Levels of hypoglycemia proposed when reporting in clinical trials and as defined by the ADA.
\r\n\t
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Currently, he is an Associate Professor at Physics Department, Kasetsart University, Thailand. He is a specialist in the development of smart sensors and intelligent systems for food, agricultural and environmental applications. He has received over twenty-eight research awards such as TRF–OHEC–SCOPUS Young Researcher Award in physical science, Invention Award from National Research Council of Thailand, Highest Citation Award for the young researcher, etc. He has served as a reviewer, guest editor, and associate editor for several scientific journals. He is Top 2% World Ranking of Scientists in Electrical & Electronic Engineering in 2020 and 2021 ranked by the Stanford University researcher team. He has published several dozens of articles in reputed journals, proceedings, book chapters, patents, and copyrights. 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Descartes’ rule of signs has been studied and generalized by many authors over the years; one of the earliest can be found in [7], see also [4, 11]. (For some recent contributions, see [1, 2, 6, 10, 12, 14], to mention a few.)
In the present survey, we summarize a relatively new development in this area which, to the best of our knowledge, was initiated only in the 1990s (see [12]).
For simplicity, we consider below only real univariate polynomials with all nonvanishing coefficients. For a polynomial
It is true that for a given SP with
One can apply Descartes’ rule of signs to the polynomial
A natural question apparently for the first time raised in [12] is whether one can freely combine these two results about the numbers of positive and negative roots. Namely, given a SP
If such a polynomial exists, then we say that it
It is clear that if a couple (SP, AP) is realizable, then it can be realized by a polynomial with all simple roots, because the property of having nonvanishing coefficients is preserved under small perturbations of the roots.
In this short survey, we present what is currently known about Problem 1. After the pioneering observations of Grabiner [12] which started this line of research, important contributions to Problem 1 have been made by Albouy and Fu [1] who, in particular, described all non-realizable combinations of the numbers of positive and negative roots and respective sign patterns up to degree
On the other hand, besides Problem 1 as it is stated, there is a significant number of related basic questions which can be posed in connection to the latter Problem and are still waiting for their researchers. (Very few of them are listed in Section 5.)
One should also add that there is a number of completely different directions in which mathematicians are trying to extend Descartes’ rule of signs. They include, for example, rule of signs for other univariate analytic functions including exponential functions, trigonometric functions and orthogonal polynomials, multivariate Descartes’ rule of signs, tropical rule of signs, rule of signs in the complex domain, etc. (see, e.g., [6, 10, 14]) and references therein. But we think that Problem 1 is the closest one to the original investigations by Descartes himself.
The structure of this chapter is as follows. In Section 2, we provide the information about the solution of Problem 1 in degrees up to 11. In Section 3, we present several infinite series of non-realizable couples (SP, AP). Finally, in Section 4 we discuss two generalizations of Problem 1 and their partial solutions.
Let us start with the following useful observation.
To shorten the list of cases (SP, AP) under consideration, we can use the following
and the second one acts by
Obviously, the first generator exchanges the components of the AP. Concerning the second generator, to obtain the SP defined by the polynomial
It is obvious that all pairs or quadruples (SP, AP) constituting a given orbit are simultaneously (non-)realizable.
As a warm-up exercise, let us consider degrees
Here, both SPs are symmetric w.r.t. its middle.
For
The first of the SPs is symmetric, and the second one is antisymmetric w.r.t. their middles.
Finally, for
constitute one orbit for
It turns out that for
It is clear that these two cases constitute one orbit of the
realizes the second of these couples and has two positive roots
For
where Res
It remains to be noticed that for
For degrees
(2)
The two cases of Part (1) of Theorem 2 also form an orbit of the
For
The lengths of the respective orbits in these
The case
The lengths of the respective orbits are
Observe that for
There is a strong evidence that for
is also non-realizable. (Its Descartes’ pair equals
Summarizing the above, we have to admit that the information in low degrees available at the moment does not allow us to formulate a consistent conjecture describing all non-realizable couples in an arbitrary degree which we could consider as sufficiently well motivated.
In this section we present a series of couples (non-)realizable for infinitely many degrees. We decided to include those proofs of the statements formulated below which are short and instructive.
Our first examples of realizability deal with polynomials with the minimal possible number of real roots:
Our next example deals with
Proposition 2 will follow from the following
The concatenation lemma allows to deduce the realizability of couples (SP, AP) with higher values of
When
and the SP of
When
and the SP of
For
define the SPs
For
With the AP
With the AP
Our next result discusses (non-)realizability for polynomials with only two sign changes (see [8, 9]).
Certain results about realizability are formulated in terms of the ratios between the quantities
Suppose that the degree
Suppose now that the degree
One can observe that Cases (1), (2), and (3) exhaust all possible APs
In this section, we consider realization problems similar or motivated by Problem 1. A priori it is hard to tell which of these or similar problems might have a reasonable answer.
Consider a real polynomial
Now, for
The following question where a positive answer to which can be found in [15] seems very natural.
Now, we are going to formulate a problem which is a refinement of both Problems 1 and 2.
Recall that for a real polynomial
It is always true that
as well as the inequalities (5)–(6). Then, we say that
is a
Nevertheless, in order to make comparisons with Problem 1 more easily, we consider couples (SP, SAP) instead of just SAPs. But for a given SP, there are, in general, several possible SAPs which is illustrated by the following example.
For
respectively. One can show that
Indeed, by Rolle’s theorem, the derivative of a polynomial realizing the couple
Our final realization problem is as follows:
(2) Obviously, Problem 3 is a refinement of Problem 2—in the latter case, one does not take into account the signs of the real roots of the polynomial and its derivatives.
(3) When we deal with couples (SP, SAP), we can use the
The following proposition is proven in [5]:
One can choose such a polynomial
In the same way, for odd
by some hyperbolic polynomial
For
A. For
B. For
and only it (up to the
One can observe that the couple
C. For
The non-realizability of the first four of them follows from that of the couple
One of the methods used in the study of couples (SP, AP) or (SP, SAP) is the explicit construction of polynomials with multiple roots which define a given SP. Such constructions are not difficult to carry out because one has to use families of polynomials with fewer parameters. Once a polynomial with multiple roots is constructed, one has to justify the possibility to deform it continuously into a nearby polynomial with all distinct roots. Multiple roots can give rise to complex conjugate pairs of roots. An example of such a construction is the following lemma from [5].
Our first open question deals with the limit of the ratio between the quantities
A priori, for
A less ambitious open problem is to find an interval
A related problem would be to find sufficient conditions for realizability based on the ratios between the quantities
Our third open question is about the realizability of couples (SP, SAP). For
Our final natural and important question deals with the topology of intersections of the set of real univariant polynomials with a given number of real roots with orthants in the coefficient space (which means fixing the signs of the coefficients). It is well known that the set of monic univariate polynomials of a given degree and with a given number of real roots is contractible. When we cut this set with the union of coordinate hyperplanes (coordinates being the coefficients of polynomials), then it splits into a number of connected components. In each such connected component, the number of positive and negative roots is fixed. But, in principle, it can happen that different connected components correspond to the same pair (pos, neg). Could this really happen? Are all such connected components contractible, or they can have some nontrivial topology?
The authors want to thank the Department of Mathematics of the Université Côte d’Azur and Stockholms Universitet for the hospitality, financial support, and nice working conditions during our several visits to each other.
Diabetes is a lifelong, chronic disease characterized by episodes of hyperglycemia [1, 2]. Treatment of diabetes, in order to be effective, must lower glucose concentration to a euglycemic level, however, the key barrier to optimal glycemic control is hypoglycemia (low blood glucose levels) despite ongoing improvements in therapies and technology [3].
Hypoglycemia is one of the most impactful adverse events in diabetes and is a common problem for people with both type one (T1D) and type two (T2D) diabetes [4]. Too much insulin or, insulin-producing medications are commonly related to a hypoglycemic event, however other factors such as delayed, missed, or reduced meals other than what was planned, unanticipated strenuous exercise, alcohol consumption or interactions with other drugs are also known contributors. Additionally, individual patient factors such as older age, nutritional status, duration of diabetes, renal or hepatic disease, history of hypoglycemic episodes [5], and hypoglycemic unawareness may increase the risk of events [6].
Despite recent advances in diabetes technology, hypoglycemia remains a key obstacle to achieving adequate glycemic control [3, 7, 8]. Even though the issue is well accepted, the size of the issue varies depending on how hypoglycemia is defined, measured, and reported. The incidence of hypoglycemia reported between randomized controlled trials vs. observational studies vs. patient-reported outcomes was found to differ by a factor of over 100 in one review [9].
The frequency of hypoglycemia varies from 42 to 91 events per patient year for adults with Type 1 diabetes (T1D) and from 20.3–44.4 events per patient year for adults with Type 2 diabetes (T2D) [10]. Severe hypoglycemia is not only a problem for insulin-treated patients but is also common among older adults with T2D across all levels of glycemic control. The risk tends to be higher in patients with either near-normal glycemia or very poor glycemic control [4]. Additionally, frequent episodes of mild hypoglycemia may compromise the hormonal counterregulatory response to produce adrenaline and subsequent autonomic warning symptoms such as trembling and sweating leading to hypo-unawareness increasing the risk of severe hypoglycemia further [6].
With the general exception of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS), the clinical consequences of prolonged hyperglycemia are long-term. These long-term risks were demonstrated in the Diabetes Control and Complications Trial (DCCT) [11] and the United Kingdom Prospective Diabetes Study (UKPDS) [12] for T1 and T2 diabetes respectively and are the result of neuropathy, retinopathy, and/or nephropathic complications.
The clinical consequences of severe hypoglycemia on the other hand can be immediately associated with the event and include acute cerebrovascular disease, myocardial infarction, neurocognitive dysfunction, and loss of vision [13]. If left untreated, severe hypoglycemia can result in significant morbidity and mortality [14, 15].
All levels of hypoglycemia are associated with significant indirect costs, not only on employers but also on individuals with diabetes [16]. A recent study showed a clear link between severe hypoglycemia and the costs of lost productivity, with the highest loss in productivity attributed to non-severe nocturnal hypoglycemic events [17]. Numerous studies have shown that hypoglycemia negatively impacts patients’ ability to concentrate and participate in daily activities, thereby negatively impacting the quality of life (QoL) [17]. Even non-severe hypoglycemia, which occurs in 24–60% of patients with diabetes, can adversely affect QoL [18]. The greatest reductions in QoL are seen among those participants reporting a higher frequency of non-severe hypoglycemia [18]. As reported by Geelhoed-Duijvestijn et al., it takes an average of 50.4 min to return to normal functioning following a daytime non-severe hypoglycemic event, but negative feelings persisted for an average of 5.4 hours [19]. Following a nocturnal non-severe hypoglycemic event, functionality was diminished for an average of 80.5 min while negative feelings persisted for 12.2 hours [19].
Severe hypoglycemic episodes not only significantly affect the individual but are associated with long-term cost implications to the health system. One cohort study assessed the costs between a population requiring hospitalization due to severe hypoglycemia and a matched control. The results demonstrated that the group suffering from the severe hypoglycemic episode incurred an additional $10,873 (p < 0.001) in direct and indirect costs vs. the control for that event year [20].
Hypoglycemia detection and management remain the cornerstone of modern diabetes management and it is important that patients and their healthcare providers (HCPs) understand the strengths and limitations of various blood glucose monitoring systems (BGMS) in order to select the most appropriate system that meets their individual needs [13].
A joint position statement of the International Hypoglycemia Study Group of ADA and EASD has proposed three glucose severity levels when reporting hypoglycemia in clinical trials of glucose-lowering drugs for the treatment of diabetes (Table 1). The Group recommends that the frequency of detection of a glucose concentration < 3.0 mmol/l (<54 mg/dl), which it considers to be clinically significant biochemical hypoglycemia, should be included in clinical trial reports [21]. These levels are further aligned by the most recent version of the ADA’s Standards of Medical Care in Diabetes 2022 (Table 1).
ADA – Standards of Care 2022 | International Hypoglycaemia Study Group., 2017 | |
---|---|---|
Level 1 < 70–54 mg/dL (3.9–3.0 mmol/L) with or without symptoms | Considered clinically important (independent of the severity of acute hypoglycemic symptoms) | This need not be reported routinely in clinical studies, although this would depend on the purpose of the study |
Level 2 < 54 mg/dL (3.0 mmol/L) with or without symptoms | The threshold at which neuroglycopenic symptoms begin to occur and require immediate action to resolve the hypoglycemic event | Sufficiently low to indicate serious, clinically important hypoglycemia |
Level 3 Severe hypoglycemia not defined by a specific glucose level | Defined as a severe event characterized by altered mental and/or physical functioning that requires assistance from another person for recovery | Severe cognitive impairment requiring external assistance for recovery |
Levels of hypoglycemia proposed when reporting in clinical trials and as defined by the ADA.
According to current ISO 15197:2013 accuracy requirements, ≥95% of BG results should be demonstrated to be within ±15% of the reference method for samples with BG concentrations ≥100 mg/dL, and ± 15 mg/dL when BG concentrations are <100 mg/dL. (International Organization for Standardization.)
The FDA guidance 2020 recommends that ≥95% of all BGMS results should be within ±15%, and ≥ 99% of all BGMS results should be within ±20% of the reference laboratory method across the entire claimed to measure range of the BGMS. (US Department of Health and Human Services [22]. Food and Drug Administration.)
These more stringent guidelines recognized the limitations of evaluating BG samples at the extreme ends of the measuring range, especially in the low range where very few samples are available [23]. Recognizing the clinical importance of the accuracy of BG measurements for hypo- and hyperglycemic blood samples, both European and US authorities have requested that accuracy data be reported separately for low, normal, and high BG ranges [23]. This issue is however complicated by system accuracy requirements being applied to measurement results from the whole glycemic range. If a BGMS shows 100% accurate results at BG concentrations ≥80 mg/dL (4.44 mmol/L) (80% of results, following ISO 15197:2013) [24], this results in 25% of the samples in the low-glucose range being allowed outside the accuracy limits (5% “results outside of accuracy limits” divided by 20% “results <80 mg/dL [4.44 mmol/L]”) [23].
Despite the boundaries of ISO 2013 standards and/or FDA 2020 guidance, (International Organization for Standardization., US Department of Health and Human Services [22]. Food and Drug Administration) considerable differences exist in the performance of commercially available BGMS [25]. Such error patterns over the operating range of BGMS may lead to relevant differences in clinical and economic outcomes. These differences can potentially increase the risk of not detecting hypoglycemic events when they occur, and, therefore, inadequately identifying and treating them [25].
Thus, if a patient’s true BG concentration is 60 mg/dL (3.33 mmol/L), acceptably accurate results range from 45 to 75 mg/dL (2.50 to 4.16 mmol/L) according to the ISO limits and from 51 to 69 mg/dL (2.83 to 3.83 mmol/L) according to FDA criteria. This can make it difficult for a patient to detect and manage their hypoglycemia. If a BGMS cannot reliably differentiate between 50, 60, and 70 mg/dL (2.77, 3.33, and 3.88 mmol/L), the utility of predefined hypoglycemia thresholds comes into question [23].
Multiple post-market studies of BGMS have failed to replicate the accuracy normally required to gain market approval by the regulatory authorities [26, 27, 28, 29, 30]. Many of these products remain on the market today.
Whilst it is not difficult to obtain BG samples in the normal range it is more of a challenge to obtain and subsequently assess the accuracy of devices outside of this range. It may be unethical and potentially dangerous to purposefully cause hypoglycemia in a patient simply for the purposes of testing device accuracy. The remaining choices to assess accuracy at this level is either to accept the smaller sample size, modify the sample prior to testing, or to create a statistical model. These concepts have further been explored in the low blood glucose range and evidence shows that the accuracy of different BGMS (that were approved under ISO 2013 standards) are not the same at these critical levels and some would appear non-compliant [29, 31]. Recently a methodology was developed to demonstrate the differences in accuracy in the low blood glucose range among several BGMSs as demonstrated in Figure 1 [32, 33, 34, 35]. The differences in accuracy between devices was clinically meaningful.
Probability curves for real-world BGMSs (all meeting ISO 15197:2013 criteria) (adapted from [
Continuous glucose monitoring (CGM) devices have become more widespread over the past decade. They generally fall into two categories, real-time (rt-CGM) and intermittently scanned (is-CGM) devices. rt-CGM has shown positive improvements in improving HbA1c and reducing hypoglycemia in insulin users in RCTs [36, 37, 38] whereas is-CGM generally relies on observational data to support its use [39]. They predominantly differ from BGMS by measuring glucose concentration in the interstitial fluid, several times per hour, whereas BGMS measure blood (normally capillary) glucose once per test, up to around 10 times per day, depending on individual patient needs [1].
Unlike BGMS that have well-defined FDA and ISO accuracy criteria that must be met prior to obtaining marketing authorization, there remains no such standardized metrics for CGM accuracy requirements. In spite of this, it is commonplace for manufacturers to describe the accuracy of a CGM using Mean Absolute Relative Difference (MARD). This is calculated by averaging the absolute values of relative difference from the comparison method and does not account for positive or negative bias, i.e. all differences are made positive [40]. The MARD of some CGM systems has been reported to be in the 10–12% range whereas some BGMS has demonstrated to be below 5% [40].
One reason for the difference in MARD between some CGMs and BGMS could be attributed to measuring glucose in different compartments of the body. There is an inherent delay between glucose levels in each compartment with one study suggesting that to be between 6 and 10 minutes [41]. This makes it very difficult for a CGM to be as accurate, particularly at times of rapid glucose change. A further study demonstrated that MARD could change considerably throughout the day, approximately doubling between fasting periods and after food (8.0–16.3% and 9.1–16.3% depending on the device) [42]. This brings into question the value of such a metric if it can vary so much. Table 2 provides some examples of when BGM is needed in CGM users.
|
|
|
|
Some examples for adjunct blood glucose testing in CGM users.
ISF: interstitial fluid; CGM: continuous glucose monitoring; EU: European Union; and UK: United Kingdom.
Additionally, the detection of hypoglycemia by a CGM device is dependent on the duration of the hypoglycemic event. A recent study showed that two-thirds of all patients reported hypoglycemic events required minimum duration of 15 minutes in order to be by the CGM device [43].
A low ISF glucose reading below 3.9 mmol/L can prompt corrective actions that may be unnecessary if actual blood glucose, as measured by SMBG, is significantly higher. For instance, a user may develop hypoglycemia and take corrective action. Due to the time lag between blood glucose and ISF glucose, if the user continues to rely only on ISF glucose readings, there may be a lag in the rise of ISF over blood glucose, resulting in further and unnecessary treatment of hypoglycemia.
Similarly, experienced users may become less concerned with ISF low glucose readings than they would be with SMBG readings and take no immediate action. Each of these scenarios potentially creates unwanted risks [44].
The use of a CGM, particularly for the management of T1D, is preferred; however, all patients should learn how to use a BGMS for backup and monitoring if CGM is not available and/or desired [39]. This was further confirmed by the American Diabetes Association [1] which stated, “Every patient using a CGM must have a BGM.” The reasoning for using a BGM when using a CGM includes whenever there is suspicion that the CGM is inaccurate, while waiting for warm-up, for calibration (some sensors) or if a warning message appears, and in any clinical setting where glucose levels are changing rapidly (>2 mg/dL/min), which could cause a discrepancy between CGM and BGM readings.
The definition of hypoglycemia is based on blood glucose readings, therefore the use of BGM in CGM users remains an essential part of their diabetes management.
The American Association of Clinical Endocrinologists and American College of Endocrinology 2016 outpatient glucose monitoring consensus statement provided clinical situations and patients groups requiring the highest possible accuracy in glucose monitoring for detection of hypoglycemia [45]. These include those with a history of severe hypoglycemia; hypoglycemia unawareness; infants and children receiving insulin therapy; patients at risk for hypoglycemia, including patients receiving basal insulin or basal/bolus insulin therapy, patients with irregular schedules, skipped or small meals, vigorous exercise, travel between time zones, disrupted sleep schedules, shift work, and people with occupational risks that enhance possible risk from hypoglycemia (e.g., driving or operating hazardous machinery) [45].
Other patient groups include those receiving sulfonylurea or glinides [46], and people with diabetes with comorbidities such as hyperlipidemia or chronic renal disease who may also be taking multiple medications [47]. Age is also an important factor, as risk factors for hypoglycemia such as renal impairment, cardiovascular disease, and polypharmacy all increase with advancing age in adults with T2D [48, 49, 50].
The high accuracy in the low blood glucose range is also necessary for diabetes management during pregnancy, therefore CGM use in this patient population remains adjunctive use only [45, 51]. Blood glucose monitoring remains a cornerstone of glucose management during pregnancy [1].
In order to make correct therapy decisions, a correct glucose reading is essential [52]. In order to obtain a correct glucose reading, the correct device must be used. This selection spans both device types, i.e. CGM/BGM, and also specific device within the type. Accuracy variation within both system types is proven to be significant, therefore understanding the importance of education for HCP and patients to make an informed choice based on individual needs.
Medical writing was supported by Madano.
RS and JR are employees of Ascensia Diabetes Care Holdings AG.
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Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}},{id:"351158",title:"Prof.",name:"David W.",middleName:null,surname:"Anderson",slug:"david-w.-anderson",fullName:"David W. Anderson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Calgary",country:{name:"Canada"}}}]}},subseries:{item:{id:"92",type:"subseries",title:"Health and Wellbeing",keywords:"Ecology, Ecological, Nature, Health, Wellbeing, Health production",scope:"\r\n\tSustainable approaches to health and wellbeing in our COVID 19 recovery needs to focus on ecological approaches that prioritize our relationships with each other, and include engagement with nature, the arts and our heritage. This will ensure that we discover ways to live in our world that allows us and other beings to flourish. We can no longer rely on medicalized approaches to health that wait for people to become ill before attempting to treat them. We need to live in harmony with nature and rediscover the beauty and balance in our everyday lives and surroundings, which contribute to our well-being and that of all other creatures on the planet. This topic will provide insights and knowledge into how to achieve this change in health care that is based on ecologically sustainable practices.
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