Self-employment rates (Eurostat Labour Force Survey). Note: Percentage of self-employed persons over total employed.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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\r\n\tThis book aims to explore the various management strategies for facial and dental anomalies which include both surgical and non-surgical orthopedic interventions. Treatments like craniofacial and orthognathic surgery are critical not only in addressing skeletal malocclusion but also in the management of obstructive sleep apnea, facial cosmetics, orthodontic discrepancies, cleft and craniofacial deformities, post-traumatic dentofacial asymmetry, and temporomandibular joint disorders.
\r\n\r\n\tThe craniomaxillofacial skeleton consists of multiple intricate and distinct but co-functioning units. Corrective measures are typically multi-disciplinary in approach, requiring the skills of experienced providers in plastic surgery, otolaryngology, oral and maxillofacial surgery, sleep medicine, orthodontics, and dentistry. Thus, the text itself is meant to be an inter-professional collaboration of providers from a variety of specializations.
\r\n\r\n\tWe hope to create a book that is relevant not only across medical disciplines but across ethnicities as well. To this end, we welcome experts from across the globe to help ensure that the information contained within remains universal.
",isbn:"978-1-80356-483-8",printIsbn:"978-1-80356-482-1",pdfIsbn:"978-1-80356-484-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"413b0d1441beac767fe0fbf7c0e98622",bookSignature:"Dr. H. Brian Sun",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11691.jpg",keywords:"Skeletal Malocclusion, Overbite, Underbite, Orthodontics, Surgery-First, Maxillo-Mandibular Discrepancy, Congenital Facial Asymmetry, Cleft Lip, Traumatic Malocclusion, Traumatic Asymmetry, Fracture Line Osteotomy, Le Fort Fracture",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 3rd 2022",dateEndSecondStepPublish:"March 31st 2022",dateEndThirdStepPublish:"May 30th 2022",dateEndFourthStepPublish:"August 18th 2022",dateEndFifthStepPublish:"October 17th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"5 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. H. Brian Sun is a surgeon, professor, and instructor in oral and maxillofacial surgery, and a researcher with multiple chapters, textbooks, and numerous article publications. He is a Clinical Assistant Professor at the Western University of Health Sciences, and a graduate alumnus of the UCLA Center for Oral/Head & Neck Oncology Research.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"184302",title:"Dr.",name:"H. Brian",middleName:null,surname:"Sun",slug:"h.-brian-sun",fullName:"H. Brian Sun",profilePictureURL:"https://mts.intechopen.com/storage/users/184302/images/system/184302.png",biography:"H. Brian Sun, DMD, MS is an oral and maxillofacial surgeon, a Clinical Assistant Professor at the Western University of Health Sciences, a Clinical Instructor at the University of Pacific, and a graduate alumnus of the UCLA Center for Oral/Head & Neck Oncology Research. His areas of interest include dentoalveolar surgery, orthognathic surgery, sleep surgery, trauma, pathology, and anesthesiology with a multitude of journal, textbook, and reference book authorships. He is a lifelong clinician, researcher, and educator with interests not only in the clinical but the scientific aspects of surgery who remains comfortable with both teaching and researching maxillofacial biology.",institutionString:"University of the Pacific",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of the Pacific",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,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:"455410",firstName:"Dajana",lastName:"Jusic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/455410/images/20500_n.jpeg",email:"dajana.j@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"9790",title:"Surgical Management of Head and Neck Pathologies",subtitle:null,isOpenForSubmission:!1,hash:"8ae195fe1164fd55b69b775d596f1e8a",slug:"surgical-management-of-head-and-neck-pathologies",bookSignature:"Ho-Hyun (Brian) Sun",coverURL:"https://cdn.intechopen.com/books/images_new/9790.jpg",editedByType:"Edited by",editors:[{id:"184302",title:"Dr.",name:"H. Brian",surname:"Sun",slug:"h.-brian-sun",fullName:"H. Brian Sun"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9500",title:"Recent Advances in Bone Tumours and Osteoarthritis",subtitle:null,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",slug:"recent-advances-in-bone-tumours-and-osteoarthritis",bookSignature:"Hiran Amarasekera",coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",editedByType:"Edited by",editors:[{id:"67634",title:"Dr.",name:"Hiran",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"17703",title:"Are Education and Experience Equally Remunerated across Employment Statuses? An Instrumental Variable Approach for Panel Data",doi:"10.5772/21316",slug:"are-education-and-experience-equally-remunerated-across-employment-statuses-an-instrumental-variabl1",body:'\n\t\tEstimating the returns to education and experience has been a topic for labour economists for decades, with a significant volume of research being devoted to appraising the causal effect of schooling on earnings. One central interest when estimating these returns has been to study whether differences exist across several demographic sectors; essentially, distinguishing between males and females, whites and non-whites, or natives and immigrants, to assess the possibility of wage discrimination, and to compute the extent of the wage gap between the groups (Harmon et al., 2003).
\n\t\t\tA rapidly growing literature examines differences in the return to education, distinguishing between the self-employed and wage earners (\n\t\t\t\t\tEvans & Leighton, 1989\n\t\t\t\t; Hamilton, 2000; Lazear & Moore, 1984; Rees & Shah, 1986). Fundamentally, these studies have set out not only to investigate earning differentials between the two employment groups
In this chapter, we set out to estimate the returns to education and to experience for both the self-employed and wage earners, with our aim being to address some of the issues raised above. In doing so, we provide evidence of such returns for three EU countries, namely Germany, Italy and the UK, using panel data information. Examining cross-country data is helpful in identifying common features that are not considered in a single-country analysis. Moreover, these countries cover a wide range of variation across Europe. Germany represents those countries with self-employment rates well below the EU average; Italy is an example of those Southern and peripheral countries with self-employment rates over 20%, and the UK stands for those countries exhibiting the average. Table 1 shows the 20-year evolution of the self-employment rate within the EU-15.
\n\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t10.8 | \n\t\t\t\t\t\t10.5 | \n\t\t\t\t\t\t14.4 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t15.3 | \n\t\t\t\t\t\t15.4 | \n\t\t\t\t\t\t13.6 | \n\t\t\t\t\t\t12.8 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t9.2 | \n\t\t\t\t\t\t8.4 | \n\t\t\t\t\t\t8.0 | \n\t\t\t\t\t\t8.9 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t14.3 | \n\t\t\t\t\t\t12.6 | \n\t\t\t\t\t\t12.6 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t12.7 | \n\t\t\t\t\t\t11.6 | \n\t\t\t\t\t\t10.0 | \n\t\t\t\t\t\t9.0 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t9.1 | \n\t\t\t\t\t\t9.4 | \n\t\t\t\t\t\t9.7 | \n\t\t\t\t\t\t12.0 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t35.4 | \n\t\t\t\t\t\t33.8 | \n\t\t\t\t\t\t31.3 | \n\t\t\t\t\t\t35.9 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t21.8 | \n\t\t\t\t\t\t20.8 | \n\t\t\t\t\t\t16.5 | \n\t\t\t\t\t\t16.8 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t24.4 | \n\t\t\t\t\t\t24.5 | \n\t\t\t\t\t\t23.6 | \n\t\t\t\t\t\t26.4 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t9.2 | \n\t\t\t\t\t\t10.0 | \n\t\t\t\t\t\t8.7 | \n\t\t\t\t\t\t6.1 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t10.1 | \n\t\t\t\t\t\t11.5 | \n\t\t\t\t\t\t10.0 | \n\t\t\t\t\t\t12.4 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t27.2 | \n\t\t\t\t\t\t25.8 | \n\t\t\t\t\t\t20.2 | \n\t\t\t\t\t\t24.2 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t23.5 | \n\t\t\t\t\t\t21.8 | \n\t\t\t\t\t\t18.0 | \n\t\t\t\t\t\t17.7 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t- | \n\t\t\t\t\t\t11.3 | \n\t\t\t\t\t\t9.8 | \n\t\t\t\t\t\t10.6 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t12.5 | \n\t\t\t\t\t\t13.0 | \n\t\t\t\t\t\t10.9 | \n\t\t\t\t\t\t13.8 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t15.9 | \n\t\t\t\t\t\t15.0 | \n\t\t\t\t\t\t13.6 | \n\t\t\t\t\t\t15.6 | \n\t\t\t\t\t
Self-employment rates (Eurostat Labour Force Survey). Note: Percentage of self-employed persons over total employed.
Using a homogeneous database, we investigate whether differences exist in the profitability of schooling and experience, both between the two employment statuses, and across the three sample countries. The database used in this work has been obtained from the European Community Household Panel (ECHP), from 1994 to 2000, which provides abundant information about the personal and labour characteristics of individuals, and has the advantage that this information is homogeneous across the sample countries, given that the questionnaire is the same and the collection process is coordinated by the Statistical Office of the European Community (EUROSTAT). Additionally, the application of panel data techniques offers some clear advantages over the traditional cross-sectional approaches. First, individual unobserved heterogeneity is controlled for. Second, biases arising from aggregation, selectivity, measurement error, and endogeneity can be dealt with in an appropriate form. Third, dynamic behavior, such as the movements into and out of self-employment, may be explicitly accounted for.
\n\t\t\tThe two usual estimators used in panel data, that is to say fixed and random effects, are, however, inadequate in this setting if the objective is to obtain consistent and efficient measures of the profitability of education and experience. Thus, the presence of time-invariant and possibly endogenous regressors (e.g. education), would make it impossible to estimate their associated parameters when a time or mean-differencing approach, i.e. the fixed effects, is applied. Additionally, the probable correlation between these time-invariant regressors and the unobserved effects causes the random effects estimator to be inconsistent. Altogether, this points to the advisability of using a hybrid technique that lies between both extremes. Moreover, the potential existence of measurement errors and/or endogeneity requires instrumental variables (IV) to obtain consistent estimates of the coefficients. As a consequence, the Hausman & Taylor (1981) estimator is the most adequate, since it has been shown to be an Efficient Generalised Instrumental Variable (EGIV). This procedure allows simultaneous control for the correlation between regressors and unobserved individual effects (as fixed effects) and to identify the estimates for the time-invariant covariates, such as education, as a random effects estimator. Furthermore, it eliminates the uncertainty associated with the choice of instruments, since exogenous included variables, and their means over time, are used as efficient instruments.
\n\t\t\tOur results show that returns to education are greater for workers in paid work, with non-linearities in the relationship between wages and educational levels (the so-called sheepskin effect). Both findings point to the relevance of signalling in the earnings of workers. Earnings experience profiles are, however, not very different across groups, especially when experience is not very great, indicating absence of delays in remuneration for workers.
\n\t\t\tThe rest of the chapter is structured as follows. In the next section, we consider the theoretical aspects of the returns to education and experience. Section 3 is devoted to the empirical model and to a discussion of the estimation procedure, the EGIV technique proposed in Hausman and Taylor (1981). Section 4 describes the data in the sample countries. Section 5 offers the estimates of the rates of return and examines the differences across countries to cast some light on labour-status differences. Finally, Section 6 provides a summary of the main results.
\n\t\tA new-born child enjoys an initial endowment of human capital (a conglomerate of intelligence, ability, motivation, characteristics of the social and economic environment, etc.) that can be improved upon by knowledge accumulation, both during the schooling period and through on-the-job experience. According to the human capital theory (Becker, 1962, 1964), there exists a positive relationship between investment in human capital and earnings, in such a way that a greater accumulation of human capital is rewarded in the labor market with higher earnings.
\n\t\t\tThe individual chooses to stay in school until the expected marginal benefit equals the expected marginal costs of one additional year of schooling, and differences in ability among individuals cause schooling choices to also differ. Empirically, a linear relationship is usually assumed between the log of the earnings and the set of regressors. This implies that ability influences only the intercept of log-earnings. Following this reasoning, we apply the widely-used wage equation (Mincer, 1974) that can be expressed as:
\n\t\t\twhere
Although specification (1) has been derived on the grounds of human capital theory, competing perspectives may generate similar conclusions. In particular, the sorting or signaling model also predicts that higher earnings are positively related to higher educational attainments. However, in this case, greater human capital does not lead to higher productivity (and thus, higher earnings), but greater human capital is acquired in order to signal higher productivity (Spence, 1973; Stiglitz, 1975). In other words, firms do not reward productivity in a direct way because this is not observed
As a consequence, estimating equation (1) does not help to discriminate between human capital and the sorting models; while it may be viewed as a good approach to assessing the effect of schooling on earnings, it is not completely satisfactory in elucidating which view prevails in the process of wage determination (Weiss, 1995). However, considering the self-employed as a control group may serve as a device to investigate the question, since signaling and screening purposes seem to be unimportant for this group of workers (Riley, 1979; Wolpin, 1977). The null hypothesis adopted by these authors is that returns to education will be higher in those occupations that exhibit signaling, on the basis that it is difficult to reconcile the idea that education for the self-employed could act as a sorting mechanism. As a consequence, returns to schooling for those in paid employment should be higher, since those individuals benefit from the dual effect of education: the productive and the informative functions. By contrast, the self-employed are only remunerated for the productive nature of education and, thus, returns are lower.
\n\t\t\tHowever, although the theoretical implications seem quite clear-cut, the empirical evidence is not conclusive. Focusing on the US, some authors report that self-employed earnings are less responsive to human capital variables than wage-employed earnings (Hamilton, 2000), thereby favouring the sorting hypothesis., whereas others (\n\t\t\t\t\tEvans and Jovanovic, 1989\n\t\t\t\t; \n\t\t\t\t\tEvans and Leighton, 1989\n\t\t\t\t; Kawaguchi, 2003) find that self-employed earnings equations have larger schooling coefficients than those corresponding to the wage-employed, rejecting the sorting hypothesis.
\n\t\t\tDistinguishing between self-employed and wage-earner returns may also be helpful in providing insights into the features of theoretical labour market models. Thus, studying the experience profile in earnings may serve to ascertain whether agency issues, learning and matching models, or compensating differentials theory, for example, better fit the labour market. A number of studies predict that earnings-experience profiles are flatter for the self-employed. Under the agency or risk theories (Lazear, 1981; Lazear & Moore, 1984), employers should pay less than the marginal productivity to workers when they are young, and more when they grow older, to avoid shirking on the job, contrary to the case of the self-employed, given that these individuals have no incentive to shirk. Similarly, asymmetric information models (Salop & Salop, 1976) argue that, because employers are interested in minimizing the quits of more productive workers, they offer tilted-up wage profiles as a screening device, in such a way that only workers with low probabilities of quitting apply for jobs. By contrast, since the self-employed are not willing to quit, they have flatter earnings profiles than those of wage earners. In the same vein, learning models claim that, due to sector-specific abilities that are unknown for the individual, workers may not match themselves to the appropriate sector. Those who realize they have a poor match quit their jobs, and only those with relatively good matches stay. This situation causes experience profiles to increase over time (Jovanovic, 1979, 1982). Furthermore, since the self-employed habitually invest strongly at the start-up of their businesses, they are not able to move out of their poor match, and therefore their experience profiles are flatter (Dunn & Holt-Eakin, 2000). All of these studies suggest steeper experience profiles for wage earners, especially at the very end of the years of experience distribution, to ensure long seniority in the firm.
\n\t\t\tContrary results, however, are found in the investment model, for example, which validates the claim that the self-employed obtain steeper earnings profiles because physical and human capital investments are not shared with an employer (Hashimoto, 1981). Similarly, steeper earning profiles of the self-employed can be observed in the cases where average returns to experience are distorted by the existence of a few, but very successful, entrepreneurs (the so-called “superstars”), whereas the bulk of the self-employed remain with low returns or leave for paid employment (Rosen, 1981).
\n\t\t\tIn summary, undisputed conclusions about the magnitude of the returns to education and experience for the self-employed and for salaried employees have not been achieved. The majority of prior analyses have focused on investigating only one country, without offering any kind of comparative study. Furthermore, only a limited number of articles have used data for a period of more than one year. Even when they have done so, they have estimated returns by pooling the data, an approach which does not allow for control for the unobserved characteristics of the individuals, nor for movements into or out of self-employment. Additionally, only the recent availability of panel data and the development of new statistical packages have permitted the application of EGIV techniques in order to gain efficiency in estimations. The aim of this chapter is precisely to address some of these gaps in the literature by computing returns to education and experience for a set of EU countries, using information provided in panel data form, which are statistically efficient.
\n\t\tThis section focuses on the empirical specification of the earnings equation and the methodology used for its estimation. The first sub-section is devoted to determining the most appropriate empirical model for our study, while the second describes the logic supporting the use of the Hausman-Taylor procedure in the estimation.
\n\t\t\tAs discussed in Section 2, estimates of the returns to education and experience for the self-employed and wage earners are usually obtained from Mincer-type wage regressions. Dating from the mid 20th century, a body of empirical work has investigated these returns across countries on the basis of such a specification (Psacharapoulos, 1973, 1981, 1985, 1994; Trostel et al., 2002). Cross-sectional information has normally been used, with the IV approach, progressively substituting for the traditional OLS estimation to account for endogeneity and ability biases, as well as measurement errors. This has resulted in estimates of the rates of return well above those obtained from OLS (Card, 1999, 2001).
\n\t\t\t\tOur estimated model is an extended version of the Mincerian-baseline equation (1), in which earnings rewarding more education can be seen as the combined effect of human capital accumulation and the effect of being identified as a graduate rather than as a dropout. It takes the following form:
\n\t\t\t\twhere
Rather than using the education measure normally employed in the literature, years of schooling, we consider the educational attainment of each worker, providing two clear advantages. First, it does not impose the annual marginal effect of schooling as being the same in each year of education, and second, the level of education is a more appropriate measure, since multiple education streams characterize European countries, and salary profiles used to be largely linked to the education category attained. In other words, they capture the possibility that credentials matter more than years of schooling
Educational attainment, which is considered time-invariant in our sample, represents the last completed level of schooling, classified as primary, secondary, and high. Primary includes elementary and below elementary school, secondary includes vocational and middle school, and tertiary or high includes university studies (in either short or long cycles). Consequently, the fragment “
The dependent variable is the natural log of net earnings, where these are defined as gross earnings less tax, expressed in per hour real terms. The earnings-experience profiles are analyzed by considering the number of years that an individual has been working, and its squared value divided by 100 to take care of the decreasing returns. Specifically, experience is measured as the difference between the current age and the age of initiation at work, thereby expressing potential experience. The remaining independent variables, represented in equation (3) by
The general model in (3) assumes that the error term uit consists of the sum of two components, i.e.
However, the presence of measurement errors and unobserved variables, such as ability, motivation, etc., that may be correlated with schooling, bias GLS estimates. Specifically, it has been shown that measurement errors bias downwards the GLS estimates (Angrist and Krueger, 1999) although recent evidence (Card, 2001) only attributes a 10% gap, at most, to this source of bias. By contrast, since schooling and any unobserved ability may be positively correlated, omitting measures of ability results in the schooling coefficient being biased upwards (Griliches, 1977). Consequently, some effort must be made to alleviate such an ability bias as much as possible. When a direct indication of ability, such as IQ score tests, or information from twins or siblings, is not available (see Ashenfelter & Krueger, 1994, and Miller et al., 1995), the most appropriate exercise is to select an instrumental variables estimator, through which schooling is instrumented with variables that are correlated with it, but not with errors. A broad range of instruments have been proposed in the literature. Typical examples are those known as natural experiments (see Rosenzweig and Wolpin, 2000, for a summary) which include: i) school reforms and features of the school system (Harmon and Walker, 1995); ii) the proximity to College of the place of residence (Card, 1995); iii) other supply-side instruments capturing features of the education system (see Card, 2001 for a survey of the literature); and iv) the season of birth of the individual (Angrist and Krueger, 1991).
\n\t\t\t\tWhen using IV in cross-sections, a common finding is that estimates are 20% higher, or even more, than OLS estimates. This is a rather unexpected result, since OLS is already believed to provide upward-biased estimates arising from the ability bias. Some reasons have been proposed to explain such a result. Apart from the positive publication bias (Ashenfelter et al., 1999), IV estimates may be biased upwards further than OLS due to the existence of unobserved differences between the characteristics of the treatment and comparison groups implicit in the IV scheme (Bound et al., 1995). Specifically, when treatment effects are used, since returns to education are heterogeneous across individuals, the IV estimates tend to recover the returns to education of the population group most affected by the intervention, so that IV estimates are then a better approximation for the returns to education of the affected group, rather than for the whole population (Card, 1999, 2001). Similarly, IV estimates will tend to be biased towards the returns to schooling attainments that are most common in the sample data (see Belzil and Hansen, 2002).
\n\t\t\t\tBoth the available data structure and the existence of problems associated with the choice of instruments have influenced the procedure applied in this study. On the one hand, the ECHP is in panel data form, but does not provide information on IQ tests, and the presence of twins is not especially accounted for. On the other hand, although the number of alternative instruments routinely considered in the literature is sufficiently wide, their application to our data is quite complex. This has led us to consider an alternative procedure for estimation, in which the availability of panel data is taken into account, namely the IV-type model proposed by Hausman and Taylor (1981). Our selection of this procedure is motivated by several considerations. As is well known, the availability of panel data allows us to control for individual unobserved heterogeneity (possibly correlated with other included variables), since this factor may be eliminated by mean or time-differencing, i.e. by applying a fixed effects-type estimator (Polachek & Kim, 1994). Although this within estimator is probably not fully-efficient, it produces consistent estimates. However, when operating in this way, coefficients of the time-constant variables (e.g. the level of education) cannot be estimated, since they disappear when mean or time-differences are constructed. For its part, a pure random effects estimator, the GLS, produces biased and inconsistent estimates, assuming as it does that there is no correlation between any of the regressors and the individual effects. In our case, the GLS estimator is not valid because education and experience may be correlated with individual effects.
\n\t\t\t\tOne way to obtain consistent estimates of the returns to education and experience would be to find instruments for these variables which are potentially correlated with the individual effects. The choice of the appropriate instruments is, however, not an easy task, since the use of instruments that are weakly correlated with endogenous variables may produce downward-biased estimates, even with large samples (see Bound et al, 1995; Chamberlain & Imbens, 2004; Staiger & Stock, 1997), generating uncertainty in the selection of instruments. Consequently, what we require is a procedure that controls for the endogeneity of education (and possibly other variables), but which is still able to recover the coefficient of time-invariant regressors. Hausman & Taylor (1981) propose a model where some of the regressors may be correlated with individual effects, as opposed to the random effects model, where no regressor can be correlated with the individual effect, and to the fixed effects model, where all the regressors may be correlated with individual effects. If, in addition, this procedure does not require instruments excluded in the regression but the instruments used are precisely those included in the wage regression, the Hausman-Taylor estimator is, potentially, the best choice.
\n\t\t\t\tThis Hausman-Taylor estimator is an instrumental variables estimator that uses both the between and within variations of the strictly exogenous variables as instruments. More specifically, the individual means of the strictly exogenous regressors are used as instruments for the time invariant regressors correlated with individual effects. This procedure is implemented in the following steps. First, equation (3) is estimated by pooled Two Stages Least Squares (2SLS), where the set of variables mentioned above act as instruments. Second, the pooled 2SLS residuals are used to obtain estimates of
Formally, the Hausman-Taylor model can be represented in its most general form as follows:
\n\t\t\t\twhere
In the case under consideration, education is a potentially endogenous, time-invariant regressor, whereas the experience variables may also be endogenous, but time-varying. Since we are interested in the coefficients of these variables, all the exogenous variables (either time-invariant or time-varying), plus the individual means over time of all the time-varying regressors can be used as instruments to obtain consistent estimates of the returns to education and experience. These instruments are chosen based on Hausman specification tests (Hausman, 1978) in a sequential procedure according to (Baltagi et al., 2003). Specifically, a first Hausman test is the standard to distinguish between the random and fixed effects estimators. A second Hausman test contrasts the Hausman-Taylor against the fixed effects model. Although the fixed effects estimator is not an option in our study, since it does not allow for the estimation of the coefficients of the time invariant regressors, it is useful in order to test the strict exogeneity of the regressors used as instruments in the Hausman-Taylor estimation. Thus, when strict exogeneity for a set of regressors is rejected, others must be considered in the estimation to act as instruments. Once the second Hausman test has identified the regressors that are strictly exogenous, they are used as instruments in the Hausman-Taylor estimation. Additionally, the variance-covariance structure can be taken into account to obtain more efficient estimators (Im et al., 1999), so that the Hausman-Taylor procedure is a good alternative to pure IV estimation when panel data is available.
\n\t\t\tThe data used in this study come from the ECHP for the period 1994-2000. As stated earlier, this is the only database that provides individual information that is comparable for all EU countries, since the design and organization of the survey is coordinated by EUROSTAT. Individual or micro data is preferred to more aggregate data, both because they provide more flexibility in creating sample restrictions, and because they allow us to directly control for individual-level characteristics in our regression.
\n\t\t\tAt the time of the interview, individuals are requested to indicate whether they are working in a job for at least 15 hours a week. If so, workers identify themselves as either self-employed or employed when asked about their main labor market activity (paid apprenticeships and unpaid work in a family enterprise are excluded from the analysis). As a consequence, the job status of a particular worker may vary from year to year. In the sample, we have selected those workers, either self-employed or wage earners, who have provided information for all variables under consideration. These variables include personal and labor characteristics such as gender, marital status, schooling, experience, earnings, seniority, occupation, whether the individual works in the private or in the public sector, the number of hours worked per week, and if the worker has taken some training course during the last year.
\n\t\t\t\n\t\t\t\tTable 2 illustrates the main characteristics of our samples for the three countries. The number corresponding to wage earners in the sample ranges from about 6,500 in the UK to more than 8,000 in Germany. For the self-employed, the figures are considerably lower, varying between less than 1,000 in Germany to almost 2,500 in Italy. Sample proportions are not very different from population rates (see Table 1). Bearing in mind that self-employed earnings are commonly believed to be under-reported (Hamilton, 2000), wage earners appear to earn a little more than the self-employed in Italy, whereas the opposite occurs in Germany and in the UK. Note that dispersion in earnings is higher for the self-employed, reflecting a greater heterogeneity in these types of activities, from low-ability jobs (retailers and basic services) to those of professionals, such as doctors or lawyers. People living in Germany and in the UK obtain higher earnings than those residing in Italy.
\n\t\t\tThe years of experience are clearly higher in the self-employed sector than in that of wage earners. The majority of individuals in Italy present low educational levels, the percentage being somewhat higher among the self-employed. By contrast, in Germany, workers in general are highly educated, with more than 40% of the self-employed having attained a tertiary degree. The case of the UK is especially appealing since workers attaining a secondary level are clearly fewer than those of primary or higher education, indicating some kind of a bi-modal distribution. Roughly speaking, where self-employment rates are higher, the self-employed themselves are less educated, as against countries with low self-employment rates, which exhibit a higher proportion of workers, either wage earners or the self-employed, who have obtained at least a secondary level of education.
\n\t\t\t\n\t\t\t\t\t\t | \n\t\t\t\t\t\t | \n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t9.06 (8.26) | \n\t\t\t\t\t\t22.94 (10.98) | \n\t\t\t\t\t\t12.31 | \n\t\t\t\t\t\t46.19 | \n\t\t\t\t\t\t41.50 | \n\t\t\t\t\t\t840 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t8.48 (4.30) | \n\t\t\t\t\t\t20.48 (11.16) | \n\t\t\t\t\t\t19.48 | \n\t\t\t\t\t\t57.88 | \n\t\t\t\t\t\t22.64 | \n\t\t\t\t\t\t8066 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t6.21 (5.31) | \n\t\t\t\t\t\t23.69 (13.34) | \n\t\t\t\t\t\t56.82 | \n\t\t\t\t\t\t31.95 | \n\t\t\t\t\t\t11.23 | \n\t\t\t\t\t\t2494 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t6.73 (3.55) | \n\t\t\t\t\t\t18.03 (11.07) | \n\t\t\t\t\t\t44.13 | \n\t\t\t\t\t\t44.63 | \n\t\t\t\t\t\t11.24 | \n\t\t\t\t\t\t7865 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t8.71 (9.73) | \n\t\t\t\t\t\t25.33 (13.03) | \n\t\t\t\t\t\t46.48 | \n\t\t\t\t\t\t13.74 | \n\t\t\t\t\t\t39.78 | \n\t\t\t\t\t\t1053 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t7.88 (5.59) | \n\t\t\t\t\t\t20.02 (12.86) | \n\t\t\t\t\t\t45.99 | \n\t\t\t\t\t\t13.70 | \n\t\t\t\t\t\t40.31 | \n\t\t\t\t\t\t6433 | \n\t\t\t\t\t
Sample averages (ECHP 1994-2000). Note: Standard errors between parentheses. Earnings are expressed in terms of the PPP. Observations per year is the average, since figures vary from year to year.
This section presents the empirical evidence which is then assessed in the light of the aspects mentioned in Section 2, with the aim of providing some insights into the functioning of the European labour markets. The results from EGIV Hausman-Taylor estimations are shown in Table 3, along with the tests for choosing the appropriate instruments (Baltagi et al., 2003). In column H1, a standard Hausman test rejects the random effects hypotheses in favour of the fixed effect estimator. A second Hausman test contrasting the Hausman-Taylor against the fixed effects model (column H2), is useful in order to test the strict exogeneity of the regressors used as instruments in the Hausman-Taylor estimation. Once this second Hausman test has identified which regressors are strictly exogenous, they are then used as instruments in the Hausman-Taylor estimation.
\n\t\t\tComparing the coefficients of Table 3 with those from the GLS estimation (not shown, but available from the authors upon request), we can note that the Hausman-Taylor estimation provides coefficients of education and experience that, in general, are consistently much higher. This is in accordance with the typical finding reported in the literature when using instrumental variables of upward bias in IV-type, compared to OLS-type estimations.
\n\t\t\tRegarding the returns to education, wages increase with educational attainment, with returns higher among wage earners in Germany and Italy and quite similar in the UK, and the coefficients for the self-employed with secondary education level in Germany and the UK are non-significant. The percentage changes across educational categories, computed as the difference in the percentage change in wage for group i relative to the group i-1, eβi- eβi-1, where βi is the coefficient for the dummy variable for group I, show that returns increase as we move up the qualification ladder, especially from secondary to higher education, which supports a convex configuration of earnings on the returns to education, thus confirming the importance of the sheepskin effect. Both results, higher returns to education for paid workers, and increasing non-linearities in the relationship between wages and educational attainment, indicate some degree of a sorting or signalling role played by education.
\n\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t0.053** (3.72) | \n\t\t\t\t\t\t-0.068** (-2.83) | \n\t\t\t\t\t\t0.654 (0.89) | \n\t\t\t\t\t\t1.243* (2.45) | \n\t\t\t\t\t\t234.96 (0.0000) | \n\t\t\t\t\t\t8.44 (0.9986) | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earners | \n\t\t\t\t\t\t0.065** (22.24) | \n\t\t\t\t\t\t-0.084** (-22.21) | \n\t\t\t\t\t\t0.848** (8.83) | \n\t\t\t\t\t\t1.291** (17.31) | \n\t\t\t\t\t\t1117.89 (0.0000) | \n\t\t\t\t\t\t10.51 (0.9921) | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t0.037** (6.30) | \n\t\t\t\t\t\t-0.053** (-4.66) | \n\t\t\t\t\t\t0.339** (2.78) | \n\t\t\t\t\t\t0.631** (6.35) | \n\t\t\t\t\t\t138.47 (0.0000) | \n\t\t\t\t\t\t34.66 (0.0946) | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earners | \n\t\t\t\t\t\t0.047** (27.52) | \n\t\t\t\t\t\t-0.089** (-23.60) | \n\t\t\t\t\t\t0.551** (15.09) | \n\t\t\t\t\t\t0.847** (19.07) | \n\t\t\t\t\t\t2103.26 (0.0000) | \n\t\t\t\t\t\t49.63 (0.0752) | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t0.053** (5.16) | \n\t\t\t\t\t\t-0.055** (-3.41) | \n\t\t\t\t\t\t0.629 (0.74) | \n\t\t\t\t\t\t0.714** (3.54) | \n\t\t\t\t\t\t275.90 (0.0000) | \n\t\t\t\t\t\t5.92 (0.9999) | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earners | \n\t\t\t\t\t\t0.063** (27.27) | \n\t\t\t\t\t\t-0.106** (-27.28) | \n\t\t\t\t\t\t0.524** (3.41) | \n\t\t\t\t\t\t0.706** (15.14) | \n\t\t\t\t\t\t2064.11 (0.0000) | \n\t\t\t\t\t\t4.58 (1.0000) | \n\t\t\t\t\t
Estimated Coefficients of Mincerian Earnings Function by Hausman-Taylor. Notes: t-ratios between parentheses (p-values in H1 and H2). Both panels are unbalanced, since the employment status may vary across individuals over time. Controls used. Gender: 1 for male and 0 for female. Marital status: married, single, divorced, widow or separated. Training: if the worker has realized some course of occupational training. Eight dummies that indicate occupation. A dummy indicating whether the individual works in the private or the public sector. Dummies that indicate seniority: less than two years, between 2 and 10 years, and more than 10 years. Dummies that indicate the year. * Significant at the 5% level. ** Significant at the 1% level. H1 tests the random effects estimator against the fixed effects. H2 tests the Hausman-Taylor estimator against the fixed effects.
Across countries, experience increases human capital accumulation during the life cycle. At first sight, returns to experience are greater for wage earners, even though they depreciate at a faster rate than in the case of the self-employed. In order to extract more robust conclusions, a series of indicators are used. First, the maximum return, i.e. the point where experience ceases to add positively to earnings, which is defined by ∂lnw/∂Exp from earnings equation (3), that is to say, the number of years that equals μ1+μ2 Exp/50 to 0 provided μ2<0. The third column in Table 4 is viewed as always being greater for the self-employed, but with marked differences across countries. Thus, the maximum number of years is almost equal in Germany, close to 39 years, with differences around ten years in Italy and almost 20 in the UK. In this latter case, experience is continually adding to earnings during the whole working life of the self-employed. The effects of experience are less long-lasting in Italy, especially among wage earners.
\n\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t39 | \n\t\t\t\t\t\t2,18 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t38,7 | \n\t\t\t\t\t\t2,36 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t35 | \n\t\t\t\t\t\t1,61 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t26 | \n\t\t\t\t\t\t1,49 | \n\t\t\t\t\t
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\tSelf-employed | \n\t\t\t\t\t\t48 | \n\t\t\t\t\t\t2,51 | \n\t\t\t\t\t
\n\t\t\t\t\t\t | Wage earner | \n\t\t\t\t\t\t30 | \n\t\t\t\t\t\t2,06 | \n\t\t\t\t\t
Returns to experience. Note: Own calculations from the estimated coefficients obtained in Tables 3.
We have computed the series of rates of return as μ1+μ2 Exp/50, with “Exp” playing the role of a variable. Column 4 in Table 4 reports the rate of return evaluated at the sample average in each country. Values are quite similar in Germany and the UK, and clearly lower in Italy. The greatest difference between the self-employed and wage earners is found in the UK, close to 0.5.
\n\t\t\tEarnings-experience profiles are constructed from the series of rates of return to experience. Figure 1 displays these profiles for both types of workers in the sample countries. It is clear from the evidence that the profiles are very similar during the first years, (14 in Italy, around 20 in the UK and almost 38 in Germany), with the profiles being slightly steeper for wage earners; then the profiles switch position, revealing the long-lasting effects of experience for the self-employed.
\n\t\t\tOverall, the body of evidence seems to indicate that investment considerations may be at work, al least in the long run. This can be due to the fact that returns to other capital accumulation, physical or technological, are more long-lasting than those from human capital alone. Alternatively, it can be argued that, if mobility costs are reduced, only well-matched self-employed workers remain as such, with less successful entrepreneurs leaving self-employment and undertaking paid employment. Taken together, it may be reasoned that competitive functioning of the labour market may be at work in these countries. While the different theories cannot be compared one with another in the absence of a more detailed analysis, it nevertheless appears that imperfections in the labour market play a less important role than expected.
\n\t\t\tIn summary, as regards the functioning of the labour market in the set of EU countries considered in this Chapter, two basic ideas emerge. First, returns to education are, in
\n\t\t\tEarnings experience profiles for the three sample countries
general, found to be higher for wage earners, which can be interpreted as an indication of the relevance of the signalling role of education in determining earnings. This latter result was expected, bearing in mind the prevalent wage rates in the EU countries, where earnings are usually linked to the education level attained by the worker. Second, according to the evidence shown by the earning-experience profiles, which tend to be steeper in the case of the self-employed, traits of competitiveness can be discerned, with little or no evidence of imperfections.
\n\t\tThe aim of this Chapter has been to extend the existing research on the returns to human capital accumulation that differentiates between the self-employed and wage earners. This has been carried out by providing evidence in a cross-country framework using a homogenous database, which mitigates the problems associated with the existence of different data sources across countries, by using a panel data approach that is useful in dealing with endogeneity and selectivity biases, as well as unobserved heterogeneity, and by applying an efficient estimation method that allows for the correlation between individual effects and time-invariant regressors, and that avoids the insecurity associated with the choice of the appropriate instruments.
\n\t\t\tInformation from the ECHP for the period 1994-2000 has been used, allowing us to apply an Efficient Generalised Instrumental Variable estimator that provides consistent estimates of the rates of return to education and experience. Education has been represented by dummies of qualification levels (primary, secondary and higher), and experience has been measured as the difference between the current age and the age of initiation at work. The results have been presented in a reduced form, with the aim being to provide both comparisons across countries about the earnings differentials between the two employment statuses analyzed, and evidence as to whether such differences are consistent with the predictions offered by a variety of theoretical models.
\n\t\t\tThe self-employed have been used as a control group to help in assessing the true impact of credentials achieved in the process of wage determination, as well as in determining which type of theoretical structure underlies labour market behavior. We have operated under the premise that, on the basis that signalling is of much less importance for the self-employed, comparing across both types of employment statuses should show that, for the sorting hypothesis to be accepted, returns to education for wage earners are significantly higher than those for the self-employed, as well as possibly increasing in a non-linear way. Similarly, most labour market models based on imperfect information predict steeper experience-earnings profiles for wage earners, whereas competitive traits in the labor market would imply similar or flatter profiles for this category of worker.
\n\t\t\tThe evidence that emerges for the sample countries tends to support the view that signalling theory is indeed relevant in determining individual earnings, in that, first, returns to education are lower where signalling is expected to play a less important role, i.e. in the case of the self-employed, and, second, certain non-linearities appear. Furthermore, earnings-experience profiles are found to be steeper for the self-employed in the long-run, indicating a certain significance of competitiveness in the labour markets.
\n\t\t\tSome aspects of the investigation have been omitted or require further attention. We are conscious that selectivity issues should be carefully dealt with, when the development of a reliable instrument makes this possible (Semykina & Wooldridge, 2010). Furthermore, obtaining structural estimates for the returns to education and experience would probably require dynamic programming models of occupational choice (Belzil & Hansen, 2002). Finally, the availability of richer panel data sets is of particular importance to control for the movements into and out of self-employment. These topics are all matters for future research, and will undoubtedly be helpful in carrying out a more in-depth investigation into the behaviour of the labour market and wage determination in the EU countries, in such a way that we can more fully assess their degrees of competitiveness.
\n\t\tWe are grateful to Adriaan Kalwij for his useful comments and suggestions. We also wish to acknowledge the financial support provided by the Spanish Ministry of Science and Innovation, Project ECO2008-01297.
\n\t\tChronic myeloproliferative disorders are a group of clonal diseases of the stem cell. It is a group of several diseases with some common features. They derive from a multipotential hematopoietic stem cell. A clone of neoplastic cells in all these neoplams is characterized by a lower proliferative activity than that of acute myeloproliferative diseases. In each of these diseases, leukocytosis, thrombocythemia, and polyglobulia may appear at some stage, depending on the diagnosis [1, 2].
The research on interferon has been going on since the 1950s [3]. Then, the attention was paid to its influence on the immune system. It has been noted that it can exert an antiproliferative effect by stimulating cells of the immune system [4]. In 1987, a publication by Ludwig et al. was published, which reported the effectiveness of interferon alpha in the treatment of chronic myeloproliferative disorders [5].
More and more new studies have been showing the effectiveness of interferon alpha in reducing the number of platelets, reducing the need for phlebotomies in patients with polycythemia vera and also in reducing the number of leukocytes. Moreover, interferon reduced the symptoms of myeloproliferative disorders such as redness and itching of the skin. Additionally, it turned out to be effective in reducing the size of the spleen.
Further studies on the assessment of remission using molecular-level response assessments indicate that the interferon action in chronic myeloproliferation diseases targets cells from the mutant clone with no effect on normal bone marrow cells [6].
Over the years, interferon alpha-2a and interferon alpha-2b have been introduced into the treatment of chronic myeloproliferation, followed by their pegylated forms. The introduction of pegylated forms allowed for a reduction in the number of side effects and less frequent administration of the drug to patients. In recent years, monopegylated interferon alpha-2b has been used to further increase the interval between drug administrations while maintaining its antiproliferative efficacy.
The exact mechanism of action of interferon alpha in the treatment of chronic myeloproliferative disease is still not fully understood, but it has an impact on JAK2 (Janus Kinase) signal transducers and activates the STAT signal pathway (Janus Kinase/SignalTransducer and Activator of Transcription).
Interferon alpha binds to IFNAR1 and IFNAR2c, which are type I interferon receptors. Interferon alpha has an impact on JAK2(Janus Kinase) signal transducers and activates the STAT signal pathway. The disturbances in this signaling pathway are observed in chronic myeloproliferative disorders [7].
Interferon inhibits the JAK-STAT signaling pathway by directly inhibiting the action of thrombopoietin in this pathway [8].
So far, three driver mutations have been described in the course of chronic myeloproliferative diseases that affect the functioning of the JAK-STAT pathway.
JAK2 kinase and JAK1, JAK3, and TYK2 kinases belong to the family of non-receptor tyrosine kinases. They are involved in the intracellular signal transduction of the JAK-STAT pathway. It is a system of intracellular proteins used by growth factors and cytokines to express genes that regulate cell activation, proliferation, and differentiation. The mechanism of JAK activation is based on the autophosphorylation of tyrosine residues that occurs after ligand binds to the receptor. JAK2 kinase transmits signals from the hematopoietic cytokine receptors of the myeloid lineage (erythropoietin, granulocyte-colony stimulating factor thrombopoietin, and lymphoid lineage [9].
A somatic G/T point mutation in exon 14 of the JAK2 kinase gene converts valine to phenylalanine at position 617 (V617F) in the JAK2 pseudokinase domain, which allows constitutive, ligand-independent activation of the receptor to trigger a proliferative signal [10].
Mutation of the MPL gene, which encodes the receptor for thrombopoietin, increases the sensitivity of magekaryocytes to the action of thrombopoietin, which stimulates their proliferation [11].
Malfunction of calreticulin as a result of mutation of the CARL gene leads to the activation of the MPL-JAK/STAT signaling pathway, which is independent of the ligand, as calreticulin is responsible, for the proper formation of the MPL receptor. Consequently, there is a clonal proliferation of hematopoietic stem cells [12].
Below, we provide an overview of some clinical studies on the efficacy of interferon in chronic myeloproliferative disorders.
Polycythemia vera (PV) is characterized by an increase in the number of erythrocytes in the peripheral blood.
Polycythemia vera is caused by a clonal mutation in the multipotential hematopoietic stem cell of the bone marrow. The mutation leads to an uncontrolled proliferation of the mutated cell clone, independent of erythropoietin and other regulatory factors. As the mutation takes place at an early stage of hematopoiesis, an increase of the number of erythrocytes as well as of leukocytes and platelets is observed in the peripheral blood. The cause of proliferation in PV independent from external factors is a mutation in the Janus 2 (JAK2) tyrosine kinase gene. The V617F point mutation in the JAK2 gene is responsible for about 96% mutation, and in the remaining cases the mutation arises in exon 12. Both mutations lead to constitutive activation of the JAK-STAT signaling pathway [13].
As a result of the uncontrolled proliferation, blood viscosity increases, which generates symptoms such as headaches and dizziness, visual disturbances, or erythromelalgia. As the number of all hematopoietic cells, including the granulocytes ones, increases, the difficult to control symptoms of their hyperdegranulation may appear, among which gastric ulcer or skin itching is often observed. During the disease progression, the spleen and liver become enlarged.
The most common complication of the disease is episodes of thrombosis, especially arterial one. During the course of the disease, it can also evolve into myelofibrosis or acute myeloid leukemia.
The treatment of PV is aimed at preventing thromboembolic complications, relieving the general symptoms, the appearance of hepatosplenomegaly as well as preventing its progression.
Each patient should receive an antiplatelet drug chronically, and usually acetylsalicylic acid is the choice. Most often, the treatment is started with phlebotomy in order to rapidly lower the hematocrit level. If cytoreductive therapy is necessary, the drugs of first choice are hydroxycarbamide and interferon [2].
However, the research on the mechanism of the action of interferons is still ongoing. In vitro studies with CD34+ cells from peripheral blood of patients diagnosed with polycythemia vera showed that interferon inhibits clonal changed cells selectively. It was found that interferon alpha-2b and pegylated interferon alpha-2a reduce the percentage of cells with JAK2 V617F mutation by about 40%. Pegylated interferon alpha-2a works by activating mitogen-activated protein kinase P38. It affects CD34+ cells of patients with polycythemia vera by increasing the rate of their apoptosis [6].
A case of a patient with PV with a confirmed chromosomal translocation t(6;8) treated with interferon alpha-2b, which resulted in a reduction of the clone with translocation by 50% from the baseline value, was also described [14].
In 2019, the results of a phase II multicenter study were published, which aimed at assessing the effectiveness of recombinant pegylated interferon alpha-2a in cases of refractory to previously hydroxycarbamide therapy. The study included 65 patients with essential thrombocythemia (ET) and 50 patients with polycythemia vera. All patients had previously been treated with hydroxycarbamide and showed resistance to this drug or its intolerance.
The assessment of the response was performed after 12 months of treatment. Overall response rate to interferon was higher in patients diagnosed with ET than in patients with polycythemia vera. In essential thrombocythemia, the percentage of achieved complete remissions was 43 and 26% of partial remissions. The remission rate in ET patients was higher if calreticulin CALR gene mutation was present. Patients with polycythemia vera achieved complete remission in 22% of cases and partial remission in 38% of cases.
Treatment-related side effects that follow to discontinuation of treatment were reported in almost 14% of patients [15].
The duration of response to treatment with pegylated interferon alpha-2a and the assessment of its safety in long-term use in patients with chronic myeloproliferative disorders was the goal of a phase II of the single-center study. Forty-three adult patients with polycythemia vera and 40 patients with essential thrombocythemia were enrolled in the study. The complete hematological response was defined as a decrease in hemoglobin concentration below 15.0 g/l, without phlebotomies, a resolution of splenomegaly, and no thrombotic episodes in the case of PV, and for essential thrombocythemia—a decrease platelet count below 440,000/μl and two other conditions as above. The assessment of the hematological response was performed every 3–6 months. The median follow-up was 83 months.
The hematological response was obtained in 80% of cases for the entire group. In patients with polycythemia vera, 77% of patients achieved a complete response (CR) while 7% a partial response (PR). The duration of response averaged 65 months for CR and 35 months for PR. In the group of patients diagnosed with essential thrombocythemia, CR was achieved in 73% and PR in 3%. The durance of CR was 58 months and PR was 25 months.
The molecular response for the entire group was achieved in 63% of cases.
The overall analysis showed that the duration of hematological remission and its achievement with pegylated interferon alpha-2a treatment is not affected neither by baseline disease characteristics nor JAK2 allele burden and disease molecular status. There was also no effect on age, sex, or the presence of splenomegaly.
During the course of the study, 22% of patients discontinued the treatment, because of toxicity. Toxicity was the greatest at the beginning of treatment. The starting dose was 450 μg per week and was gradually tapered off.
Thus, on the basis of the above observations, the researchers established that pegylated interferon alpha-2a may give long-term hematological and molecular remissions [16].
The assessment of pegylated interferon alpha-2a in group of patients diagnosed with polycythemia vera only was performed. The evaluation was carried out on a group of 27 patients. Interferon decreased the JAK2 V617F allele burden in 89% of cases. In three patients who were JAK2 homozygous at baseline, after the interferon alpha-2a treatment wild-type of JAK2 reappeared. The reduction of the JAK2 allele burden was estimated from 49% to an average 27%, and additional in one patient the mutant JAK2 allele was not detectable after treatment. It can therefore be postulated that the action of pegylated interferon alpha-2a is directed to cells of the polycythemia vera clone [17].
In 2005, the results of treatment by pegylated interferon alpha-2b of 21 patients diagnosed with polycythemia vera and 21 patients diagnosed with essential thrombocythemia were published. In the case of polycythemia vera in 14 patients, PRV-1 gene mutation was initially detected. In 36% of cases, PRV-1 expression normalized after treatment with pegylated interferon alpha-2b. For the entire group of 42 patients, the remission assessment showed that complete remission was achieved in 69% cases after 6 months of treatment. However, only in 19 patients remission was still maintained 2 years after the start of the study. Pegylated interferon alpha-2b was equally effective in patients with PV and ET. The use and the type of prior therapy did not affect the achievement of remission [18].
Another study with enrolled only PV patients included 136 patients. They were divided into two arms. One group received interferon alpha-2b and the other group received hydroxycarbamide. Interferon dosage was administered in 3 million units three times a week for 2 years and then 5 million units two times a week. Hydroxycarbamide was administered at a dose between 15 and 20 mg/kg/day.
In the group of patients treated with interferon, a significantly lower percentage of patients developed erythromelalgia (9.4%) and distal parasthesia (14%) compared with the group treated with hydroxycarbamide, for whom these percentages were respectively: 29 and 37.5%. Interferon alpha-2b was found to be more effective in inducing a molecular response, which was achieved in 54.7% of cases, in comparison with hydroxycarbamide—19.4% of cases, despite the fact that the percentage of achieved general hematological responses did not differ between the groups and amounted about 70%. The 5-year progression free period in the interferon group was achieved in a higher percentage (66%) than in the hydroxycarbamide group (46.7%) [19].
The most recent form of interferon approved by the
Thanks to these changes to the structure of the molecule, it was possible to achieve a significant increase in its half-life. Ropeginterferon can be administered subcutaneously to patients every 14 days. The clinical trials conducted so far have assessed the ropeginterferon dose from 50 micrograms to a maximum dose of 500 microgams administered as standard every 2 weeks. The possible dose change in case of side effects includes not only the reduction of the drug dose itself, but also the extension of the interval between doses. The extension of the dosing interval up to 4 weeks was assessed.
Ropeginterforn was approved in 2019 by the EMA for the use in patients diagnosed with polycythemia vera without splenomegaly, as monotherapy.
Ropeginterferon, like the previous forms of interferons used in treatment, is contraindicated in patients with severe mental disorders, such as severe depression. It is also a contraindication in patients with noncompensatory standard treatment of disorders of the thyroid gland as well as severe forms of autoimmune diseases. The safety profile of ropeginterferon is similar to that of other forms of alpha interferons. The most common side effects are flu-like symptoms [20].
Ropeginterferon has been shown to exhibit in vitro activity against JAK2-mutant cells. The activity of ropeginterferon against JAK2-positive cells is similar to that of other forms of interferons used actually for standard therapy. Ropeginterferon has an inhibitory effect on erythroid progenitor cells with a mutant JAK2 gene. At the same time, it has almost no effect on progenitor cells without the mutated allele (JAK2-wile-type) and normal CD34+ cells. A gradual decrease of JAK2-positive cells was observed in patients with PV during ropeginterferon treatment. The examination was performed after 6 and 12 months of treatment. In comparison, the reduction in the percentage of JAK2 positive cells in patients treated with hydroxycarbamide was significantly lower.
These results may suggest that ropeginterferon may cause elimination of the mutant clone, but further prospective clinical trials are needed to confirm this theory. The evaluation was performed on a group of patients enrolled in the PROUD-PV study who were treated in France [21].
In 2017, a multicenter study was opened in Italy. The study was of the second phase. In total, 127 patients with polycythemia vera were included in the study. All patients enrolled on the study had low-risk PV. The clinical trial consisted of two arms. Patients received phlebotomies and low-dose aspirin in one arm and ropeginterferon in the other arm. The aim of the study was to achieve a hematocrit of 45% or lower without any evidence of disease progression. Ropeginterferon was administered every 2 weeks at a constant dose of 100 μg.
The response to the treatment was assessed after 12 months. The reduction of hematocrit to the assumed level was achieved in significantly higher percentage of patients in the ropeginterferon group than of patients who received only phlebotomies and aspirin. In addition, none of the patients treated with ropeginterferon experienced disease progression during the course of the study, while among those treated with phlebotomies, 8% of patients progressed.
Grade 4 or 5 adverse events were not observed in patients treated with ropeginterferon, and the incidence of remaining adverse event (AE) was small and comparable in both arms. The most common side effects in the ropeginterferon group were flu-like symptoms and neutropenia; however, the third-grade neutropenia was the most common (8% of cases) [22].
One of the most important clinical studies on the use of ropeginterferon was the PROUD-PV study and its continuation: the CONTINUATION-PV study. These were three-phase, multicenter studies. The aim of the study was to compare the effectiveness of ropeginterferon in relation to hydroxycarbamide. The study included adult patients diagnosed with polycythemia vera treated with hydroxycarbamide for less than 3 years and no cytoreductive treatment at all. In total, 257 patients received this treatment. The patients were divided into two groups: those receiving ropeginterferon or the other being given hydroxycarbamide.
During the PROUD-study, drug doses were increased until the hematocrit was achieved below 45% without the use of phlebotomies, and the normalization of the number of leukocytes and platelets was reached.
The PROUD-PV study lasted 12 months. After this time, the patients continued the treatment under the CONTINUATION-PV study for further 36 months. After the final analysis performed in the 12th month at the end of PROUD study, it was found that the hematological response rates did not differ between the ropeginterferon and hydroxycarbamide treatment groups. These were consecutively 43% in the ropeginterferon arm and 46% in the control arm.
However, after analyzing the CONTINUATION- PV study, it turned out that after 36 months of treatment, the rates of hematological responses begin to prevail in the group of patients receiving ropeginterferon, 53% versus 38% in the control group. Thus, from the above data, it can be seen that the response rate to ropeginterferon increases with the duration of treatment [23].
Another analysis of patients participating in the PROUD and CONTINUATION studies was based on the assessment of treatment results after 24 months, dividing patients into two groups according to age (under and over 60 years).
The initial comparison of both groups of patients showed that older patients had a more aggressive course of the disease. Patients over 60 years of age had a higher percentage of cells with a mutant JAK2 allele. They experienced both general symptoms and some complications, such as thrombosis, more frequently. Both patients under 60 years of age and over 60 years of age in the ropeginterferon arm had a higher rate of molecular response, namely 77.1 and 58.7% compared with the HU remission: 33.3 and 36.1%, respectively. Significantly higher reductions in the JAK2 allele were observed in both groups of patients after ropeginterferon treatment: it was 54.8% for younger patients and 35.1% for elderly patients. For comparison, this difference in the group of patients treated with HU was 4.5 and 18.4%, respectively.
What is more, the age did not affect the frequency of ropeginterferon side effects. In addition, the incidence of adverse ropeginterferon disorders was similar to that observed in the hydroxycarbamide group [24].
Essential thrombocythemia is a clonal growth of multipotential stem cells in the bone marrow. The consequence of this is increased proliferation of megakaryocytes in the bone marrow and an increase in the number of platelets in the peripheral blood. The level of platelets above 450,000/μl is considered a diagnostic criterion.
Essential thrombocythemia may progress over time to a more aggressive form of myeloproliferation, i.e., myelofibrosis. The disease can also evolve into acute myeloid leukemia or myelodysplastic syndrome, both with very poor prognosis. Thromboembolic complications are serious, and they concern over 20% of patients. Thrombosis occurs in the artery and venous area. Moreover, in patients with a very high platelet count, above 1,000,000/μl, bleeding may occur as a result of secondary von Willebrand syndrome [1, 2].
The treatment of ET is primarily aimed to prevent thrombotic complications.
In low-risk patients, only acetylsalicylic acid is used. In cases of high-risk patients, hydroxycarbamide is the first-line drug for most patients. Anagrelide and interferon are commonly used as second-line drugs.
Due to the possible effects of hydroxycarbamide of cytogenetic changes in the bone marrow cells after long-lasting usage, some experts recommend the use of interferon in younger patients in the first line. Interferon is also used as the drug of choice in patients planning a pregnancy [25].
The efficacy of pegylated interferon alpha-2a was assessed on the basis of the group of 39 patients with essential thrombocythemia and 40 patients with polycythemia vera.
Of the overall group, 81% of patients were previously treated prior to the study entry. The patients received pegylated interferon alpha-2a in a dose of 90 μg once a week. The dose of 450 μg was associated with a high percentage of intolerance.
In patients with essential thrombocythemia, the complete remission was achieved in 76%, while the overall hematological response rate brought 81%. Moreover, the molecular remission was achieved in 38%, in 14% of cases, JAK2 transcript became not detectable.
Patients diagnosed with polycythemia vera achieved 70% complete hematological remission and 80% general hematological response to treatment. JAK2 transcript was undetectable in 6% of patients. Molecular remission was achieved in 54% of cases.
Pegylated interferon alpha-2a at the dose of 90 μg per week was very well tolerated. In total, 20% of patients experienced a grade of 3 or 4 of adverse reaction, which was neutropenia. In addition, an increase in liver function tests was observed. Grade 4 of AE was not observed among patients who started the treatment with 90 μg/week while grade 3 neutropenia was an adverse event in only 7% of cases [26].
The effect of interferon alpha-2b treatment in patients with ET and PV was investigated. The study was prospective. Some of the results concerning the group of patients with polycythemia vera are presented in the subsection on polycythemia vera. In total, 123 patients with diagnosed essential thrombocythemia participated in the study. All of them received interferon alpha-2b. The patients were divided into two groups depending on the presence of the JAK2 V617F mutation. The enrolled patients were between 18 and 65 years of age. The treatment they received was, sequentially, interferon alpha-2b in the dose of 3 million units three times a week for the first 2 years, after which time the dose was changed into a maintenance dose, which amounted to 5 million units two times a week.
The analysis showed that the patients with the JAK2 V617F mutation present in a higher percentage achieved an overall hematological response as well as a complete hematological response. The overall hematological response was achieved in 83% of patients with JAK2 mutation, and the complete hematological remission was achieved in 23 cases. In the group of ET patients without the JAK2 V617F mutation, overall hematological response was achieved in 61.4%, while the complete hematological remission was achieved in 12 patients. The 5-year progression-free survival was obtained in 75.9% in the JAKV617F group and only in 47.6% without the mutation.
A significant proportion of patients experienced mild side effects. Grade 3 and 4 of adverse events were severe, most of them being a fever. The isolated cases of elevated liver tests and nausea have also been reported [19].
Pegylated interferon alpha-2b in patients with essential thrombocythemia who were previously treated with hydroxycarbamide, anagrelide, and other forms of interferon alpha, however, due to the lack of efficacy or toxicity, the patients required a change of treatment, was assessed. Pegylated interferon alpha-2b turned out to be effective in these cases. It led to the complete hematological remission in 91% of patients after 2 months of therapy, and in 100% of patients after 4 months. However, merely 11 patients participated in the study. Also only two patients required treatment discontinuation due to the side effects such as depression and general fatigue grade 3 [27].
In case of pregnant patients, interferon is currently considered the only safe cytoreductive drug. Over the years, several analyses of the results of interferon treatment during pregnancy have been carried out.
The assessment of 34 pregnancies in 23 women diagnosed with ET was performed retrospectively. All the pregnancies included in the analysis were of high risk. This high risk was associated with a high platelet count above 1,500,000/μl, a history of thrombotic episode, severe microcirculation disorders, or a history of major hemorrhage.
It turned out that the use of interferon allowed the birth of an alive child in 73.5% of cases. There was no difference in efficacy between the basic and pegylated forms of interferon alpha. In pregnancies without interferon treatment, the percentage of live births was only 60%. Moreover, it was not found if the presence of the JAK2 V617F mutation had any influence on the course of pregnancy [28].
An analysis of the course of pregnancy in patients with ET was assessed in Italy. Data from 17 centers were taken into account. Data from 122 pregnancies were collected from 92 women. In patients diagnosed with essential thrombocythemia, the risk of the spontaneous loss of pregnancy is about 2.5 times higher than among the general population. In the contrary to the study quoted above, it was found that the presence of the JAK2 mutation increases the risk of pregnancy loss. The proportion of live births in patients exposed to interferon during pregnancy was 95%, compared with 71.6% in the group of patients not treated with interferon.
The multivariate analysis also showed that the use of acetylsalicylic acid during pregnancy had no effect on the live birth rate of patients with ET [29].
Whatever its form, interferon is the drug of first choice in pregnancy. Hydroxycarbamide and anagrelide should be withdrawn for about 6 months, and at least for 3 months, before the planned conception. Experts recommend the use of interferon in high-risk pregnancies [30]. A Japanese analysis of 10 consecutive pregnancies in ET patients showed 100% live births in patients who received interferon [31].
In myelofibrosis (MF), monoclonal megakaryocytes produce cytokines that stimulate the proliferation of normal, non-neoplastic fibroblasts and stimulate angiogenesis. The consequence of this is the gradual fibrosis of the bone marrow, impaired hematopoiesis in the bone marrow, and the formation of extramedullary location mainly in the sites of fetal hematopoiesis, i.e., in the spleen and the liver.
The production of various cytokines by neoplastic megakaryocytes leads to the proliferation of normal, noncancerous fibroblasts as well as to increased angiogenesis.
Progressive bone marrow fibrosis leads to worsening anemia and thrombocytopenia. On the other hand, the production of proinflammatory cytokines by megakaryoblasts leads to the general symptoms such as weight loss, fever, joint pain, night sweats, and consequently, progressive worsening of general condition.
The prognosis for myelofibrosis is poor. In about 20% of patients, myelofibrosis evolves into acute myeloid leukemia with poor prognosis.
Currently, the only effective method of treatment that gives a chance to prolong the life is allogeneic bone marrow transplantation. However, this method is only available to younger patients.
The goal of treatment of patients who have not been qualified for allotranspalntation is to reduce the symptoms and to improve the patient’s quality of life. In case of leukocytosis cytoreducing drugs, such as hydroxycarbamide, melphalan, or cladribine can be used. They cause a reduction in the number of leukocytes and may, to some extent, inhibit splenomegaly. Interferon alpha has been used successfully for the treatment of myelofibrosis for many years. The results of its effectiveness will be presented below [2].
Currently, the JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis with enlarged spleen in intermediate and high-risk patients. Ruxolitinib reduces the size of the spleen, reduces general symptoms, and improves the quality of life; however, it does not prolong the overall survival of patients [32].
In 2015, the results of a retrospective study were published to compare the histological parameters of the bone marrow before and after interferon treatment. Twelve patients diagnosed with primary myelofibrosis as well as post-PV MF and post-ET MF were enrolled in the study. Patients were treated with pegylated recombinant interferon alpha-2a or recombinant interferon alpha-2b in standard doses. The time of treatment was from 1 to 10 years. Some patients had previously been treated with hydroxycarbamide or anagrelide. In all cases, karyotype was normal. The prognostic factor of Dynamic International Prognostic Scoring System (DIPSS) was assessed at the beginning as well as during the treatment.
Bone marrow cellularity decreased in cases with increased bone marrow cellularity before the treatment. After the interferon treatment, a reduction in the degree of bone marrow fibrosis was found. The parameters, such as the density of naked nuclei and the density of megakaryocytes in the bone marrow, also improved.
It proves that if the JAK2 V617F mutation had been present, DIPSS was decreased after interferon treatment. This relationship was not observed in patients without the JAK2 V617F mutation. The improvement in peripheral blood morphological parameters and the overall clinical improvement correlated with the improvement in the assessed histological parameters of the bone marrow.
Before the initiation of interferon, seven patients had splenomegaly. During the treatment with interferon, the complete resolution of splenomegaly was achieved in 17% of patients (two cases), and its size decreased in 25% (three cases). A good clinical response was achieved in 83% during interferon therapy. There was no significant difference in response between the two types of interferon used [33].
A prospective study was also conducted in patients with low and intermediate-1 risk group myelofibrosis. Seventeen patients were enrolled. Patients received interferon alpha-2b (0.5–3 milion units/three times a week) or pegylated interferon alpha-2a (45–90 μg/week). The duration of therapy was on average 3.3 years.
Most of the patients responded to the treatment. Partial remission was found in seven patients and complete remission in two patients. Moreover, in four cases, the disease was stabilized and in one case the clinical improvement was achieved. Three patients did not respond to treatment at all and progressed to myelofibrosis. Additionally, the assessment in reducing spleen size was performed. At baseline, 15 patients have splenomegaly, nine of them achieved the compete regression of spleen size [34].
However, the efficacy of interferon in the treatment of myelofibrosis appears to be limited only to a less advanced form, when the bone marrow still has an adequate percentage of normal hemopoiesis and the marrow stroma is not significantly fibrotic. In more advanced stages, interferon was not shown to have any significant effect on the regression of the fibrosis process [35].
In 2020, the results of the COMBI study were published. That was a two-phase, multicenter, single-arm study that investigated the efficacy and safety of the combination of ruxolitinib and pegylated interferon alpha. Thirty-two patients with PV and 18 patients with primary and secondary myelofibrosis participated in the study. The patients were at age 18 and older. Remission was achieved in 44% of myelofibrosis cases, including 28% (5 patients) of complete remission. In patients with PV, the results were slightly worse: 31% of remissions, including 9% of complete remissions. Patients received pegylated interferon alpha-2a (45 μg/week) or pegylated interferon alpha-2b (35 μg/week) in low doses and ruxolitinib in doses of 5–20 mg twice a day.
For the entire group of patients (with PV and MF), the initial JAK2 allele burden was 47% at baseline, and after 2 years of treatment with interferon and ruxolitinib, it decreased to 12%.
The treatment toxicity was low. The highest incidence of side effects occurred at initiation of therapy. It was mostly anemia and thrombocytopenia.
The observations from the COMBI study show that, for the combination of interferon in lower doses with ruxolitinib, it may be effective and well tolerated even in the group of patients who had intolerance to interferon used as the only drug in higher doses. The combined treatment improved the bone marrow in terms of fibrosis and its cellularity. It also allowed to improve the value of peripheral blood counts [36].
It is currently known that some of the additional mutations are associated with a worse prognosis in patients with myelorpoliferation, including patients with myelofibrosis. Some of these mutations have been identified as high-risk molecular mutations. These are ASXL1, EZH2, IDH1/2, or SRSF2. Earlier studies have shown their association with a more aggressive course of the disease, worse prognosis, and shorter survival of patients, as well as a poorer response to treatment. Due to their importance, they have been included in the diagnostic criteria of myelofibrosis [37].
It is also known that the presence of driver mutations, i.e., JAK2, CALR, and MPL or triple negativity, may affect the course of myeloproliferation, including the incidence of thromboembolic complications.
The assessment of the influence of driver mutations and a panel of selected additional mutations on the effectiveness of interferon treatment in patients with myelofibrosis was performed on a group of 30 patients. Only the patients with low- and intermediate-1-risk were enrolled in the study. The treatment with pegylated interferon alpha-2a or interferon alpha-2b resulted in a complete remission in two patients and partial remission in nine patients. The disease progressed in three cases. One patient relapsed and four died. The remaining patients achieved a clinical improvement or disease stabilization. In the studied group, it was not found if the effectiveness of interferon treatment was influenced by the lack of driver mutations. Among the group of four patients with additional mutations, two died and one had disease progression. It was a mutation of ASXL1 and SRSF2. The treatment with interferon in patients without additional molecular mutations in the early stages of the disease may prevent further progression of the disease [38].
The side effects of interferon in the group of patients with myelofibrosis are similar to those occurring after the treatment of other chronic myeloproliferative diseases. The most frequently described are hematological toxicity- anemia and thrombocytopenia, less often is the appearance of leukopenia. Hematological toxicity usually resolves with dose reduction or extension of the dose interval. The most frequently nonhematological toxicity was fatigue, muscle pain, weakness, and depression symptoms. All symptoms are usually mild and do not exceed grade 2 [38].
However, the use of interferon in the treatment of myelofibrosis has not been recommended as a standard therapy. Interferon is still being evaluated in clinical trials, or it is used in selected patients as a nonstandard therapy in this diagnosis.
Mastocytosis is characterized by an excessive proliferation of abnormal mast cells and their accumulation in various organs.
The basis for the development of mastocytosis is ligand-independent activation of the KIT receptor, resulting from mutations in the KIT proto-oncogene. The KIT receptor is a trans membrane receptor with tyrosine kinase’s activity. Its activation stimulates the proliferation of mast cells. That excessive numbers of mast cells infiltrate tissues and organs and release mediators such as histamine, interleukine-6, tryptase, heparin, and others, which are responsible for the appearance of symptoms typical of mastocytosis. In addition, the infiltration of tissues for mast cells itself causes damage to the affected organs.
The prognosis of mastocytosis depends on the type of the disease. In the case of cutaneous mastocytosis (CM), in the majority of cases prognosis is good and the disease does not shorten the patient’s life, but in aggressive systemic mastocytosis (ASM), the average follow-up is about 40 months. Mast cell leukemia has a poor prognosis with a median follow-up of approximately 1 year.
Systemic mastocytosis usually requires the implementation of cytoreductive therapy. The first line of therapy is interferon alone or its combination with corticosteroids. In aggressive systemic mastocytosis, the first line in addition to interferon 2-CdA can be used. An effective drug turned out to be midostaurin in the case of the present KIT mutation. In patients without the KIT D816V mutation, treatment with imatinib may be effective. In the case of mast cell leukemia, multidrug chemotherapy is most often required, as in acute leukemias, followed by bone marrow transplantation [39].
Systemic mastocytosis requiring treatment is a rare disease, this is why the studies available in the literature evaluating various therapies concern mostly small groups of patients.
In 2002, the French authors presented their experiences on the use of interferon in patients with systemic mastocytosis. They included 20 patients. The patients received interferon alpha-2b in gradually increased doses.
The patients were assessed after 6 months. In cases in which bone marrow was infiltrated for mast cells at baseline, it still remained infiltrated after 6 months of treatment.
However, the responses were obtained in terms of symptoms related to mast cell degranulation. Partial remission was achieved in 35% of patients and minor remission in 30%. It concerns mainly skin lesions and vascular congestion. Moreover, the assessment of the histamine level in the plasma revealed a decrease of it in patients who previously presented symptoms related to the degranulation of mast cells, such as gastrointestinal disorders and flushing.
A high percentage of side effects were found during treatment. They concerned 35% of patients. Depression and cytopenia were most frequent ones [40].
Another analysis was a report of five patients with systemic mastocytosis treated with interferon and prednisolone. All patients received interferon alpha-2b in a dose of 3 million units three times a week and four patients additionally received prednisolone. Four patients responded to interferon treatment at varying degrees. One patient, who at baseline had bone marrow involvement by mast cells in above 10%, progressed to mast cell leukemia. In two patients, the symptoms C resolved completely and in one of them they partially disappeared. In one case, stabilizing disease was achieved [41].
In 2009, a retrospective analysis of patients treated with cytoreductive therapy due to mastocytosis was published. The authors collected data from 108 patients treated at the Mayo Clinic. This analysis allowed for the comparison of the efficacy of four drugs used in systemic mastocytosis. There were interferon alpha alone or in the combination with prednisone—among 40 patients, hydroxycarbamide—among 26 ones, imatinib—among 22 persons, and 2-chlorodeoxyadenosine (2-CdA)—among 22 patients.
After dividing the patients into three additional groups on the basis of the type of mastocytosis—indolent systemic mastocytosis, aggressive systemic mastocytosis, and systemic mastocytosis associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD)—the effectiveness of each of type of therapy was assessed.
The highest response rates in indolent and aggressive mastocytosis were achieved with interferon treatment. They were 60% of the responses in both groups, and in the SM-AHNMD group of patients, the percentage was also one of the highest and amounted to 45%. The second most effective drug was 2-CdA. The response rates were 56% for indolent MS, 50% for aggressive MS, and 55% for SM-AHNMD. The patients treated with imatinib achieved response in 14, 50, and 9% by following groups, respectively. In contrast, patients with indolent and aggressive systemic mastocytosis did not respond to hydroxycarbamide treatment at all. The response rate in both groups was 0%. However, patients with MS associated with another clonal hematological nonmast cell lineage disease achieved 21% response to hydroxycarbamide. Additionally, it was found that only interferon relieved symptoms caused by the release of inflammatory mediators by mast cells.
The additional analysis showed no influence of the TET 2 mutation on the response to treatment [42].
In the literature, there are also single cases of mastocytosis presenting trials of nonstandard treatment. That is description of a patient with systemic mastocytosis with mast cell bone marrow involvement. Mutation of c-kit Asp816Val was present. Patient progressed despite treatment with dasatinib and 2-chlorodeoxyadenosine. The patient developed symptoms related to the degranulation of mast cells and increased ascites.
The patient was treated with pranlukast, which is an anti-leukotriene receptor antagonist due to an asthma episode. The rate of ascites growth decreased significantly after one administration. The patient required paracentesis every 10 days and not every 3 days, as before starting to take the drug. After 15 days of treatment with pranlukast, the patient received interferon alpha, which resulted in complete regression of ascites, resolution of pancytopenia, and complete disappearance of the c-kit mutation clone. The infiltration of mast cells in the bone marrow significantly decreased [43].
Interferon alpha was also effective in a patient with systemic mastocytosis associated with myelodysplastic syndrome with the c-kit D816V mutation, which was refractory to imatinib treatment [44].
Interferon alpha also proved to be effective in the treatment of osteoporotic lesions appearing in the course of mastocytosis.
The series of 10 cases with resolved mastocytosis and osteoporosis-related fractures was presented in 2011. The patients received interferon alpha in a dose of 1.5 million units three times a week as well as pamindronic acid. The patients were treated for an average of 60 months. For the first 2 years, pamindronate was given at a dose of 1 mg/kg every month, and then every 3 months.
During the course of the study, no patient had a new-bone fracture. The level of alkaline phosphatase decreased by 25% in relation to the value before treatment and tryptase by 34%. Bone density increased during treated with interferon and pamindronate. The increase was on average 12% in the spine bones and 1.9% in the hip bones. At the same time, there was no increase in the density of the hip bone and a minimal increase in the density of the spine in patients treated with pamindronate alone.
The results of this observation suggest that it is beneficial to add low doses of interferon alpha to pamindronate treatment in terms of bone density increase [45].
That experiences show that interferon used in systemic mastocytosis significantly improves the quality of life of patients by inhibiting the symptoms caused by degranulation of mast cells. They prevent bone fractures and, in some patients, they cause remission of bone marrow infiltration by mast cells.
Chronic neutrophilic leukemia (CNL) is a very rare disease. It is characterized by the clonal proliferation of mature neutrophils.
The diagnostic criteria proposed by the World Health Organization (WHO) comprise leukocyte counts above 25,000/μl (including more than 80% of rod and segmented
Physical examination often shows enlargement of the liver and spleen, moreover, patients complain on weight loss and weakness [1].
The prognosis varies. The average survival time for patients with CNL is less than 2 years.
Only few descriptions of chronic neutrophilic leukemia are available in the literature, and these are mostly single case reports.
Because it is an extremely rare disease, there are no established and generally accepted treatment standards. In most cases, patients are given hydroxycarbamide or interferon. Patients who are eligible for a bone marrow transplant may benefit from this treatment. Bone marrow allotransplantation remains the only method that gives a chance for a significant extension of life.
The German authors presented a series of 14 cases of chronic neutrophilic leukemia. The group of patients consisted of eight women and six men. The average age was 64.7 years. From the entire group of patients, longer survival was achieved only in three cases. One of these patients was treated with interferon alpha and achieved hematological remission, the other underwent bone marrow allotransplantation from a family donor, and the third one was treated with hydroxycarbamide and transfusions as needed. The follow-up period of the patient after allogeneic matched related donor transplantation (allo-MRD) was 73 months, and for the patient after interferon treatment it was 41 months.
The remaining patients died within 2 years of diagnosis. Six patients, the largest group, died due to intracranial bleeding, three patients died because of leukemia cell tissue infiltration, one patient because of the disease transformation into leukemia, and one patient because of pneumonia [46].
It can be seen from these experiences that treatment with interferon alpha can significantly extend the survival time of patients.
The case of a 40-year-old woman diagnosed with chronic neutrophilic leukemia is presented by Yassin and coauthors. Initially, the patient had almost 41,000 leukocytes in the peripheral blood. In a physical examination, splenomegaly and hepatomegaly were not present. Patient received pegylated interferon alpha-2a. The initially dose was 50 μg once a week for the first 2 weeks, then the dose was increased to 135 μg weekly for 6 weeks, and then the dose interval was extended to another 2 weeks. As a result of the treatment, the general condition of the patient improved and the parameters of peripheral blood counts were normalized [47].
Another case report presented in the literature describes a 41-year-old woman diagnosed with CNL accompanied by focal segmental glomerulosclerosis (FSGS). The patient had increasing leukocytosis for several months. On the admission to the hospital, leukocytosis was 94,000/μl. Moreover, the number of platelets in the morphology exceeded 1,000,000/μl. More than a year earlier, the patient had splenectomy due to splenomegaly and spleen infraction.
Additionally, JAK2 V617F mutation was found. Some authors suggest that the presence of JAK2 mutation may be associated with longer survival in CNL.
The patient received hydroxycarbamide for 3 months and reduction in the number of leukocytes was achieved. After this time, interferon alpha-2b was added to hydroxycarbamide. As a result, focal segmental glomerulosclerosis disappeared and the renal tests improved [48].
Another case of chronic neutrophilic leukemia with a JAK2 gene mutation concerns a 53-year-old man. The patient’s baseline leukocytosis was 33,500/μl, including the neutrophil count of 29,700/μl. The patient also had splenomegaly.
The treatment with interferon alpha-2b at a dose of 3 million units every other day was started. After a month of treatment, the number of leukocytes was reduced to less than 10,000/μl. Then the patient was treated chronically with interferon alpha-2b in doses of 3 million units every 2 weeks. As a result of the therapy, the number of leukocytes remains between 8 and 10,000/μl. The patient remains in general good condition [49].
A series of two CNL cases are also shown. The first patient was a 70-year-old woman with stable leukocytosis of about 35,000/μl and the remaining morphology parameters in normal range. The patient was only observed for 5 years until hepasplenomegaly progressed rapidly. Then, interferon alpha-2b was included. Due to the treatment, the rapid regression of hepatosplenomegaly was achieved.
The second case is a 68-year-old woman with baseline leukocytosis of almost 14,000/μl. In this case, the treatment with hydroxycarbamide was started immediately. However, no improvement was achieved. After 6 weeks of HU treatment, interferon alpha-2b 3 million units 3 times a week was implemented and leukocytosis decreased. Due to the interferon treatment, the disease stabilized for a long time. Because the patient experienced an adverse reaction, a severe flu-like syndrome, interferon was discontinued. After interferon withdrawal, the disease progressed gradually and the treatment attempts by busulfan and 6-mercaptopurine were unsuccessful. Therefore, interferon was readministered and the disease went into remission. Interferon treatment was continued at a reduced dose. The disease regression was achieved again.
Additionally, the patient showed an improvement in the function of granulocytes in terms of phagocytosis and an improvement in neutral killer (NK) cell function after treatment with interferon [50].
The above examples show that interferon alpha is effective in the treatment of chronic neutrophilic leukemia. The side effects are rare and can be managed with dose reductions. Moreover, in these cases, interferon is also effective in a reduced dose. Disease remission or regression can be achieved without typical of CNL complications, such as intracranial bleeding.
Interferon has been used in the past to treat chronic myeloid leukemia. The treatment with tyrosine kinase inhibitors is now a standard practice. However, in a small number of patients, they are ineffective or exhibit unmanageable toxicity. Therefore, the attempts are underway to use interferon in combination with TKI in lower doses, which is to ensure the enhancement of the antiproliferative effect while reducing the toxicity.
There are ongoing attempts to use ropeginterferon in patients diagnosed with chronic myeloid leukemia, in whom treatment with imatinib alone has not led to deep molecular response (DMR). The first phase study was conducted in a small group of patients with chronic myeloid leukemia. The patients in first chronic phase treated with imatinib who did not achieve DMR, but in complete hematologic remission and complete cytogenetic remission, were included in the study. Patients have been treated with imatinib for at least 18 months. Twelve patients were enrolled in the study, and they completed the study according to the protocol. These patients received additional ropeginterferon to imatinib and four achieved DMR. Low toxicity was observed during the treatment. Among the hematological toxicities, neutropenia was the most common. There was no nonhematological toxicity with a degree higher than 1/2 during the treatment. Moreover, it has been found that better effects and fewer side effects are obtained when ropeginterferon is administered for a longer time, but in lower doses. The comparison of the effectiveness of interferon in chronic myeloproliferative disorders based on selected articles is presented in Table 1 [51].
Source | Type of trial | Interferon | Diagnosis | No. | Prior treatment status | Response rate |
---|---|---|---|---|---|---|
Yacoubet al. [15] | Phase II, multicenter | Pegylated IFN alfa-2a | PV | 50 | Resistance to HU or HU intolerance | CR:22% PR:38% |
ET | 65 | CR:43% PR:26% | ||||
Masarova et al. [16] | Phase II, single-center | Pegylated IFN alfa-2a | PV | 43 | Untreated or previously treated with cytoreductive therapy | CR:77% PR:7% |
ET | 40 | CR:73% PR:3% | ||||
Samuelsson et al. [18] | Phase II | Pegylated IFN alfa-2b | PV | 21 | Untreated or previously treated with cytoreductive therapy | CR: 69% for the entire group |
ET | 21 | |||||
Huang BT et al. [19] | Open label, multicenter | IFN alfa-2b | PV | 136 | Untreated or previously treated with cytoreductive therapy | OHR:70% Molecular response:54.7% |
ET | 123 | OHR (JAK2+ patients):83% CHR:23 cases OHR (JAK2-patients): 61.4% CHR:12 cases | ||||
Gisslinger et al. [23] | phase III, multicenter | Ropeginterferon | PV | 257 | Previously treated | OHR:53% |
Quintás-Cardama et al. [26] | phase II | Pegylated IFN alfa-2a | PV | 40 | Untreated or previously treated with cytoreductive therapy | OHR:80% CR:70% Molecular remission:54% |
ET | 39 | OHR:81% CR:76% Molecular remission:38% | ||||
Sørensen et al. [36] | Phase III, multicenter, COMBI | Pegylated IFN alfa-2a with ruxolitinib or Pegylated IFN alfa-2b with ruxolitinib | PV | 32 | Untreated or previously treated with cytoreductive therapy | OHR:44% CR:28% |
MF | 18 | OHR:31% CR:9% | ||||
Casassus et al. [40] | Open label, multicenter | IFN alpha-2b | Mastocytosis | 20 | Untreated and previously treated | PR:35% Minor remission: 30% |
Comparison of the effectiveness of interferon in chronic myeloproliferative disorders.
PV: polycythemia vera; ET: essential thrombocythemia; MF: myelofibrosis; HU: hydroxycarbamide/hydroxyurea; CR: complete remission; PR: partial remission; and OHR: overall hematological response.
Interferon alpha appears to be an effective and safe drug in the most type of chronic myeloproliferative disorders. Nowadays, all forms of its using have similar effectiveness. Interferon alpha can be effective even in cases of resistance for first-line treatment. Trial research is currently underway to combine it with some new drugs, such as ruxolitinib, and to add it to the already well-established therapy, it is a promising option for patients with refractory disease.
From time to time, new forms of interferon, such as ropeginterferon, are introduced, which gives hope for better effectiveness, better safety profile, and greater comfort in its use for patients who have to be treated for many years. In the case of the use of interferons alpha in the treatment of chronic myeloproliferative diseases, there are still opportunities to extend its use and to study its combination with newly introduced drugs.
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\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"10",type:"subseries",title:"Animal Physiology",keywords:"Physiology, Comparative, Evolution, Biomolecules, Organ, Homeostasis, Anatomy, Pathology, Medical, Cell Division, Cell Signaling, Cell Growth, Cell Metabolism, Endocrine, Neuroscience, Cardiovascular, Development, Aging, Development",scope:"Physiology, the scientific study of functions and mechanisms of living systems, is an essential area of research in its own right, but also in relation to medicine and health sciences. The scope of this topic will range from molecular, biochemical, cellular, and physiological processes in all animal species. Work pertaining to the whole organism, organ systems, individual organs and tissues, cells, and biomolecules will be included. Medical, animal, cell, and comparative physiology and allied fields such as anatomy, histology, and pathology with physiology links will be covered in this topic. Physiology research may be linked to development, aging, environment, regular and pathological processes, adaptation and evolution, exercise, or several other factors affecting, or involved with, animal physiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. 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