"kiat-seng-yeo",fullName:"Kiat Seng Yeo"},{id:"189215",title:"Dr.",name:"Kok Wai, Johnny",middleName:null,surname:"Chew",slug:"kok-wai-johnny-chew",fullName:"Kok Wai, Johnny Chew"}]},{id:"52747",title:"Nonlinear Channel Equalization Approach for Microwave Communication Systems",slug:"nonlinear-channel-equalization-approach-for-microwave-communication-systems",totalDownloads:2215,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The theoretical principles of intersymbol interference (ISI) and channel equalization in wireless communication systems are addressed. Several conventional and well-known equalization techniques are discussed and compared such as zero forcing (ZF) and maximum likelihood (ML). The main section in this chapter is devoted to an abstract concept of equalization approach, namely, dual channel equalization (DCE). The proposed approach is flexible and can be employed and integrated with other linear and nonlinear equalization approaches. Closed expressions for the achieved signal-to-noise ratio (SNR) and bit error rate (BER) in the case of ZF-DCE and ML-DCE are derived. According to the obtained outcomes, the DCE demonstrates promising improvements in the equalization performance (BER reduction) in comparison with the conventional techniques.",book:{id:"5436",slug:"microwave-systems-and-applications",title:"Microwave Systems and Applications",fullTitle:"Microwave Systems and Applications"},signatures:"Modar Shbat, Francisco Ordaz-Salazar and Javier Salvador González-Salas",authors:[{id:"189618",title:"Prof.",name:"Modar",middleName:null,surname:"Shbat",slug:"modar-shbat",fullName:"Modar Shbat"},{id:"189620",title:"Prof.",name:"Francisco",middleName:null,surname:"Ordaz-Salazar",slug:"francisco-ordaz-salazar",fullName:"Francisco Ordaz-Salazar"},{id:"189621",title:"Prof.",name:"Javier Salvador",middleName:null,surname:"González-Salas",slug:"javier-salvador-gonzalez-salas",fullName:"Javier Salvador González-Salas"}]},{id:"60385",title:"Fractal Array Antennas and Applications",slug:"fractal-array-antennas-and-applications",totalDownloads:1235,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Modern celestial and other advanced wireless communication systems require feasible array antennas with reconfigurable multibeams, broadband, high end of coverage, high gain, less side-lobe level with wider side-lobe level angles, better signal-to-noise ratio and small in size than conventionally achievable. This has initiated array antenna research in different tracks, one of which is by using fractal array antennas. The investigation on fractal-shaped antennas is basically focused on two fundamental areas such as the analysis and design of fractal antenna elements and the application of fractal geometric technology to the design of array antennas. These recursively generated antennas provide new insights into the antenna properties due to their self-similar behaviour. Owing to the feasible geometric construction and advanced properties, fractal antennas find applications in advanced wireless communications, MIMO radars, satellite communications and space observations. This work concentrated here is primarily aimed on the design of fractal array antennas using concentric elliptical ring sub-array fractal geometric design methodology and the reduction of total number of antenna elements at higher expansion factors of both conventional and proposed fractal array antennas.",book:{id:"6318",slug:"emerging-microwave-technologies-in-industrial-agricultural-medical-and-food-processing",title:"Emerging Microwave Technologies in Industrial, Agricultural, Medical and Food Processing",fullTitle:"Emerging Microwave Technologies in Industrial, Agricultural, Medical and Food Processing"},signatures:"V. A. Sankar Ponnapalli and P. V. Y. Jayasree",authors:[{id:"210988",title:"Dr.",name:"V.A.Sankar",middleName:null,surname:"Ponnapalli",slug:"v.a.sankar-ponnapalli",fullName:"V.A.Sankar Ponnapalli"},{id:"210989",title:"Prof.",name:"V. Y. Jayasree",middleName:null,surname:"Pappu",slug:"v.-y.-jayasree-pappu",fullName:"V. Y. Jayasree Pappu"}]}],onlineFirstChaptersFilter:{topicId:"750",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82123",title:"Microwave-Assisted Pyrolysis Process: From a Laboratory Scale to an Industrial Plant",slug:"microwave-assisted-pyrolysis-process-from-a-laboratory-scale-to-an-industrial-plant",totalDownloads:36,totalDimensionsCites:0,doi:"10.5772/intechopen.104925",abstract:"One of the great challenges for the European Union (EU) is the “Circular Economy Package,” and to achieve this goal, materials at the end of their life cycle must be recycled using a sustainable process. In this way, as a thermochemical treatment, pyrolysis represents a significant opportunity so long it leads to the recovery of both energy and chemical content of mixed, contaminated, or deteriorated plastics. An excellent history of an academic-industrial adventure started in 2008 at the Department of Chemistry of the University of Florence demonstrates the possibility of employing microwaves to recycle plastics to preserve their energy and chemical content. After that, Techwave started industrialization of the process in 2019, realizing a small-scale prototype followed by a full-scale pilot plant using different plastic materials (e.g., polystyrene, acrylonitrile-butadiene-styrene (ABS), and polypropylene). Nowadays, the plant may process 90 kg/h of plastics with a low formation of char and gas and an interesting amount of liquid useful as a source of chemicals or fuel because it has an LHV of 35–43 kJ/kg. The Microwave-Assisted Pyrolysis (MAP) is an industrial novelty in plastic recycling, and it looks very promising for a much more modern and innovative plastic waste recovery system.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Marco Frediani, Piero Frediani, Gianni Innocenti, Irene Mellone, Roberto Simoni and Gianpaolo Oteri"},{id:"82420",title:"Applications of Microwaves in Medicine and Biology",slug:"applications-of-microwaves-in-medicine-and-biology",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.105492",abstract:"This chapter deals with the description of recent research activities oriented on the perspective of microwave technologies in medicine and biology. It brings new ideas about the possibilities of using microwaves in thermotherapy—above all toward hyperthermia in cancer treatment. Development of new types of hyperthermia applicators (based, e.g., on technologies such as metamaterials, evanescent modes in waveguides, and other types of transmission structures) will be discussed here. Furthermore, we would like to underline in this chapter perspectives of microwaves in medical diagnostics. It is possible to expect that, e.g., microwave differential tomography, UWB radar, and microwave radiometers (all three can be used both for medical diagnostic and for noninvasive temperature measurement) will soon play an important role in it. Finally, experimental equipment necessary for research on the biological effects of EM fields is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"David Vrba, Jan Vrba, Ondrej Fiser, Jesus Cumana, Milan Babak and Jan Vrba Senior"},{id:"81917",title:"Fluidics for Reconfigurable Microwave Components",slug:"fluidics-for-reconfigurable-microwave-components",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104857",abstract:"Dielectric and conducting liquids with varying electromagnetic properties can offer novel alternatives for building tunable microwave passive components as well as antennas. Injecting these fluidics in or around microwave substrates alters their overall electrical characteristics, enabling circuit reconfigurability. Alternatively, changing the shapes and dimensions of conductors by using liquid metals can achieve similar reconfigurability. An overview of different liquids and their electromagnetic properties is first given. The principles behind the reconfigurability of the electrical characteristics of typical guiding structures based on mode shape variation in the presence of fluids are discussed. The realization of an N-bit programmable impedance tuner in 3D LTCC technology based on these principles is presented.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Dorra Bahloul, Ines Amor and Ammar Kouki"},{id:"82046",title:"One Model of Microwave Heating of Water Drop",slug:"one-model-of-microwave-heating-of-water-drop",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.104949",abstract:"This work deals with the modeling of microwave heating of a water drop. A drop model is reduced to its electric dipoles, masses, and charges are constructed using the associating of COMSOL Multiphysics and Matlab software. The considered model proposes a microscopic point of view on microwave heating, which transforms electrical energy into heat.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Serge Lefeuvre and Olga Gomonova"},{id:"82076",title:"Power Divider/Combiner",slug:"power-divider-combiner",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.104911",abstract:"With the remarkable progress in the use of Internet of Things (IoT) and 5G, there is a demand for higher performance such as miniaturization, broadband/multiband, low loss, and high integration for several microwave circuits. This chapter treats microwave power dividers/combiners used in amplifiers, mixers, phase shifters, antenna feeding networks, and so on. Here, the treated circuits are composed of LC-ladder circuits and an absorption resistor. It shows that multiband (dual-band and tri-band) and broadband can be achieved by changing the number of stages of the LC-ladder circuit. In addition, the effectiveness of this design method is demonstrated by electromagnetic simulations and prototype experiments.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Tadashi Kawai, Ayumu Tsuchiya and Akira Enokihara"},{id:"82035",title:"Orbital Angular Momentum Wave and Propagation",slug:"orbital-angular-momentum-wave-and-propagation",totalDownloads:38,totalDimensionsCites:0,doi:"10.5772/intechopen.104477",abstract:"Orbital angular momentum (OAM) techniques are exploited for a wide range of potential radiofrequency (RF) and electromagnetic applications, including megahertz-through-terahertz wireless systems, fiber-based and free-space optical communications and sensing, just like acoustic and any other wave-based counterparts. In those RF and electromagnetic applications, OAM wave is set to enable the development of high-speed and high-capacity communications, radar imaging, and sensing systems, among many others. In this chapter, a comprehensive comparison between plane wave and OAM wave propagation using a patch antenna as a radiator at 2.45 GHz is presented and discussed. This comparison allows the appreciation of the fundamental properties of the OAM wave when compared against its plane wave counterpart. For simplified comparison and discussion, we will use two abbreviated terms: PWPA for plane-wave patch antenna and OWPA for OAM wave patch antenna. PWPA refers to as planar patch antenna that produces plane waves in far-field, whereas patch antenna that delivers OAM waves in far-field is termed as OWPA. In this context, all physical quantities for wave propagation such as electric field, magnetic field, wave impedance, wave vector, velocity, pitch, and propagation constant are theoretically studied for OAM waves and compared with plane waves. First, OAM wave generation is studied through widely used uniform circular antenna array (UCAA) in literature. Then, plane wave patch antenna (PWPA) and OAM wave patch antenna (OWPA) are designed and verified through simulation and measurement. OWPA is designed with characteristic mode analysis (CMA) based on a lossy substrate to excite a twisting wave at a determined patch location. With this in mind, a comparative investigation of PWPA and OWPA is conducted for different physical parameters. Cylindrical near-field scan clearly shows a helical wave motion for OWPA, whereas a normal plane wave motion for PWPA. Furthermore, the comparison of plane wave and OAM wave propagation is demonstrated using the combination of a Tx–Rx antenna pair. It is observed that the overall signal from OWPA can be received with two PWPAs at an angle as OWPA has a dispersive beam. Moreover, the receiving antenna with a large aperture and plane wave horn antenna (PWHA) in the line of sight (LOS) range can also be used to receive the overall signal from OWPA. The received signal in PWPA–PWPA, OWPA–OWPA, OWPA–PWPA–PWPA, OWPA–PWHA Tx–Rx pairs is thoroughly compared and studied. Measured and simulated results for transmission are −30 dB for 0 dB input signal in OWPA–PWPA–PWPA and OWPA–PWHA cases, which are reasonably justified within the sensitivity/dynamic range of short-distance communication and radar sensing receivers.",book:{id:"11145",title:"Recent Microwave Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11145.jpg"},signatures:"Pankaj Jha and Ke Wu"}],onlineFirstChaptersTotal:14},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Singh",profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8018",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",slug:"extracellular-matrix-developments-and-therapeutics",publishedDate:"October 27th 2021",editedByType:"Edited by",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",hash:"c85e82851e80b40282ff9be99ddf2046",volumeInSeries:23,fullTitle:"Extracellular Matrix - Developments and Therapeutics",editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",institutionString:"Illinois Institute of Technology",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:4},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:9},{group:"subseries",caption:"Chemical Biology",value:15,count:14}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:9},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:303,paginationItems:[{id:"280338",title:"Dr.",name:"Yutaka",middleName:null,surname:"Tsutsumi",slug:"yutaka-tsutsumi",fullName:"Yutaka Tsutsumi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/280338/images/7961_n.jpg",biography:null,institutionString:null,institution:{name:"Fujita Health University",country:{name:"Japan"}}},{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. 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