**4.7 Return to Play**

Few studies have reported on return to play after patellar stabilization in patients with patellofemoral instability [142–145].

Schneider and associates [142] performed a systematic review and meta-analysis to evaluate the outcomes of isolated MPFL reconstruction for the treatment of recurrent patellofemoral instability. Fourteen articles met the inclusion criteria and were included in this review. The mean age of the patients was 24 years. The mean postoperative Tegner score was 5.7 and the pooled estimated mean postoperative Kujala score was 86. Eighty-four per cent of the patients returned to sports after surgery. The pooled total risk of recurrent instability after surgery was 1%, with a positive apprehension sign risk of 4% and a reoperation risk of 3%. The authors concluded that a high percentage of young patients return to sports after isolated MPFL reconstruction for chronic patellar instability, with short-term results demonstrating a low incidence of recurrent instability, postoperative apprehension, and reoperations.

Sherman and colleagues [143] evaluated the existing literature regarding return to play (RTP) and return to prior performance (RPP) following patellar stabilization surgery. These authors found that there is a lack of validation and universal adoption of standardized RTP guidelines. The best available studies to date would suggest high RTP rates (84–100%), average RPP rates (33–77%), and a highly variable timeframe (3 to 12 months) for return to sport. Sherman et al. [143] concluded that the best available data on RTP and RPP following patellofemoral instability is based on lower quality of evidence studies, expert opinion, and published societal guidelines.

Manjunath et al. [144] performed a systematic review to determine both the rate and timing of return to play after MPFL reconstruction, and the rate of further patellar instability. Their review found 27 studies including 1278 patients meeting the inclusion criteria. The majority of patients were women (58%), and the total group had a mean age of 22 years. The mean follow-up was 39 months. The overall rate of return to play was 85% (with 68% returning to the same level of play). The average time to return to play was 7 months postoperatively. The rate of recurrent instability events following reconstruction was 5%.

Platt et al. [145] undertook a systematic review and meta-analysis to evaluate return to sport after MPFL reconstruction for patellar instability. Twenty-three articles met the inclusion criteria after full-text review. A total of 930 patients were analyzed, including 786 athletes. The overall mean age of the patients was 21 years. Women represented 61% of all patients. The mean follow-up was 3 years (range, 0.8 to 8.5 years). The return to sport rate was 93%. Patients returned to or surpassed their preoperative level of activity in 71% of cases. An osteotomy was performed in 11% of the athletes. Return to sport did not differ significantly in

patients undergoing MPFL reconstruction without osteotomy versus those receiving additional osteotomy. Patients returned to sport at a mean of 6.7 months (range, 3 to 6 months) postoperatively. The overall complication rate was 9%. The most common complication was recurrence of instability.

We emphasize that the treating surgeon should counsel their patients preoperatively regarding their expectations and outcomes of treatment. Based on abovementioned studies, a high rate of return to sport after MPFL reconstruction surgery is expected. In our experience, most athletes return to play around 6 to 8 months after undergoing MPFL reconstruction.

#### **4.8 Complications of MPFL Reconstruction**

Postoperative complications following MPFL reconstruction include subcutaneous hematoma, wound infection, dehiscence, seroma after graft harvest, persistent pain, knee stiffness, flexion contracture, recurrent instability, patellar fracture, and deep vein thrombosis. The cause of recurrent patellar instability may be technically inadequate MPFL reconstruction or failure to address other concomitant pathology. Persistent pain may be caused by the over-constrained MPFL, unaddressed chondral defect in the patellofemoral compartment, or patellar fracture.

Shah and associates [146] performed a systematic review to determine the rate of complications associated with MPFL reconstruction. A total of 164 complications occurred in 629 knees (26%). These complications included wound infection, knee pain, restriction of knee flexion, recurrent patellar instability, and patellar fracture. Twenty-six patients returned to the operating room for additional procedures.

Parikh and colleagues [147] have reported the early complications (<3 years) of MPFL reconstruction in young patients. A total of 179 knees underwent MPFL reconstruction during the study period. There were 38 complications (16%) in 29 knees. The major complications included recurrent lateral patellar instability, knee motion stiffness with flexion deficits, patellar fractures, and patellofemoral arthrosis/pain. In their series, 18 of 38 (47%) complications were secondary to technical factors and were considered preventable. Female gender and bilateral MPFL reconstructions were risk factors associated with postoperative complications. Patients should be counseled preoperatively on the risk of potential complications that may occur after MPFL reconstruction.

Common fixation techniques for MPFL reconstruction at the patella include transosseous bone tunnels [148, 149], suture anchors [122, 150, 151], and interference screws [152–154]. It has been reported that the patellar tunnel techniques present a higher risk of postoperative patellar fractures, particularly for those that pass completely through the patella [146, 147, 155–159]. In view of the high risk of patellar fracture with the use of transosseous tunnel technique, the suture anchor fixation was introduced [154, 160]. Suture anchors provide a stable fixation and are gaining increasing popularity. Good to excellent results have been reported with the use of suture anchors for fixation of the tendon graft in MPFL reconstruction [122, 150].

#### **4.9 Authors' Preferred Treatment of MPFL Reconstruction**

In order to eliminate the risk of patellar fracture (that may occur using the patellar tunnel technique), the senior author of this paper (AJS), prefer to use suture anchors to fix the tendon graft to the medial border of the patella. Kurowicki et al. [130] have reported the Patella Footprint Technique of MPFL reconstruction. In our *Patellofemoral Instability DOI: http://dx.doi.org/10.5772/intechopen.99562*

opinion, this surgical technique provides a safe, reliable and reproducible method of restoring patellofemoral stability. The Patella Footprint Technique minimizes the stress risers in the patella by using suture anchor fixation that creates a ligamentous footprint instead of tendon healing into a bony socket in the patella.


*Article* **Impact of Three Different Processing Techniques on the Strength and Structure of Juvenile Ovine Pulmonary Homografts**

**Johannes J van den Heever 1,\* , Christiaan J Jordaan 1 , Angélique Lewies 1 , Jacqueline Goedhals 2 , Dreyer Bester 1 , Lezelle Botes 3 , Pascal M Dohmen 1,4 and Francis E Smit 1**

**Abstract:** Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on the strength and structure of ovine pulmonary homografts harvested 48 h post-mortem. Cells and cellular remnants were present for the cryopreserved group, while the decellularized groups were acellular. The decellularized group had large interfibrillar spaces in the extracellular matrix with uniform collagen distribution, while the additional fixation led to the collagen network becoming dense and compacted. The collagen of the cryopreserved group was collapsed and appeared disrupted and fractured. There were no significant differences in strength and elasticity between the groups. Compared to cryopreservation, decellularization without fixation can be considered an alternative processing technique to maintain a well-organized collagen matrix and tissue strength of homografts.

**Keywords:** homografts; ischaemic harvesting; decellularization; cryopreservation; glutaraldehyde-fixation


**STOCHASTIC MODELING AND CONTROL**

Edited by **Ivan Ganchev Ivanov**

#### **Stochastic Modeling and Control**

http://dx.doi.org/10.5772/2567 Edited by Ivan Ganchev Ivanov

#### **Contributors**

Josefa Linares-Perez, Raquel Caballero-Aguila, Irene García-Garrido, Ricardo Lopez-Ruiz, Ivan Ivanov, David Akinyiwola Opeyemi, Vladimir Prof. Simovic, Sinisa Fajt, Miljenko Krhen, Serena Doria, Jingtao Shi, Sergey Sokolov, Vyacheslav Vasiliev, Uwe Küchler, Nicholas A. Nechval, Raul Fierro, Tiong Wee Lim, Tze Leung Lai, Hui Zhang

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As mentioned earlier, doping in sports can create moral dissonance in athletes. They can apply moral neutralization techniques to overcome any initial moral misgivings about going down that path. Those who do can end up with a mind-set in which any traces of a bad conscience seem to have disappeared. The cyclist Tyler Hamilton was a member of Lance Armstrong's team. He wrote a book about his experiences in an environment in which doping and deceiving the doping controllers was an everyday occurrence. One quote illustrates the mind-set that enables normalization of questionable behavior:

I've always said that you could have hooked us up to the best lie detectors on the planet and asked us if we were cheating, and we'd have passed. Not because we were delusional—we knew we were breaking the rules—but because we didn't think of it as cheating. It felt fair to break the rules, because we knew others were too. (Hamilton & Coyle, 2012, p. 95)

It is not known whether Hamilton and his teammates ever experienced significant moral dissonance before engaging in doping. In this quote, any traces of moral doubt about competing under the influence of illegal performance-enhancing drugs have disappeared. Hamilton and the others felt that is was fair to break the rules.

This chapter showed that those in organizations who are responsible for (and concerned about) ethics should take heed of how (1) moral dissonance can disappear through processes of (2) moral neutralization, which can pave the way for a (3) normalization of questionable behavior. People can be familiar with the Navigation Wheel and the whole array of ethical theories, principles, and concepts and still be vulnerable to developments of this kind. Excellent analytical skills do not offer sufficient protection against becoming involved in neutralization processes. Maybe some individuals of firm and stable character are better equipped to resist invitations to use moral neutralization techniques than others. In an organization, the main countermeasure against the development from (1) through (2) to (3) is encouraging people to speak up and confront colleagues who appear to be engaged in moral neutralization.

To be the one providing resistance to a leader or a colleague's neutralization attempts takes courage and can be unpleasant. In many instances, people will interpret it as an unwanted disruption of a process that is in flow. Why spoil the path toward higher profits and better margins for the organization? When a person has been brave enough to voice his or her moral concerns in such a context, all eyes will be on that person for some time. Colleagues will be eager to see what happens next in that person's career. Was it a wise move or one that the person receives punishment for in the form of remaining on the same step on the career ladder or having to take steps down? The answer exposes the organization's communication climate for stopping moral neutralization in its tracks. The next and final chapter of this book discusses more broadly the organizational climate for addressing and discussing ethical issues at work.

#### References

Ariely, D. (2012). *The (honest) truth about dishonesty*. New York: Harper Collins.

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/ by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### The Invisible Gorilla

**Abstract** Concentration on a particular task can take away our ability to attend to important nuances of a situation. Aspects that are very vivid to outsiders can be invisible to the hard working and deeply absorbed insiders. This chapter argues that moral blindness in organizations can occur when people develop routine ways of looking at things and gradually fail to see moral aspects of their own conduct. They may also be blind to their own moral blindness. Workplace incentives have a significant impact on how employees see reality in their organizations, and can make moral dimensions of the activity become blurred and invisible. Generous bonuses can speed up moral neutralization and make initial misgivings about goals and methods at work disappear from view. Even people with excellent abilities in ethical analysis and with the most dependable and stable character traits are vulnerable in this respect. A crucial element in ethics in organizations should therefore be to establish communication climates that encourage people to speak up when they observe what appears to be morally dubious conduct in their own working environment.

**Keywords** Moral blindness • Aspect blindness • Moral muteness • Invisible gorilla

On a day when I was working on this book, I got a phone call from a woman who wanted me to contribute with a presentation on an ethics day in her organization. Her idea was to make leaders and employees in the organization familiar with the Navigation Wheel and other ethical tools and principles. I was willing to contribute, but had to check my calendar first. It turned out that I had an appointment for that particular day, to hold an ethics talk in another organization, so regrettably I had to say no to the invitation. When the woman heard this news, she hesitated for a brief moment, before she said: "What if we pay you a bit extra to come to us?" To my astonishment, she offered to pay me for breaking the promise of giving an ethics talk in one organization, in order to come and give an ethics talk in her workplace instead. I responded by asking her to think through that offer one more time, and consider whether she meant it seriously. It did not take her long to realize how inappropriate her suggestion was, particularly in the light of the topic of the seminar day. She had just been so eager to get the program for the day in place, with me as one of the contributors. For a moment, she had been blind to the moral aspect of the situation, and suggested something that she realized on second though was out of the question.

Moral blindness is something that can strike any decision-maker in an organization. People are engaged in absorbing and complex tasks and are supposed to deal with them quickly in order to be ready for further challenges at work. In the heat of the moment, they can become blind to important aspect of the situation. The perception psychologists Christopher Chabris and Daniel Simons have made a short film to illustrate how people's attention in a given situation is selective and vulnerable to manipulation (Simons & Chabris, 1999). The film shows six people, three of them in white clothes and three of them in black clothes, walking around in circles while they are passing basketballs to each other. Each team has one basketball, and the team members pass it among each other while they are constantly on the move.

The assignment to the film's audience is to count the number of times the team wearing white manages to pass the basketball to each other. Those who really concentrate on the task come up with the correct answer, which is 15. A facilitator then asks if they noticed anything else during the film. Some report that they have glimpsed a black figure walking across the screen. To check this observation, the film runs one more time, and on this occasion, everybody can see the big gorilla figure walking slowly into the frame, stopping in the middle of it, banging its chest, and then moving slowly out of the picture. The gorilla takes up a lot of space, and the people who are blind to it on the first showing find it hard to believe that it can be the same film. Those who fail to spot the gorilla the first time around are typically very surprised by their inability to do so, and this has led Kahneman (2013) to reflect that they are not only aspect blind, but also blind to that particular blindness. The gorilla experiment challenges the assumption that all people need to do in order to figure out what is happening in a particular part of their surroundings, is to turn their faces in that direction and take a look.

The invisible gorilla can function as a symbol of the significant aspects of people's own working environment that they can be blind to during their efforts to perform complex tasks with a tight time schedule. Some of these aspects can be morally significant. People can be morally blind due to the complexity of the situation and the demands that are put on them, and also as a result of economic and other incentives. Bird (1996, p. 85) defined moral blindness in the following way: "People are morally blind when they fail to see or recognize moral concerns and expectations that bear upon their activities and involvements."

Moral blindness is a different form of blindness from the one mentioned in first chapter of this book, where the decision-maker deliberately adopts the position of willful blindness, deciding to turn a blind eye to the case at hand, not wanting to know details. Gorilla blindness occurs involuntarily, as a result of our limited perception capacities. Conflict of interest issues can typically become invisible to professionals, when high personal ambitions can make self-interest overshadow client interest. Airely's physician, mentioned in Chap. 11, appears to have become morally blind in this manner, in his efforts to recruit the third patient he needed in order to move forward with an academic paper. Financial advisors in many countries appeared to lose sight of client interest prior to the financial crisis, making it possible for them to recommend and sell questionable products, without experiencing moral dissonance. Moral blindness can occur in any organization, including institutions where people research and teach on the topic of ethics in organizations. In line with Kahneman's remark that people are blind to their own aspect blindness, it may also be that leaders and employees in organizations are blind to moral aspects of what they are doing at work, and also blind to that particular blindness.

One of the paths to moral blindness goes through the process of moral neutralization, where the decision-maker convinces himself or herself to leave behind initial moral misgivings about a particular option. Once a person or an environment has crossed that hurdle, it seems difficult to return to the state where the option in question seemed morally dubious. The moral aspects we could see from the old perspective are now invisible, like the gorilla in the film. As noted in the previous chapter, Hamilton and Coyle (2012) have described how individuals in a tight and loyal collective like the cycling team of Lance Armstrong, can strengthen each other's firm beliefs that their cheating behavior is beyond reasonable reproach.

Organizations that are serious about ethics depend on a communication climate where the normal response when an employee has moral doubts about a particular course of action, is for him or her to speak up and address the issue. When deciding to voice a moral concern, the employee should ideally not experience fear over what comes next in terms of possible negative sanctions from colleagues and leadership. Moral muteness (Bird, 1996) can be a feature in organizations where people are afraid to speak their minds on moral matters: "Many people hold moral convictions yet fail to verbalize them. They remain silent out of deference to the judgments of others, out of fear that their comments will be ignored, or out of uncertainty that what they might have to say is really not that important" (Bird, 1996, p. 1). Individuals in organization can have the impression that they are alone in having moral misgivings about how their workplace operates. They can be unaware that colleagues in the same unit actually share their moral concerns, since they never raise the issue and address the topic collectively.

It is in this context that the category of relational moral luck, briefly introduced in Chap. 4, makes good sense. A decision-maker can be fortunate or unfortunate with the people who are in the social surroundings at the crucial moment when he or she is about to respond to a moral dilemma—whether it be a real or false one. That particular social environment can be one where people normally challenge and support each other critically in such situations, or one where nobody lifts an eyelid when a colleague enters into morally questionable territory. It is not merely due to luck whether you are in one or the other of these kinds of surroundings, as we do make decisions about the kind of organization we want to work in and belong to. However, the communication climate of the workplace might be something that we only gradually become aware of, and coincidences and luck can play a part in deciding whether we end up with colleagues who care enough to intervene, or not.

Two phenomena identified in social psychology highlight how crucial it can be to establish a constructive communication climate in organizations. They are relevant for judgment and decision-making in the workplace beyond ethics. *Confirmation bias* is the tendency we have to notice and seek information that confirms our beliefs, and to be inattentive to information that provides us with reasons to change our beliefs. The phenomenon is well documented in research (Nickerson, 1998), and produces formidable challenges in many professions. Police investigators can make up their minds about which person has committed a crime, and only pursue and notice information that confirms that conclusion. Teachers can have preconceptions about the intelligence and abilities of their pupils, and fail to see upward and downward spirals in their developments. Researchers can be so satisfied with their hypotheses and explanations of phenomena that they become blind to glaring counterevidence and reasons to revise them. In these and other professions, knowledge about confirmation bias is part of the professional training. This is nevertheless a pervasive decision-making trap, and one that emphasizes the need to have communication climates where colleagues look out for each other and intervene when someone at work stubbornly holds on to one belief or viewpoint rather than revises it in the light of new and relevant information.

The other psychological phenomenon that can slow down a process of identifying and addressing morally relevant aspects of behavior in an organization is *the bystander effect*. Research on human behavior in real situations and in experiments show that the greater the number of bystanders to an event where somebody needs help, the less likely is it that any one of them will actually help (Darley & Latané, 1968; Greitemeyer & Mügge, 2015; Latané & Darley, 1976). One cause for this effect seems to be what Darley and Latané (1968) called diffusion of responsibility. People consider their responsibility to help in a situation to be one unit that they share evenly with the other people at the scene. If they are one hundred bystanders to a critical situation, they seem unconsciously to split responsibility into one hundred tiny pieces, leaving each of them with one hundredth of a responsibility to intervene and help. That is a very small piece of responsibility for one individual, who can turn his or her back to the situation, without experiencing bad conscience. If there instead are 50 bystanders, the responsibility is double that of in the previous situation, but one fiftieth of a responsibility is still very little. This way of thinking is what Parfit (1984) labeled mistakes in moral mathematics. People do have individual responsibilities to help, no matter how many others are present. It is unreasonable to consider responsibility to be one cake people share evenly in thin slices. Each individual has his or her own cake of responsibility.

Another cause for the bystander effect is pluralistic ignorance, or the fact that each of us tend to interpret the inactivity of the others as a sign that nothing serious is going on, and that there is no reason to engage (Darley & Latané, 1968). From my perspective, it looks like the man is hurt and needs help, but nobody else in the crowd appears to think so. My initial judgment of the situation appears to be wrong, since everybody else is passive. I might be too sensitive in my interpretation, overdramatizing the situation in my head. It looks like a gorilla, but nobody else shows any sign of seeing it, so perhaps it is an illusion. The strength of this tendency to doubt one's own evaluations tends to be proportionate to the number of bystanders.

The bystander effect is relevant for ethics in organizations in that the number of people who perceive that there is something morally wrong with the setup of a particular project, with the relationships with the suppliers, or with the new products or sales methods, affects the likelihood that anybody will take initiatives to be critical of them (Beu, Buckley, & Harvey, 2000; Zhu & Westphal, 2011). Even here, it is probable that the higher the number of bystanders, the lower the likelihood of an intervention. It may be that knowledge about the bystander effect can weaken it, as suggested by Mele and Shepherd (2013). It is thus worthwhile to make leaders and employees in organizations aware of it, for reasons that go beyond ethics. It is also possible to counter the effect by delegating responsibility to particular individuals. If you need help and are surrounded by bystanders, you should point to one person and ask for help, rather than shout for help in the general direction of everyone. Addressing one person directly with a call for help has the positive double effect of both (1) disrupting the mistake in moral mathematics of splitting responsibility up in tiny pieces, and of (2) avoiding pluralistic ignorance, or the misperception that everything is as it should be.

Maria Gentile has developed the concept of Giving Voice to Values (GVV) as a method for individuals at work to stand up for their moral beliefs and values, even when they are under pressure from colleagues, leaders, customers, and other stakeholders not to do so (Gentile, 2010, 2012). GVV has generated considerable research interest (Edwards & Kirkham, 2014; Gonzalez-Padron, Ferrell, Ferrell, & Smith, 2012) and also inspired practitioners in organizations. It encourages people to overcome moral muteness and speak their minds when they observe decisionmaking and conduct that goes against their moral values. It also provides concrete action plans and scripts for people who want to become better at giving voice to their values at work. In many ways, GVV seems designed to address the needs identified in this book, to intervene when colleagues engage in moral neutralization and gradually become blind to moral aspects of their own behavior.

There is much to commend and admire in Gentile's approach, but it is problematic in one important respect. The subtitle of the GVV book is "How to speak your mind when you know what's right" and the tone of actually knowing what is right is prevalent in the text. Gentile offers practical advice to individuals who clearly see how things stand, and what it will mean to stand up for one's values in the situation, and need to go from conviction to enactment. Research on the bystander effect and similar phenomena indicate that people are often in situations where they do not know what is right, but have doubts about how to interpret what is enfolding in front of them. They somehow need to give voice to that doubt, and not remain passive. The starting position of being a person who knows full well what is right and true does not invite dialogue or attention to how other people see the situation. It is not the position of listening to other perspectives and being open to revise one's beliefs and assumptions.

The label for an alternative approach can be to give voice to doubt rather than to value. Uncertainty and doubt appears to be a more realistic and constructive starting point for conversations about right and wrong than one where people have made up their minds in advance. One frame of reference can be that of Socratic dialogue, where the aim is to engage in inquiry and questioning in order to reach consensus on an issue. Brinkmann, Lindemann, and Sims (2016) have suggested a design inspired by the idea of Socratic dialogue, where people engage in collaborative search for truth regarding a particular normative question. In essence, the Socratic design invites respect for the myriad of perspectives that deserve a hearing when people try to reach a common understanding of how to act in a particular situation.

The aim of this book has been to suggest ways to rethink and restructure ethics in organizations. Decision-makers in organizations, both leaders and employees, face moral dilemmas where they need to give appropriate weight to legal, ethical, moral, reputational, economic, and value based aspects of the situation. They cannot rely solely on moral intuition or gut feeling—Kahneman's System 1 thinking—but also need to be able to analyze the situation carefully—Kahneman's System 2 thinking. The combination of good analytical skills and stable character can make an individual well equipped to meet moral dilemmas, but studies in behavioral economics, social psychology, and criminology show that more or less anybody can become entangled in moral wrongdoing, depending on the circumstances. In organizations, people depend upon colleagues to intervene and stop them when ambition and other factors tempt them to take moral shortcuts. It can be enough that they raise doubts about the path colleagues are contemplating, since that gives them reasons to rethink and reconsider. Ethics in organizations can build on a rich array of research and knowledge, from well beyond the traditional sources of moral philosophy. Doing so can make the workplaces less vulnerable to the unpredictable and erratic activities of invisible gorillas.

#### References

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/ by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.


**4. Remote sensing of biomass in miombo woodlands: Opportunities and limitations for research**

Miombo display complex vegetation patterns in which dense vegetation alternates with sparsely populated or bare soil in response to environmental and disturbance (deforestation, fires and herbivory) factors. Low vegetation cover, in some places, and small-scale variations in others, can produce unpredictable errors in the quantication of biophysical and ecological properties of the vegetation. Ignoring this spatial variation can produce inaccurate results, even in fairly homogeneous environments (Aubry & Debouzie, 2001 cited by Hufkens *et al.,* 2008; Haining, 1990).

The use of remote sensing for estimations of vegetation biomass has proved to be of great importance to fill up data gaps and to estimate large-scale variations, especially in low accessible places. The technique lacks of precision when compared to detailed forest inventories. But, for miombo the lack of detailed field data and uncertainty of biomass stocks associated to disturbances, make remote sensing one important technique to address temporal and spatial variations in biomass.

Although repeated satellite imaging has improved in resolution over the years, it is still limited in detecting fine patterns within savanna vegetation. Some forms of remote sensing, such as the sub-meter resolution IKONOS, GeoEye and QUICKBIRD satellite sensors, allow individual trees to be recognized. Other, such as microwave remote sensing from radar (RADARSAT, ALOS-PALSAR, JERS-1, etc.) and LiDAR provide a three dimensional representation of vegetation, which is an improvement over optical remote sensing. However, both low-resolution optical and microwave scenes are currently too expensive for large-scale or regional studies and they require a substantive amount of processing capacities. These represent some of the major limitations for its use in the southern Africa region.

Discriminating between subtypes of savanna vegetation, even simply looking at structural differences, has proved a taxing undertaking, especially in places where field data is limited.

Remote Sensing of Biomass in

are:

change.

**6. References**

the Miombo Woodlands of Southern Africa: Opportunities and Limitations for Research 93

2. There exist few sites in the region with detailed data on biomass variations that can be used to test improved remote sensing techniques. For example, permanent sample plots exist in almost all miombo countries. These plots are being frequently evaluated for

several parameters including biomass and carbon in different compartments; 3. There are a growing number of remote sensing specialists in the region. In addition, several networks (miombo network, safnet, saccnet, among others) are dedicated to improve remote sensing techniques and data sharing. These involve not only regional but also international senior specialists thus representing a good way of data sharing,

improve techniques, establish a link between research and decision making, etc. In face of the limitations and opportunities for the remote sensing of biomass in miombo, there are five research areas of interest in the region that can benefit from the advance of remote sensing techniques. The core areas presented below are general and can accommodate several research topics according to site particularities. The research themes

1. Land use and land cover changes and its effects on miombo biodiversity and biomass; 2. Improved techniques for spatial and temporal variations of biomass and biodiversity; 3. Contribution of miombo to the global changes. This may include several topics such as: carbon stock assessment for different ecosystem compartments (vegetation, soils, NPV, belowground); fire regimes and management; vulnerability and adaptation to climate

4. Biomass changes and effects on the availability of resources to human population;

Anaya, J.A.; Chuvieco, E. & Palacios-Orueta, A. (2009). Aboveground biomass assessment in

Andreae, M.O. (1993). The influence of tropical biomass burning on climate and the

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Asner, G.P.; Knapp, D.E.; Cooper, A.N.; Bustamante, M.M.C. & Olander, L.P. (2005).

Backéus, I.; Petterson, B.; Strömquist, L. & Ruffo, C. (2006). Tree communities and structural

Banda, T.; Schwartz, M.W. & Caro, T. (2006). Woody vegetation structure and composition

Colombia: A remote sensing approach. *Forest Ecology and Management,* Vol.257,

atmospheric environment, In: *Biogeochemistry of Global Change: Radiatively Active Trace Gases,* Oremland, R.S., (ed.), 113-150, Chapman & Hall, New York, NY, USA.

structure and function from imaging spectrometry and inverse modeling. *Ecological*

signatures in arid and semi-arid ecosystems In: *Remote Sensing for Natural Resources Management and Environmental Monitoring,* Ustin, S.L, (ed.), 53-109, John Wiley and

Ecosystem Structure throughout the Brazilian Amazon for Landsat Observationsand Auntomated Spectral Unmixing. *Earth Interactions*, Vol.9, pp.1-30

dynamics in miombo (*Brachystegia*\_*Julbernardia*) woodland, Tanzania. *Forest Ecology*

along a protection gradient in a miombo ecosystem of western Tanzania. *Forest*

5. Knowledge Management: from science to policy.

*Applications,* vol.8, pp.926-941

Sons, Hoboken, New Jersey, USA

*and Management,* Vol.230, pp. 171-178

*Ecology and Management*, Vol.230, pp.179-185

pp.1237–1246. doi:10.1016/j.foreco.2008.11.016

Thus, there is a pressing need to intensify studies calibrating satellite with field measurements, albeit the low accessibility of some areas in the miombo ecoregion. In addition to spatial measurement, it has long been clear that temporal surveys at varied time intervals are required, particularly in biomes that are highly dynamic such as miombo (Furley, 2010).

The problem of biomass retrieval in miombo is compounded by the fact that senescent and dead material (also known as NPV) associated with phenology and disturbances can be a major component of the total surface cover. These three factors play a major role in both abiotic and biotic dynamics of the miombo as explored in Section 2 of this chapter. NPV can represent an important carbon pool in this ecosystem. Many common methods for estimating vegetation cover and biomass use VIs that are insensitive to the presence of NPV. Thus, SMA, data fusion among others may be more appropriate techniques to address spatial and temporal variations of biomass in miombo, but they still need to be adapted and calibrated for this ecosystem.

Addressing large-scale and temporal variations of biomass in the different compartments of miombo (PV, NPV, soils and underground) has to be enhanced in the near future due to their varied contribution to global emissions of greenhouse gases - Carbon dioxide in particular. For example, NPV is the main source of fuel-load for fires, which causes large amounts of carbon to be lost in the form of carbon dioxide to the atmosphere. Because of this, the contribution of miombo to global climate changes may be significant but not completely understood yet.

The southern African region is embarking in the carbon market under the Kyoto Protocol and REDD schemes of the UNFCCC. The ability to negotiate in this market and gain a better position is dependent on the capacity of a country (or region) to estimate carbon stocks with minimal errors. Thus, the advance of remote sensing measurements of biomass from space is an important step towards that achievement (Houghton, 2005 cited by Houghton, 2010). However, it is important to acknowledge that most remote sensing techniques for measurements of biomass usually miss belowground biomass and soil carbon in tropical and sub-tropical regions, which may hold a representative fraction of carbon in the whole system. Thus, future research should focus on the use of microwave radar remote sensing (P-Band and higher) or optical techniques such as SMA and data fusion, that are able to differentiate carbon pools.


**4. Conclusions**

Monogenic causes of nephrocalcinosis account for a rare set of conditions with a low population frequency. However, the clinical course for affected patients is very different depending on their underlying genotype. Accurate, prompt diagnosis allows early initiation of conservative measures, which in some cases can halt nephrocalcinosis or delay progression of renal impairment. Establishing the underlying genetic mutation also allows accurate prognostic information to be given and can help facilitate screening of other family members. As our understanding of these rare inherited conditions increases, it is hoped further treatment targets that address underlying enzymatic/protein defects will emerge. However, at present for the majority of cases treatment strategies focus upon supportive treatments to correct biochemical parameters, and careful monitoring of disease progression.

**Funding:** This research received no external funding. **Conflicts of Interest:** The authors declare no conflict of interest.

1ESRD = End stage renal disease, 2 HCINF1 = Hypercalcemia, idiopathic, of infancy type 1, 3 AR = Autosomal Recessive, 4 HCINF2 = Hypercalcaemia, idiopathic, of infancy type 2, 5 FHHNC = Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, 6 CKD = Chronic kidney disease, 7 BSND = Bartter Syndrome, Neonatal, with Sensorineural Deafness, 8 AD = Autosomal Dominant, 9 Distal RTA = distal renal tubular acidosis.


The Molecular Basis for Radioiodine Therapy

*Gerardo Hernán Carro and Juan Pablo Nicola*

### **Abstract**

Radioactive iodine (radioiodine) therapy is a standard and effective therapeutic approach for high-risk differentiated thyroid carcinomas, based on the unique ability of the thyroid follicular cell to accumulate iodide through the sodium/iodide symporter (NIS). However, a recurrent limitation of radioiodine therapy is the development of radioiodine-refractory differentiated thyroid carcinomas, which are associated with a worse prognosis. Loss of radioiodine accumulation in thyroid carcinomas has been attributed to cell dedifferentiation, resulting in reduced NIS expression and NIS intracellular retention involving transcriptional and posttranscriptional or posttranslational mechanisms, respectively. Emerging therapies targeting the oncogene-activated signal pathways potentially involved in thyroid carcinogenesis have been able to recover radioiodine accumulation in radioiodine-refractory tumors, which constitutes the rationale of redifferentiation therapies. Here, we will comprehensively discuss the molecular mechanisms underlying radioiodine therapy, refractoriness to radioiodine therapy in differentiated thyroid carcinomas, and novel strategies for restoring radioiodine accumulation in radioiodine-refractory thyroid carcinomas.

**Keywords:** differentiated thyroid cancer, sodium/iodide symporter, radioiodine therapy, radioiodine-refractory thyroid cancer, redifferentiation therapy

### **1. Introduction**

The ability of the thyroid follicular cell to accumulate iodide constitutes the cornerstone for diagnostic scintigraphy and therapy for hyperfunctioning thyroid tissue, as well as for differentiated thyroid carcinoma and their metastases after thyroidectomy [1]. Radioactive iodine (radioiodine) administration used in thyroid tissue remnant ablation after thyroidectomy and adjuvant therapy in metastatic differentiated thyroid carcinomas has been possibly the most successful internal radiation therapy ever designed. In patients with high-risk differentiated thyroid carcinomas, retrospective studies have demonstrated that the ability of tumor cells to accumulate radioiodine is the best indicator of disease-free and of overall survival [2].

Currently, thyroid hormone withdrawal and recombinant thyrotropin-stimulated radioiodine adjuvant therapy are considered in intermediate-risk carcinomas and are routinely recommended for high-risk differentiated thyroid carcinomas after total thyroidectomy [3]. However, differentiated thyroid tumors often exhibit reduced

(or even undetectable) radioiodine accumulation, compared with normal thyroid tissue, and are diagnosed as cold nodules using thyroid scintigraphy. Despite this reduction, over 70% of differentiated thyroid carcinomas accumulate radioiodine to some extent, which is still sufficient to achieve adequate radioiodine accumulation for treatment. Unfortunately, 30% of metastatic differentiated thyroid tumors completely lose their ability to accumulate iodide, with this percentage increasing up to 70% when the oncogene BRAFV600E is present. This causes thyroid tumors to become refractory to radioiodine therapy and is associated with a poor outcome. Patients with thyroid cancer metastases that accumulate iodide show a survival rate at 10 years of ~60%, while survival is drastically reduced to ~10% in patients with radioiodine refractory metastases [4]. Therefore, a better understanding of the biological mechanisms leading to differentiated thyroid carcinoma resistance to radioiodine therapy will certainly have major implications for its treatment [5].

The clinical experience of radioiodine theranostic in the management of differentiated thyroid cancer has opened up a complete new field related to developing strategies to extend this promising approach to non-thyroidal cancers. Although, in addition to thyroid cancer, functional endogenous radioiodine accumulation has only been observed in breast and ovarian cancer [6, 7], this could be key for radioiodine being used as an effective therapeutic tool. The ectopic induction of radioiodine accumulation using gene transfer has paved the way for the development of new therapeutic strategies to treat tumors with radioiodine, as in differentiated thyroid cancer. Since a pioneering study successfully induced iodide accumulation in malignant transformed thyroid cells that did not accumulate iodide, thereby rendering them sensitive to radioiodine treatment [8], a large body of evidence has shown the feasibility of inducing radioiodine accumulation in several cancer cell lines [9, 10].


*3.3. Revisions*

Revision surgery was required for 7 patients (6%) including 2 HA (2%) and 5 TSA (26%) (OR = 20; (95% CI = 4–116); *p* < 0.001). Survival rate without revision at 5 years was 97% (89–99%) for HA and 97% (89–99%) for TSA. At 10 years, survival rate without revision was 95% (68–99%) for HA and 57% (19–82%) for TSA (*p* < 0.001) (Figure 1).

**Figure 1.** Survival curve of HA and TSA after PANHH.

In the HA group, 2 were revised for glenoid wear. The stage of Ficat's classification in pre-operative radiographs was stage 3. The first one was a resurfacing HA (Figure 2) complicated with painful glenoid wear at 49 months and reoperated with a pyrocarbone HA. During the final FU, 2 years after the revision surgery, the Constant score was 55 and SSV 80%.

**Figure 2.** Resurfacing complicated by glenoid wear at 49 months of FU.

The second case was a metal HA where glenoid wear occurred at 25 months of FU (Figure 3). The humeral stem was unchanged and a cemented full PE glenoid was implanted. During the final FU, 3 years after the revision surgery, the Constant score was 57 and SSV 70%.

**Figure 3.** HA metal complicated by glenoid wear at 25 months of FU.

In the TSA group, one patient who had a posterior instability underwent a full-PE implant but due to a glenoid loosening 5 years later, it lead to a definitive explanation of both humeral and glenoid components with a poor functional result (CS = 15). Three patients with glenoid loosening were reoperated using HA (Figure 4).

**Figure 4.** (**a**) TSA complication due to glenoid loosening at 9 years FU and (**b**) reoperated using an HA.


**2.1 Glycogen synthesis**

Two enzymes, glycogen synthase and glycogen phosphorylase, control glycogen levels. Both enzymes are regulated by phosphorylation and allosteric modulators. Specifically in the fed state, insulin activates glycogen synthase (limiting enzyme for glycogen synthesis) by promoting its dephosphorylation and, at the same time inhibits glycogen phosphorylase (important for glycogen breakdown). Meanwhile, glucose-6-phosphate binding to glycogen synthase favours its dephosphorylation, promoting glycogen synthase activity (Bollen, 1998; Agius, 2008). As a result, glucose coming from bloodstream fills hepatic glycogen stores.


*5.1.2 Multi-effect distillation (MED)*

One of the oldest industrial desalination processes that are used today is Multieffect distillation (MED) [87, 88]. The MED evaporator consists of cells, called effects, decreasing pressure and temperature from first to last, with temperature typically between 65 and 90°C [89]. Each effect consists of evaporator tube bundles on which seawater is sprayed. Heating steam or hot water through the tubes is supplied in the first effect and it transfers energy to the seawater in each effect, causing partial evaporation [90]. In each effect, the low pressure and temperatures affect the boiling point of water and with decreases of its, water becomes evaporate [88]. By using a heat exchanger and condensing the steam, clean distillate water is produced. This product water is pumped into a storage tank while the brine is pumped back into the sea.

For the production of water in a MED plant with a capacity range between 5000 and 50,000 m3 /day, we require thermal energy between 145 and 230 MJ/m3 , which will be equal to 12.2–19.1 kWh/m3 of electrical energy. Furthermore, for pumps consumption will have been needed 2–2.5 kWh/m3 of additional electrical energy [91]. Vapor flow and feed configurations are two major parameters that can effect on energy consumption in the MED process.

#### *5.1.3 Electrodialysis (ED)*

Electrodialysis (ED) is an electro membrane process in which with use of an electric field ionic and non-ionic components are removed [29]. In these kinds of processes, Anions and cations migrate towards the positive and negative electrode, respectively, and so the separation process happens. As can be show in the **Figure 10**, an ED system consists of alternately arranged anion exchange membranes (AEM) and cation exchange membranes (CEM).

The energy consumption in ED strongly depends to the salt concentration in feed solution. The rate of salt removal is proportional to the electric current [80, 92]. In order to efficient separation of ions from feed solution with high concentration, would require a high potential difference, thus, the use of ED process for seawater desalination, due to high concentration of ions in seawater and the need for high energy consumption, it is not affordable. This process is suitable for solutions with low-concentration of TDS (<5000 mg/L) such as brackish water [93]. Other parts that consume energy is the pumping unit and electrodes. On the basis of recent study, about 1–3% of the total energy consumption is related to these sections [92, 94].

Theoretically, in ED, for producing water with TDS about 800 mg/L the requirement of energy is 3.3 kWh/m3 and 26 kWh/m3 for desalination of brackish water and seawater, respectively [95]. On average, 0.7 kWh for each 1000 mg/L

**Figure 10.** *Schematic of electrodialysis desalination.*

### *Energy Recovery in Membrane Process DOI: http://dx.doi.org/10.5772/intechopen.101778*

TDS removed, 0.5–1.1 kWh/m3 for pumping, and roughly 5% accounts for energy losses in a brackish water ED desalination system [96]. In a study that was reviewed by Sajtar and Bagley, they found in order to removal of TDS up to 2000 mg/L in feed stream, the energy consumption is ranges from 0.1 to 1 kWh/m3 [92, 94]. Although ED is typically applied as a room temperature process, introducing a temperature gradient or increasing the temperature of the system can cause energy reductions [94]. Benneker et al. [97] found that the energy required for ED can be reduced by 9% if the temperature of one of the feed streams is increased by 20°C. Increasing the temperature increases ion mobility, reduces electrical resistance of the solution and decreases solution viscosity.

On the basis of the water salinity, the consumption of the electrical energy by an ED system can be about 0.5–10 kWh/m3 [98]. For example, to lower TDS from 1500 ppm to 500 ppm, an ED unit would consume 1.5 kWh/m3 . Due to high energy consumption in ED systems, in order to management and reduced the energy consumption, Recently, multi-stage electrodialysis systems have been investigated. Chehayeb et al. [99] found that by using a two-stage system for brackish water desalination the energy consumption can be reduced up to 29%, that, this can reduce the fixed costs. The application of ED remains limited by the high cost of ion exchange membranes and electrodes, and the electrically-driven degradation of polymeric membranes [100].

### *5.1.4 Membrane distillation (MD)*

Membrane distillation is one kind of separation process which in it, a porous membrane with hydrophobic properties is in contact with aqueous heated feed solution on one side. In MD process, the membranes that was use it works like this, that inhibit from the passage of the liquid water, but on the contrary allowing permeability for free water molecules and thus, for water vapor. These membranes are made of hydrophobic synthetic material (e.g. PTFE, PVDF or PP) and offer pores with a standard diameter between 0.1 and 0.5 μm (3.9 106 and 1.97 105 in) [80, 101].

Due to the high amount of energy consumption and as a result the high cost of water production, MD has not still achieved widespread commercial implementation in desalination. There are four basic MD configurations included [102, 103];

In several studies it has been reported that both AGMD and VMD have greater thermal energy efficiency compared to other configurations, which makes them more popular choices for companies seeking to commercialize MD processes. In **Table 7**, the SEC values for several selected MD systems have been reported [102, 116–118].

## *5.1.5 Forward osmosis*

One kind of osmotic process is called forward osmosis (FO) that, in this process, like RO, in order to the separation of water from dissolved solutes, uses a semipermeable membrane. This process for creating the driving force for separation uses the osmotic pressure gradient, such that a "draw" solution of high

#### **Table 7.**

*Specific energy consumption (SEC) of selected MD systems [80].*

concentration is used to induce a net flow of water through the membrane into the draw solution, thus effectively separating the feed water from its solutes [80, 119]. As a result, separation in FO requires little or no hydraulic pressure as a concentrated draw solution (DS) with a greater osmotic pressure draws in water molecules from the feed solution through a membrane [120].

FO is widely promoted as a low-energy desalination technique. For the determination of the energy consumption in these kinds of plants, a DS recovery step is

#### *Energy Recovery in Membrane Process DOI: http://dx.doi.org/10.5772/intechopen.101778*

used. During the osmosis step, in order to overcome dropping the pressure in the feed channel, at 50% water recovery, a low-pressure pump is needed, and the energy consumed is equal to 0.10–0.11 kWh/m3 [25, 121]. For the osmosis step the values of 0.2–0.55 kWh/m3 have also been reported [122]. Moon and Lee suggest, in a FO desalination plant, for solute regeneration, the energy consumption range is from 3 to 8 kWh/m3 [123].


*2.1. Participants*

Power analysis indicated that a minimum of 6 gymnasts should be included in the study in order to detect an e ffect size (ES) of 0.78, obtained from the meta-analysis of Moran et al. [18] for girls younger than 15 years of age (within–between analysis of variance power = 0.80, alpha = 0.05, correlation between repeated measures *r* = 0.5; G-Power <IP_ADDRESS>).

Twenty-six female "Gymnastics for All" gymnasts, aged 13 ± 2 years were recruited from one gymnastics club. Criteria for inclusion were: regular training (i.e., three times per week for 90 min per session) for at least two years under the same coach; no involvement in any systematic strength and power training; competitive experience of at least one year. Participants were excluded if they had any musculoskeletal injury in the last six months or if they missed >10% of the training sessions. Gymnasts were randomly allocated (allocation ratio 1:1) to a training group (TG) and a control group (CG). Three athletes (two from the training group and one from the control group) were excluded from the study because they did not complete all tests. The final number of participants along with their anthropometric and maturity characteristics are presented in Table 1. The maturity o ffset was estimated according to the prediction equation of Mirwald et al. [35]. Before the start of the study, researchers informed coaches, athletes, and their parents about the purpose and risks of the study, and an informed consent was signed by the athletes and the participants' parents. All procedures were approved by the local university ethics committee (reference number: 115/10-04-2019) in compliance with the Code of Ethics of the World Medical Association (Helsinki declaration of 1964, as revised in 2013).

**Table 1.** Characteristics of the participants in the training group (TG) and the control group (CG) (mean ± SD).

### *2.2. Study Design*

A repeated-measures parallel group design was used in the present study. The same battery of tests was evaluated in both groups at the beginning and at the end of the intervention (10 weeks). Athletes in the TG performed a circuit-type strength and power training program (duration: 7–9 min) for 10 weeks in addition to their regular gymnastics training. The study took place in the pre-season period (from October to December). The following tests were repeated at baseline and after 10 weeks of training: 10 m linear sprint speed, one-leg (one-leg CMJ) and two-legs countermovement jump (CMJ), drop jump (DJ), single-leg jumping agility test (JA), and 10 consecutive repetitions of a sport-specific skill (round-o ff). All measurements were performed in the same testing session, 48 h after the last training. A standardized warm-up preceded testing that included 6 min of light jogging, dynamic stretching for the major muscle groups, and 2 short accelerations.

Twenty-six sessions of this circuit strength and power training program were performed on non-consecutive days (Monday, Wednesday, and Friday), at the end of regular gymnastics training. Four familiarization sessions were performed over a two-week period, before baseline testing, to get participants habituated to the circuit strength-power training and the testing procedures. Both training and control groups participated in all familiarization sessions. During that period, data were collected

to calculate intraclass correlation coefficients (ICCs) for each test, using a two-way mixed-model analysis of variance (ANOVA).


**Abstract**

Within the multimodal treatment, the extent of surgery for early-stage breast cancer treatment may be safely de-escalated. This strategy is associated with less morbidity, therefore significant improvements in quality of life (QoL). Nevertheless, conventional, ablative-only breast conservative surgery (BCS) has several limitations considering breast aesthetics and may impact QoL just opposite than anticipated. The concept of oncoplastic breast conservation emerged at the end of the last century intending to overcome these limitations. Although the primary goal remains oncological safe cancer resection, the enhanced aesthetic outcomes, achieved with this approach, significantly contribute to higher patient satisfaction. The author believes that mastectomy should no longer be offered as an equivalent treatment option for early-stage breast cancer patients with low-volume breast disease, irrespective of the availability of postmastectomy breast reconstruction. Moreover, with the opportunities of oncoplastic breast conservative surgery, the technical feasibility of breast conservation should not represent an issue even in a higher stage of the disease. Clinical decision on the type of oncoplastic procedure is mainly based upon the anticipated percentage of breast volume loss and the residual breast volume, as well as the availability of additional donor sites, patients' preference, and surgeons' skills.

**Keywords:** breast cancer, surgery, mastectomy, breast conservation, oncoplastic, quality of life


**3. Rural areas of EU member states in Central and Eastern Europe**

The rural area represent the entire territory positioned outside large urban areas comprising small settlements whose inhabitants have an occupancy rate in agriculture, forestry, industry or other branches of rural economy. Development of rural areas is a priority in EU policy because rural areas represent more than 80% of the surface and comprises over 50% of the total population. Due to different levels of development among member countries there is a significant gap between western rural spaces and rural areas of the new member states from Central and Eastern Europe, where the main activity that occupies a large part of the popula‐ tion is agriculture, forestry and manufacturing of raw materials resulting from these domains. Within the EU there is common agricultural policy (CAP), which represents the framework according to which all activities from the primary sector are driven in the European rural economy. Since 1962, when it was launched, the CAP has been a partnership between agri‐ culture and society that has as the following objectives:

European agriculture supported through the CAP must provide an increasing production of basic foods as a result of continuous population increase. It also takes into account the sustainable management of natural resources, supporting continuous development of European rural areas and rural economy.

As a direct aid through CAP, three main directions can be defined as follows:

the Czech Republic and Bulgaria are close or even exceed the 80% of the GDP value. Also, using an important macroeconomic indicator, represented by gross national income (GNI), information can be obtained regarding the total income earned by residents of analysed countries and based on the obtained values a comparison can be accomplished regarding the purchasing power with direct implications for living standards in a particular country. Thus, GNI per inhabitant for the Eastern European countries was calculated, EU Members, for the period 2000–2009 and the results are shown in Figure 7. Visible differences between countries depending on the economy level of development can be observed, but the trend is upward for all 11 analysed countries since 2000, continuing with the EU accession years 2004 and 2007 and

Proceedings of the International Conference on Interdisciplinary Studies (ICIS 2016) - Interdisciplinarity and Creativity

**Figure 6.** Total values calculated for imports as a percentage of GDP (2000-2009) [1].

**Figure 7.** Values calculated for GNI per inhabitant of Central and Eastern countries (2000–2009) [1].

generated positive effects in their own economic branches.

Undoubtedly, the upward trend of GNI per each economy has been achieved as a result of the reforms carried out by each country as a result of the EU accession process, which has

continuing until 2009.

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**•** The aid granted for the farmers income.

For implementing the established measures, CAP has currently at its disposal up to 40% of the EU budget and CAP budget in 2014 was about 58 billion Euros, according to European Union, 2015. Through their work related to agriculture and forestry, the employed workers in these branches have an important role in providing a sustainable management within rural areas, because in these regions are created and preserved natural habitats including fauna and flora specific for rural areas in various European countries that would otherwise be destroyed. While in the past agriculture represented the basic concern of the European rural areas inhabitants, today this economic sector has decreased as percentage share in GDP of countries with developed economies due to the increase of branches in the manufacturing industry [17].

Younger people believe that agriculture is no longer a profession of great attraction and are choosing professions in urban areas, where the income level is higher. Therefore, through the CAP must be supported the initiative to attract young people in rural areas, in order to ensure the necessary continuity in agriculture, but also the income level should be comparable to those in urban areas. In contrast to the Western developed countries, heavily industrialized, in Central and Eastern European countries, agriculture continues to hold a higher proportion of GDP and higher employment rate of the rural residents in this economic sector. Thus, must be analyzed the space comprised outside large urban areas of the new EU member countries as rural areas in which specific activities are conducted regarding agriculture, forestry, fishing, product manufacturing and where the historical traditions and customs of the rural areas inhabitants are kept from generation to generation. Overall, if we refer to the new EU member countries from Central and Eastern Europe, we can say that their rural area occupies most of their territory and population, as we can see from the graphic representations shown in Figures 8 and 9 [2].

So, if we analyse graphical representations made, there are few Eastern European countries where rural area is less than 85% of the total territory.  For all other countries the rural area occupies over 90% of the country's total territory and for Slovenia the whole territory can be considered as rural area.

**Figure 8.** The share of rural areas as a percentage of total area for the Central and Eastern Europe countries [2].

**Figure 9.** The rural population of the Central and Eastern Europe countries [2].

**Figure 10.** The rural population density in Central and Eastern Europe [2].

in urban areas. In contrast to the Western developed countries, heavily industrialized, in Central and Eastern European countries, agriculture continues to hold a higher proportion of GDP and higher employment rate of the rural residents in this economic sector. Thus, must be analyzed the space comprised outside large urban areas of the new EU member countries as rural areas in which specific activities are conducted regarding agriculture, forestry, fishing, product manufacturing and where the historical traditions and customs of the rural areas inhabitants are kept from generation to generation. Overall, if we refer to the new EU member countries from Central and Eastern Europe, we can say that their rural area occupies most of their territory and population, as we can see from the graphic representations shown in Figures

Proceedings of the International Conference on Interdisciplinary Studies (ICIS 2016) - Interdisciplinarity and Creativity

So, if we analyse graphical representations made, there are few Eastern European countries where rural area is less than 85% of the total territory.  For all other countries the rural area occupies over 90% of the country's total

territory and for Slovenia the whole territory can be considered as rural area.

**Figure 8.** The share of rural areas as a percentage of total area for the Central and Eastern Europe countries [2].

**Figure 9.** The rural population of the Central and Eastern Europe countries [2].

8 and 9 [2].

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Regarding the Eastern Europe rural areas population density, it can be said that large per‐ centage of the total population is established in rural areas and in terms of density values are lower than 20 inhabitants/km2 for Estonia, Latvia and Lithuania, as shown in Figure 10. For the other EU member states average values are recorded, for example, Romania with less than 40 inhabitants/ km2 , Bulgaria with more than 50 inhabitants/ km2 , Croatia with more than 60 inhabitants/ km2 , while for other countries the values are more than 90 inhabitants/ km2 ; the highest value is of the Czech Republic with almost 120 inhabitants/ km2 .

The main economic sectors, specific to the rural areas of Eastern European countries, are represented by agriculture, forestry and manufacturing of raw materials resulting from these activities. Regarding the land areas used in agriculture, in Figure 11 are presented the corre‐ sponding values of land areas used by each country for both agriculture and forestry. Poland and Romania have the first ranking places having each over 14 and 13 million hectares used in agriculture, followed at long distance by Hungary and Bulgaria with more than 4 million hectares each.

**Figure 11.** The land areas used in agriculture by the Central and Eastern Europe countries [2].

**Figure 12.** The land areas used in forestry by the Central and Eastern Europe countries [2].

Referring to land areas used for forestry, as shown in Figure 12, Poland with 9 million hectares and Romania with more than 6 million hectares again occupies the top positions, followed by Bulgaria, with almost 4 million hectares, and Latvia with over 3 million hectares. For the rest of the countries, there are areas between 1 and 2.5 million hectares used for forestry.

**Figure 13.** The employment level in the primary sector [2].

Analysing the employed labour force in the primary sector of Central and Eastern Europe countries rural areas (Figure 13), we can see that Poland holds the first place with over 15 million persons employed, followed by Romania with over 9 million people employed and for the next places there are Czech Republic and Hungary with 5 and 4 millions of employed people. Bulgaria has over 3 million people employed in the primary sector.

Also must be shown the direct contribution of the rural areas primary sector to gross national income (GNI) of the Eastern European countries, as shown in Figure 14, (according to Euro‐ pean Union, 2015). Top positions are occupied by Bulgaria and Romania with the highest percentage share of gross national income (GNI), located around 6%. The following levels are

**Figure 14.** The direct contribution of the primary sector to the gross national income (GNI) of the Central and Eastern European countries [2].

around 5% for Hungary, Croatia and Latvia, and the lowest values recorded just over 2% for the Czech Republic and Slovenia by almost 3% of its gross national income (GNI).


**1. Introduction**

### **1.1. Varistors**

Varistor is an electrical device based on semiconductor materials used for protection against voltage spikes in the electric network, against overvoltage in electronic circuits of low voltage and electrical power systems [1,2].

Due to the high energy absorption, the ceramic varistors become many helpful in protecting electrical circuits, and their electrical properties are highly dependent on their microstructure. The development of devices ever more technological and brings the need for electrical protection due to the sensitivity equipment. The use of varistors as voltage protectors in electronic equipment is very simple: the varistor is directly connected in parallel to the power line of equipment, and in case of an increase in the electrical current on energy network, the varistor rapidly increases the conductivity, allowing the current flow toward the ground. For electrical appliances operating with few voltages, the varistors ceramics are called low-voltage varistors [1–3].

The first varistor ceramics were developed in 1930. They were constituted from compact silicon carbide (SiC) partially sintered and were designed by the System Bell Labs to replace selenium rectifiers that were used in the protection of telephone systems [4]. Over time, the processing of varistors has undergone successive improvements, and in 1968, Matsuoka [3] developed varistors based on zinc oxide with manganese and cobalt as a dopant to improve the electrical properties. One of the disadvantages of using ZnO-based varistors are the large amount of dopant added to ceramic matrix for its electric modification and consequently to its high chemical instability that leads to degradation of the varistor. Castro et al. [5] reported that the trapping of electrons, ion migration and oxygen adsorption are included as ZnO varistor degradation mechanisms. The exposure of ZnO varistors to high temperatures and oxidizing atmospheres leads to excess interstitial ions *DZn* ⋅ and *DZn* ⋅⋅ that migrate through the depletion layer and chemically interact with species that are in the grain boundary, causing decrease and enlargement of the potential barrier, and facilitate the electronic conduction, destroying its varistor property [5,6].

The SnO2-based varistors were introduced by Pianaro et al. [7] as an alternative to the ZnO varistors commercial, presenting nonlinear electrical characteristics similar to ZnO varistors. The SnO2-based system shows more advantages, for example, their simpler microstructure and no formation of secondary phases require a lower concentration of agents modifiers to promote the varistor characteristics and densification and higher chemical and thermal resistances. The use of M2+ ion as dopant improved significantly the densification of the varistor, the addition of M5+ ion promoted electrical conductivity, and the M3+ ion influenced on nonlinearity coefficient.

#### **1.2. Electrical properties**

The electrical properties of varistor ceramics are governed by potential barriers located in the grain boundaries. Potential barriers were formed by the addition of dopants elements to generate defects on crystal network, which segregate to the grain boundary region by diffusion during sintering. The presence of these barriers promotes the large-capacity power absorption and its flow when subjected to electrical overvoltage [4,8].

In denominated "smart ceramics," the ceramic varistor acts as variable resistors, with resistive behavior at low voltages and conductive behavior starting from a specific voltage value, known as the breakdown voltage (*V*R) or breakdown electric field (*E*R) [9,10].

These electrical responses featuring the varistor ceramics as main elements in the manufacture of devices for electrical protection equipment subjected to both low and medium voltages apply directly as of the electro-electronics components (telephony system, computers, medical devices, automotive electronics, industrial automation systems, alarms, transformers, etc.) and for the high voltages used as part of lightning protection devices installed in the terminals of the power substations [11].

The varistor characteristic associated to quality is the nonlinear coefficient (*α*). The higher their value, the greater the varistor efficiency. This coefficient can be obtained through empirical relationships current × voltage (Eq. 1) or current density versus electric field (Eq. 2) and expresses how much the material deviates from ohmic response when required, and it can be explained by a graphic representation (Figure 1) with distinct regions [12–15].

$$I = \mathbb{C}V^a \tag{1}$$

$$J = \mathbb{C}E^{\alpha} \tag{2}$$

where *C* is a constant related to the microstructure.

**1. Introduction**

26 Advanced Ceramic Processing

and electrical power systems [1,2].

atmospheres leads to excess interstitial ions *DZn*

Varistor is an electrical device based on semiconductor materials used for protection against voltage spikes in the electric network, against overvoltage in electronic circuits of low voltage

Due to the high energy absorption, the ceramic varistors become many helpful in protecting electrical circuits, and their electrical properties are highly dependent on their microstructure. The development of devices ever more technological and brings the need for electrical protection due to the sensitivity equipment. The use of varistors as voltage protectors in electronic equipment is very simple: the varistor is directly connected in parallel to the power line of equipment, and in case of an increase in the electrical current on energy network, the varistor rapidly increases the conductivity, allowing the current flow toward the ground. For electrical appliances operating with few voltages, the varistors ceramics are called low-voltage

The first varistor ceramics were developed in 1930. They were constituted from compact silicon carbide (SiC) partially sintered and were designed by the System Bell Labs to replace selenium rectifiers that were used in the protection of telephone systems [4]. Over time, the processing of varistors has undergone successive improvements, and in 1968, Matsuoka [3] developed varistors based on zinc oxide with manganese and cobalt as a dopant to improve the electrical properties. One of the disadvantages of using ZnO-based varistors are the large amount of dopant added to ceramic matrix for its electric modification and consequently to its high chemical instability that leads to degradation of the varistor. Castro et al. [5] reported that the trapping of electrons, ion migration and oxygen adsorption are included as ZnO varistor degradation mechanisms. The exposure of ZnO varistors to high temperatures and oxidizing

> ⋅ and *DZn* ⋅⋅

layer and chemically interact with species that are in the grain boundary, causing decrease and enlargement of the potential barrier, and facilitate the electronic conduction, destroying its

The SnO2-based varistors were introduced by Pianaro et al. [7] as an alternative to the ZnO varistors commercial, presenting nonlinear electrical characteristics similar to ZnO varistors. The SnO2-based system shows more advantages, for example, their simpler microstructure and no formation of secondary phases require a lower concentration of agents modifiers to promote the varistor characteristics and densification and higher chemical and thermal resistances. The use of M2+ ion as dopant improved significantly the densification of the varistor, the addition of M5+ ion promoted electrical conductivity, and the M3+ ion influenced

The electrical properties of varistor ceramics are governed by potential barriers located in the grain boundaries. Potential barriers were formed by the addition of dopants elements to

that migrate through the depletion

**1.1. Varistors**

varistors [1–3].

varistor property [5,6].

on nonlinearity coefficient.

**1.2. Electrical properties**

**Figure 1.** Electric field (*E*) versus current density (*J*) curves of a varistor [16].

The pre rupture region is also named as linear region and has an ohmic behavior when the material is under operation normal tension. The varistor acts as a resistor in this case with a small amount of current (known as leakage current) passing through the material due to the action of the potential barrier formed at grain boundary and preventing the electronic conduction between the grains. The conductivity in this region is of thermionic emission type, i.e., the electrical conduction is strongly dependent of temperature, thus being possible to retrieve information about the resistivity of the material [8,16,17].

The rupture region showed nonlinear behavior, i.e., non-ohmic behavior between the applied voltage and the current that the material is submitted. The conductivity of the material increases with a small variation in the applied voltage, indicating the varistor efficiency that starts to act as a conductor from a specific breakdown electric field (*E*R). Recombination of electron-hole pair at grain boundary interfaces, thermionic emission, and electron tunneling are suggested as electric conduction mechanisms of this region [8,16].

In the post rupture region, the ohmic behavior between the current and the applied voltage is observed once again and is characterized by high current density. The electric conduction in this region is controlled by the impedance of the grains [2,8].

The *V*R value provides the varistor voltage application, and it is a function of a grain size of sintered material. If the composition is fixed, the microstructure becomes strongly dependent on the processing conditions [12,15].

The varistor efficiency determined by the breakdown region can be evaluated by the *α* nonlinear coefficient of the curve in Figure 1, which is used in Eq. 6, derived from Eq. 3, which allows the calculation of the value of *α* by the field data electric (*E*) and current density (*J*) [18,19]:

$$\alpha = (\log\_2 - \log\_1) / (\log E\_2 - \log E\_1) \tag{3}$$

The electric field and the current density are obtained from the measurements of the electric current (I) generated when the sample is submitted to a potential difference (V), according to Eqs. 4 and 5 [18,19]:

$$E = \bigvee\_{\mathbf{d}} \tag{4}$$

$$\mathbf{J} = \bigvee\_{\mathbf{A}} \mathbf{A} \tag{5}$$

*d* is the thickness of the sample and *A* is the electrode area deposited on the film surface. For *α* calculation, the interval of 1 and 10 mA/cm2 of current density was used, i.e., *J*1 = 1 and *J*2 = 10 [18,19]:

$$\alpha = \left(\log E\_2 - \log E\_1\right)^{-1} \tag{6}$$


**4.3 Insulin substitution therapy**

Insulin replacement therapy, also referred to as intensive insulin therapy or basalbolus therapy, is a comprehensive approach to helping patients achieve optimal blood glucose control by mimicking the physiologic delivery of insulin. This approach uses current understanding of factors affecting glucose homeostasis to permit patients to use flexible insulin dosing to match their lifestyles and preferences.

For Type 1 diabetes, a basal-bolus regimen with a long-acting analog and a shortor rapid-acting insulin analog is the most physiologic insulin regimen and the best option for optimal glycemic control [10].


**Acute and Chronic Kidney Diseases**

**1**

*Columbus, Ohio,*

 *USA*

**Congenital Obstructive Nephropathy:**

*and The Research Institute at Nationwide Children's Hospital,*

Susan E. Ingraham and Kirk M. McHugh

 **Clinical Perspectives and Animal Models**

*Department of Pediatrics, Division of Pediatric Nephrology, The Ohio State University*

Congenital obstructive nephropathy is the leading cause of pediatric chronic kidney disease (CKD). Consequently, it engenders a tremendous societal burden in terms of morbidity and mortality and in health care expenses over the lifespan of affected patients. The challenges clinicians face in the diagnosis, prognosis, and treatment of congenital obstructive nephropathy illustrate the utility of developing effective experimental models for the study of this complex disease process. In this review, we characterize congenital obstructive nephropathy with its myriad causes and manifestations, outline current standards of diagnosis and care, and discuss experimental animal models with relevance in unraveling

Congenital obstructive nephropathy is a complex process of pathologic changes in kidney development and function that arise when antegrade urine flow is impaired beginning *in utero*. The term *congenital obstructive uropathy* is frequently used to describe this condition. However, every urologic obstruction – whether anatomic, mechanical, or functional – should be approached with the knowledge that obstruction can affect the kidneys. For this

Intrinsic anatomic obstructions may occur in isolation or accompanied by other pathology such as renal hypodysplasia. Functional obstructions also occur, which may be transient and self-resolving, or chronic with potentially profound consequences on renal function. Although the etiologies of congenital obstructive nephropathy are myriad, any restriction of urine flow has the potential to produce hydronephrosis, altered renal development, and progression of CKD. This direct link between obstructed urine flow and abnormal kidneys represents a central paradigm of urogenital pathogenesis that has far-reaching implications

Congenital obstructive nephropathy is the most common cause of CKD in children and is among the top three etiologies of pediatric end-stage renal disease (ESRD; NAPRTCS, 2009).

clinical conundrums and molecular mechanisms of this important renal disease.

reason, we prefer the term *congenital obstructive nephropathy.*

**2. Epidemiology of congenital obstructive nephropathy**

(Woolf & Thiruchelvam, 2001).

**1. Introduction**