Non-compliance with prescribed treatment is an important cause of preventable mortality and economic burden. Recognition of the factors for non-compliance with the therapeutic orders of specialists from the perspective of patients and health care providers sheds more light on the issue for policymakers and stakeholders. The current study aimed at determining the factors for non-compliance with therapeutic orders in outpatient clinics in Kerman, Iran.The current qualitative study was conducted using the phenomenological method and semi-structured interviews with 10 patients, five specialists, and four health care managers and treatment officials in outpatient clinics in Kerman. The interviewees were selected by purposive sampling. The codes extracted from the interviews were transcribed using conventional content analysis to identify the viewpoints. The MAXQDA 10 software was used to analyze the data.The reasons for non-compliance with specialists’ orders were categorized into five themes including patient-related (patient-centered), disease-related, therapy-related, the healthcare provider related , and socioeconomic factors. Themes were composed of fifteen categories and forty-one sub-categories. The dominant sub-categories extracted from interviews were health literacy and knowledge of the patient, communication and patients’ trust in physicians and direct costs of treatment.This study identified a wide range of different individual, disease, treatment, health care provider, and socio-economic factors and the interactions between them which may result into non-compliance with therapeutic orders prescribed by specialists. Therefore, specific attention should be paid to integrate the service provision system into the collaborative approach of the patient and his/her family in order to promote the level of compliance with therapy and care in planning and policy-making to improve the health service provision system.The online version of this article (10.1186/s12913-019-4229-4) contains supplementary material, which is available to authorized users. The goal of any prescribed medical therapy is to achieve the desired outcomes in patients. Despite the best efforts of specialists, patients’ non-compliance is still a major problem that prevents the clinicians to achieve the desired therapeutic outcomes. Hence, since 1970s, therapeutic compliance is considered a major concern in clinical settings due to its widespread nature [The World Health Organization defines the concept of compliance as the accomplishment of some behaviors such as taking prescribed medication, healthy lifestyle, and following the recommendations provided by health caretakers ; otherwiNon-compliance with treatment refers to the non-use or discontinuity of the treatment process and inattention or failure to follow the prescribed treatment by the patient. Not taking medication, failure to modify lifestyle or diets, frequent changes in the treatment process, and failure to follow or defectively perform the diagnostic tests, imaging, radiography, etc., are some examples of non-compliance with therapy , 3.According to results of relevant research in Iran, 30% of patients with tuberculosis were non-compliance with treatment regimen . the patFrom the perspective of healthcare providers, non-compliance with therapy is an important clinical issue due to two factors: first, it has significant impacts on clinical and therapeutic outcomes and leads to disease progression, increased visits to outpatient clinics, re-admission, and hospitalization. When patients do not follow the therapeutic plan, the effects of the plan are not realized, which may leads to treatment failure and life-threatening reactions . Non-comMany factors are involved in patients’ non-compliance with therapy. It is vital for the treatment team to be aware of the status of such factors in order to reduce the severity of disease complications in an effective manner . The necThe current qualitative study employed the phenomenological method. Phenomenology is a systematic and subjective method used to describe the individuals’ experiences and understand their meanings . The resThe study population consisted of outpatients, specialists, and managers of clinics. In this study, the purposive sampling method has been used. In this way, patients who were referred to outpatient clinics and also specialists and clinical managers with at least five years of experience in outpatient settings from diverse specialties with research background were selected. First author (i.e. SN) referred to outpatient clinics in Kerman city and those who voluntarily tend to participate in this study were selected. Study aims were described and the written informed consent was obtained before the interview begins. The study sample consisted of 10 patients, five specialists, and four healthcare managers and treatment officials; thus, 19 interviews were conducted. All interviews were conducted by SN and VYF.Before the interviews were conducted, a quick review of literatures was conducted as an electronic search through valid databases in order to recognize concepts and provide an interview guideline. The interview guideline was set up based on the review of the most important studies; besides, an additional question, which was necessary to identify each additional factor, was added. The questions included in the interview guide is presented in the appendix, Additional file Afterward, semi-structured interviews were conducted with the participants on the specifically reviewed subject. After explaining the concept of non-compliance with therapy and the goal of the study to the participants, the researcher conducted the interviews by asking the prepared questions and attempted to pull out their experiences with no specific bias.Interviews were conducted at the appointed time and place agreed upon by the participants. In order to conduct interviews with doctors and managers, an appointment was made, and the interviews were conducted when they had no patients or at their resting time. Interviews with patients were conducted in the service provision setting. All interviews were audio-recorded and transcribed verbatim. The average time of interviews with specialists and patients was 35 and 20 min, respectively. The minimum and maximum time of the interviews was 10 and 60 min, respectively. The interviews continued until no new reasons for non-compliance with therapy emerged and data were saturated.Each interview was immediately transcribed verbatim, transferred into the software, and used as a guideline to conduct the next interviews. In order to accomplish this step, the transcribed interviews were transferred into the MAXQDA 10 software and data were coded. Conventional content analysis was employed to code the interviews. Content analysis is a research method used to objectively and regularly describe the obvious content of communication messages . The conIn order to accomplish content analysis, the interviews were independently coded by SN and MHM and any uncertainties and disagreements were discussed with participation of the first author (i.e. VYF) until consensus reached. The transcriptions were reviewed several times to obtain a complete understanding; then, the analysis was performed based on the perception of transcriptions. Some codes were assigned to keywords and phrases that reflected participants’ opinions. In the next step, the codes were compared and in the case of discrepancy, some discussions were made to reach consensus. The codes were reviewed several times in meetings, and were classified based on the similarities and differences of contents. According to the quality of the relationship between the contents of texts, the codes were combined and organized, and the main topics that described the codes were extracted. In the next step, the codes and concepts were defined. In the end, a summary of the definitions and categorized concepts were provided to be reviewed by the researcher. Then, the classification was completed and finalized. We also run and checked all the stages included in a qualitative study according to the important items proposed in the checklist named as criteria for reporting qualitative research .The four criteria proposed by Guba and Lincoln for trustworthiness including credibility, transferability, dependability, and confirmability were used to ensure the validity, accuracy, and stability of the qualitative data . For thewe employed triangulation in sampling. We used main different stakeholders for sampling, including healthcare and treatment officials, specialists, and patients who are directly related to the phenomenon of non-compliance in therapeutic orders.The current study was approved by the ethics committee of Kerman University of Medical Sciences with ID number IR.KMU.REC.1397.040. No personal information is reported here, and all names are pseudonyms . Notes were taken during interviews and if participants agreed, they were audio-taped.Among the healthcare specialists and managers, 45% were male and 55% female; 67% were faculty members and 33% non-faculty members; 56% were specialists and 44% healthcare services managers or treatment officials. Among the participating patients, 40% were male and 60% female and their education level ranged illiterate to Master of Science Table . A summaThe factors identified from the analysis of interviews with specialists and patients were classified into five themes, fifteen categories, and forty-one subcategories. The themes extracted were including individual-related (patient-centered), disease-related, therapy-related, the healthcare providers-related , and socioeconomic factors Table . FurtherIndividual factors of patients were classified into four categories including demographic, cognitive (belief), psychological (negative attitudes toward treatment), and behavioral factors.The factors identified in this class consisted of six subcategories, including age, gender, education level, marital status, job type, and ethnicity.“When an individual becomes older, his/her level of hearing is lower, and there is the possibility that doctor’s statements are not heard correctly, and the instructions are not received accurately” (M1).“For some patients, especially with aging, no one may exist in order to prepare their medications for them; necessary therapeutic actions may be interrupted for two or three months or treatment process may be done with delay” (S4).“As people grow older, they become more timid and conservative, and they pay much more attention to the recommendations and instructions than young people” (P8).With aging, individuals may have vision, hearing, and memory problems affecting how to take their medications , and they may not be able to meet compliance with therapy. In addition, with aging, due to reduced physical and mental abilities, they need the others to remind and prepare their medications for them. The interviewees mentioned age as a parameter that can be related to non-compliance with therapy.“Males usually show less compliance with therapy than females; therefore, gender can be an effective factor in non-compliance” (S1).“I think females have better compliance compared with males, since they are sensitive even to very minor problems, and they quickly refer to doctors and try to do as the doctors say. However, males are more carefree, and they say that there is not a very important problem, except in the cases that their diseases become very serious; then they pay attention to the doctors’ instructions” (P8).Of the interviewed individuals mentioning gender, most of them stated that males are more prone to non-compliance than females.“Education can also be effective. I think that individuals with lower levels of education have better compliance; for example, some uneducated people around me believe that they should follow doctor’s instructions, or they should accurately take their medications based on the doctor’s instructions. However, an educated person may think that some of these instructions are not necessary, or the medication dose is excessive, and they may not have complete compliance” (P8).“Individuals with higher levels of education have better compliance as a result of their higher level of knowledge and due to the issue that they are more aware of the importance of doctor’s instructions” (P5).In terms of education, interviewees had different opinions. Some of them believed that people with higher levels of education have better compliance, and some of them agreed with its opposite. The patients said:“……how do the doctors themselves take their treatment, either they themselves diagnose their disease or they behave like ordinary people; either they refer to different doctors or since they themselves are doctors, they believe that their own diagnosis is more accurate; whether they follow non-compliance with specialists and how is the compliance status of general practitioners with specialists? Either the specialty and work area of an individual is related to health sector or he/she is working in other areas. What is his/her specialty? ....” (M1).People are involved in different work areas in the community. When people become ill, their work area may affect their compliance, as one of the interviewees stated:“….a driver may not use his/her prescribed soporific medications due to his/her job” (P7).The interviewees also mentioned the individual’s job type and its characteristics such as job-related travels and job conditions, as factors that can lead to non-compliance:The individual factors related to cognition consisted of eight subcategories, including health literacy, patient knowledge, health importance degree for the individual and health motivations, individual’s recognition and perception from nature, previous experience, religious beliefs’ perception and believing, reasoning power and decision-making attitudes and forgetfulness.“….what is the recipient’s health literacy level? Are the doctor’s instructions understandable for the patient? For example, if the doctor says to the patient that take this medication three times a day, is its meaning understandable for the patient in terms of his/her cognition? Some phrases may also be literally understood differently; for example, if the doctor says to the patient to come tomorrow, he/she might think that he/she should come two days later since in his/her culture, in order to say come tomorrow, you should say come “morning”(M1).“People’s low literacy makes them as individuals who are not aware of the importance of following doctors’ instructions” (M2).An individual’s inability to receive, interpret, and perceive the primary information, health instructions, and services that are necessary to make a proper decision can affect non-compliance. A manager and a specialist in community medicine said:“Some patients have chronic diseases. They cannot accept their diseases or it is hard for them to accept their diseases. For example, to some extent, they control their blood sugar or pressure and after that they think they become better and it is not necessary to follow doctors’ instructions anymore. Consequently, they refer again to doctors with high blood sugar or pressure” (S4).“The patient does not have enough information about the disease and medications. For example, the patient may not take his/her antibiotics completely, and he/she is not aware of the consequences of taking such medications incompletely. Therefore, due to his/her insufficient knowledge, he/she takes his/her antibiotics only for some days, and after becoming better, no longer takes his/her medications” (S2).“The individuals may not be aware of the consequences that their non-compliance can cause for them” (P2).The lack of patients’ information and knowledge about diseases and treatment, lack of their awareness of complications and benefits of therapeutic orders and the consequences of non-compliance were among the factors mentioned in the interviews.“The mindset that the patient has from his/her previous referrals to doctors may create this feeling in him/her that income is more important for them than their patients” (P6).The importance degree that individuals give to themselves is different. In addition, the individuals’ motivation for treatment may be different, and it seems that this issue can affect patients’ non-compliance. Another factor that can affect individuals’ non-compliance is their experiences. If an individual has an unpleasant experience from his/her previous referral to a doctor or treatment process, this can lead to non-compliance in the patient. In this regard, it was stated:“How are an individual’s recognition and perception from nature, life’s philosophy, and its purpose? And how is an individual’s perspective about his/her being against the world? If the patient considers his/her healthfulness as a deposit, his/her therapeutic compliance will increase. If the patient considers his/her healthfulness as a right, he/she may have a lower level of compliance. Therefore, an individual’s recognition about how his/her worldview can affect his/her therapeutic compliance” (M1).“How is the community’s culture, in which the individual lives, towards the specific therapeutic method? For example, a particular treatment may not be accepted by the residents of a specific village or city according to their customs” (P5).“How are the individuals’ religious beliefs and their perspectives about healing and miracle? Do they follow their treatment process along with their beliefs in healing and miracle or they abandon their treatment process because of those beliefs?” (M1).“Many non-professional individuals such as neighbors and family members interfere with medical issues. These people state their experiences for the patient, and there is even a proverb in this regard, which says “Do not visit a doctor, visit a person who had the same disease.” For example, if someone has a kidney stone, the other individuals around the person that had the experience of kidney stone may give him/her guidelines. Most of the time, in such cases, individuals don’t know that the clinical conditions of patients may be different. A therapeutic method for a kidney stone with a diameter greater than 1 cm in the different places of the kidney may not be similar to the therapeutic method of very small kidney gravel” (S3).“People’s attention to the others’ recommendations…. anyone may suggest a doctor whose performance is better than the others, and unfortunately, some people pay much attention to others’ suggestions” (P6).“Some people refer to various doctors, and since they do not become better after a long period of time, they become disappointed and lose their motivations for any further treatments. For example, one of our acquaintances referred to doctors for infertility treatment for eight years, due to not getting desirable outcomes from her treatment during this long period of time, became disappointed and abandoned her treatment process” (P7).To believe in specialisms, cultural features and values, ethnic-religious beliefs, folk perspectives, and non-professional interventions, individual’s perception, expectations and judgment from treatment period, medications effectiveness perception, and mental stereotypes may lead to patient’s non-compliance with therapeutic orders.“Sometimes, we may forget the doctor’s instruction, especially about taking medications or when the doctor says to us please refer again at that time. We may remember these issues after a while” (P1).“Sometimes, people say different things to you and you get confused. For example, when you have a disc herniation, the doctor may say to you that you need surgery to become better, but some people who are around you may say to you that surgery cannot be effective and you may get worse. In such cases, you get completely confused.” (P9).Some individuals consult with other people when they want to decide on doing doctor’s instructions, and therefore, due to this consultation, the patients may become hesitant in decision-making and following doctor’s instructions. In some cases, the patient may forget the prescribed instructions. The patients said:The psychological factors that patients mentioned as factors for therapeutic non-compliance were classified into five subcategories, including fear of disclosing information (stigmatization), obsession, depression and weakness, anxiety, and fear and denial.“An addict that consumes drugs is often afraid of going to the laboratory, since he/she fears that someone may discover his/her addiction….” (P6).“Sometimes, people do not refer to doctors since they are afraid that the outcomes of their therapeutic actions  may indicate a dangerous disease. They say that I am ok now, and if I refer to a doctor, I will become ill” (P6).The participants stated that the patient might not follow his/her treatment process as a result of stigmatization and fear. In addition, it was stated that obsession in the form of irrational and annoying thoughts or conceptions compel an individual to do an action repeatedly, forcibly, and involuntarily, for example, frequently changing his/her doctors. Depression and weakness, anxiety, and fear are among the other factors that interviewees mentioned as non-compliance factors:Habits and the individual’s ability to change them  were classified in this category.“Sometimes, an individual is in a party in which all people are eating very delicious food. In such a situation, although the individual knows that he/she should not eat that food, he/she cannot control himself/herself and consequently eats it” (P9).Participants stated that individuals have different lifestyles. They do not accept some of their behavioral habits such as diet restrictions and smoking avoidance, and they cannot change them easily.Disease characteristics were classified into three categories, including disease type, disease stage and severity, and comorbidities (disease complexity and having chronic diseases)/ Underlying diseases.“Non-compliance is different based on the disease severity; either the disease is at early stages and does not have a lot of symptoms or the disease severity is very high and it has a lot of symptoms” (S5).“Maybe, the patient has several diseases simultaneously, and it is necessary for him/her to take a large number of medications for each of his/her disease, which is not possible for him/her” (S4).The type of individual’s disease and its symptoms, the disease appearance and manner, the disease stage and severity, and having several diseases simultaneously can affect non-compliance. The specialists said:Therapy-related factors consisted of four categories including the route of administration, treatment complexity, duration of the treatment period, and medication side effects.“Sometimes, we get tired of continuously taking medications, and we do not have any motivations to continue treatment.” (P2).“The side effects of some medications; for example, I referred to a dermatologist, and he prescribed tetracycline for me, and since I have also bowel disease, I could not take this medication” (P6).The prescribed treatment method may not be compatible with the person, or treatment complexity and the other chronic diseases of an individual in addition to his/her disease can lead to non-compliance. The long-term treatment period of some diseases and the side effects of medications can also lead to non-compliance.The healthcare-provider-related factors were classified into two categories, including the Individual attributes and service provision system characteristics.“The features and attributes of a doctor in his/her medical performance, the level of his/her accuracy, and his/her literature in relation with patients are important factors. The same medication may have different effects if it is prescribed by doctors with different personal features” (S3).“It happened several times to me that I referred to doctors, and they could not diagnose my disease or misdiagnosed. Therefore, I think that some doctors have insufficient knowledge, and cannot diagnose accurately” (P1).“How is the doctor’s verbal communication, and how does the doctor listen to patient’s talk? For example, my mother refers to a doctor who lets her speak about her disease. Then, my mother says that the doctor was very good, and consequently, she follows his/her instructions more accurately and much better” (P3).“Some doctors do not pay any attention to patients’ opinions. They do as they wish, since they think that only they can understand, while they may prescribe something for the patient that it is hard to follow. But, if they ask patient’s ideas in this regard, it would be much better” (P10).“Sometimes, you call a doctor’s office, and his secretary says “the doctor comes at 11 a.m.” But when you go to the office, the doctor comes at 2 p.m.; or sometimes after waiting for an hour, the secretary may say “please go, the doctor comes at 5 pm” (P2).The Individual attributes mentioned in the interviews were classified in eight subcategories, including ethics and behavior , background and experience, therapist’s literacy, fame, communication, communication and patients’ trust in physicians, the extent of doctor’s recognition of patients and doctor’s decision-making attitude (prescribing a lot or a few number of medications), power enforcing attitude (therapist to patient), and professional principles.“... If they refer to a government system, other people label them, and thus they refer to a private system” (M2).“Since the specialties are very various, and many of the diseases may relate to several specialists, the patients in such cases cannot decide which specialists they should refer to, and they may refer to several doctors for several times to find the main cause of their disease” (P6).Regarding the service provision system, the interviewees stated six subcategories that could affect the non-compliance. These subcategories were ownership and nature, service provision system structure, payment system, access, legal guarantees, and the interaction of traditional and modern medicine. A specialist in community medicine and a patient said:“Incorrect and low tariffs in clinics increase the unnecessary visits and non-compliance” (S5).“When we refer to receive health services, it is very important for us to know that how many of the services are covered by the insurance …” (P5).The determination of payment method for different services may lead to doctors’ unnecessary prescription for their patients. The level of payment is the price specified for the services, and it is very important. There are different types of insurance, and the number of services covered by each of them is different. Therefore, the type of patient’s insurance can be effective for non-compliance.“The services access facility; whether the services are available to the individuals or they should spend a lot of time in order to receive the desired services either in terms of waiting time and bustle or passed distance” (P7).“Some medications, especially the ones necessary to treat specific patients cannot be found easily, or they may only be found in some metropolises” (P2).“How is our information system? How are the information infrastructures in our health system? Do we have electronic health records? For example, when we refer to a doctor, and he/she wants to see our radiology result for diagnosis, it would be very useful if he/she can see our previous radiographs during the past 10 years in his/her computer. However, if he/she cannot have access to our previous radiology and ask us to repeat it, then we may say that I cannot do it since I have done it recently, and then, the level of non-compliance will increase. Therefore, information infrastructures can be very effective, especially if there is an information system, which can identify that a patient has referred to several doctors for his/her disease. Moreover, especially, when insurance systems can control the patient’s referrals to doctors, and there is a disease care system to control the patient and if he/she shows inappropriate behavior, then this system can follow up this patient and help him/her to solve his/her problem” (M1).Access was one of the factors that the interviewees stated. The concept of access is related to the opportunity and ability to use services; actually, it means the existence of a set of circumstances in which an individual that needs health services can properly use them. The queue is sometimes so long that the person cannot receive the services, leading to his/her leave. In addition, the lack of physical facilities, geographical access, medication access (medication rareness), information infrastructures, equipment, and technology, each can be a reason for non-compliance.“There are some people who are not doctors; but due to lack of supervision or the existing beliefs, some patients refer to them, and they provide some services for those patients. Even, some of these fake doctors, unfortunately, ask the patients to follow the instructions they give, and that the patients should stop all other therapeutic orders and protocols” (S3).“When a patient observes the unethical communications of doctors with specific drugstores, laboratories, etc., he/she may not pay much attention to those doctors’ instructions anymore” (P4).Lack of supervision, (the claim of) doctor’s misconduct, and corruption in service provision are among the other system-related factors that can affect patients’ non-compliance.“Individuals’ beliefs toward traditional or chemical medications are different. For example, I refer to a doctor and he/she prescribes medications for me; since I think chemical medications are harmful, I use traditional ones. However, some of our family members believe that chemical medications are more effective for their treatment” (P8).The systematic interactions between traditional and modern medicine affect non-compliance; whether these two systems have conflicts with each other or one of them is more efficient from the individuals’ perspective.This theme comprised two categories including economic and social issues.The economic issues of non-compliance with doctor’s instructions consisted of two subcategories including direct and indirect costs of treatment.“Expensive medications and treatments can play an important role. Some people cannot pay the costs of some medications and treatments; therefore, they give up purchasing their medications and following their treatments” (M3).“Sometimes, doctors recommend eating a special kind of fruit or other items for the patient, and in some cases the patient’s financial condition is not very good, and he/she even hardly purchases his/her essential necessities. Consequently, he/she cannot bear the additional costs of doctor’s instructions.” (S1).“Sometimes, the patient’s medication may become over, and at the same time, he/she may not have enough money to buy his/her medication again. Therefore, taking medication stops for that patient” (P10).Low income and inability to pay health costs are among the most important factors mentioned in the interviews. During the disease period, in addition to the main costs of treatment, other indirect costs of treatment such as transportation, residence, diet are imposed on the individual; due to these extra costs that the individual may not be able to pay, he/she, unfortunately, is forced not to follow the doctor’s instructions anymore.Social issues consisted of seven subcategories including job security (anxiety about job loss), concerns and environmental stress , advertising, media and cyber space, pride in treatment, and support system.“Although the fact of disease’s importance and the issue that the disease is with you until the end of your life were explained to the patients, due to their high level of concerns and engagement, they did not pay attention to completion and follow-up of their treatment” (S4).“The people’s concerns are so great that the issue of medication compliance is unimportant to them…” (M2).Sometimes, compliance with doctors’ instructions may have inappropriate occupational outcomes for the individual; therefore, the individual prefers non-compliance with them. Some interviewees also mentioned that some people have such complicated social concerns and problems that the issue of health and compliance with doctors’ instructions become unimportant for them.“Patients compare the doctors’ instructions with the materials they have read on the Internet, and in this way, they obtain information about the subject” (P3).Due to extensive communications and easy access to information, many people, when referring to doctors to receive prescribed instructions, search the prescriptions on the Internet or adapt them to the information that they receive from media and cyber space; if they find some contradictions between them, they may decide not to follow those instructions.“The social support system of the person who needs treatment is important. For example, if the patient is too young, how is his/her parents’ support system for his/her compliance with the disease? And, if the patient is old, how do the individuals who support him/her, for example, his/her children affect the patient’s decision making, and conduct psychological support?” (M1).Insufficient support from family, friends, and social groups is another reason for non-compliance.Social issues consisted of seven subcategories including job security (anxiety about job loss), concerns and environmental stress , advertising, media and cyber space, pride in treatment, and support system.“Although the fact of disease’s importance and the issue that the disease is with you until the end of your life were explained to the patients, due to their high level of concerns and engagement, they did not pay attention to completion and follow-up of their treatment” (S4).“The people’s concerns are so great that the issue of medication compliance is unimportant to them…” (M2).Sometimes, compliance with doctors’ instructions may have inappropriate occupational outcomes for the individual; therefore, the individual prefers non-compliance with them. Some interviewees also mentioned that some people have such complicated social concerns and problems that the issue of health and compliance with doctors’ instructions become unimportant for them.“Patients compare the doctors’ instructions with the materials they have read on the Internet, and in this way, they obtain information about the subject” (P3).Due to extensive communications and easy access to information, many people, when referring to doctors to receive prescribed instructions, search the prescriptions on the Internet or adapt them to the information that they receive from media and cyber space; if they find some contradictions between them, they may decide not to follow those instructions.“The social support system of the person who needs treatment is important. For example, if the patient is too young, how is his/her parents’ support system for his/her compliance with the disease? And, if the patient is old, how do the individuals who support him/her, for example, his/her children affect the patient’s decision making, and conduct psychological support?” (M1).Insufficient support from family, friends, and social groups is another reason for non-compliance.Based on the current study results, five themes were extracted indicating the factors for non-compliance with therapeutic orders. The study results showed that various factors related to individual, disease, therapy, service provider, and social and economic issues affect non-compliance with receiving services in outpatient clinics. Some of these subcategories such as health literacy, patient knowledge, communication and patients’ trust in physicians and direct costs of treatment are among the most important ones mentioned in most interviews.The overall framework to categorize the themes was consistent with that of a systematic review of studies that examined the factors influencing treatment acceptance from the perspective of patients . GholamaOne of the themes that the interviewees mentioned as an effective factor of non-compliance with therapy was individual-related factors. Butterworth et al., stated that patients that can read and understand medication labels have better compliance . ShepparEmotional and psychological aspects were among the other issues that interviewees mentioned as individual factors; in this regard, previous studies also showed that shame, discrimination , depressThe disease and therapy-related factors were the other themes that interviewees discussed. Numerous studies also indicated that treatment compliance can be affected by disease type , 37, discommunication and patients’ trust in physicians were among the main factors related to service providers pointed out by many interviewees for their non-compliance. Not listening to the patients’ talks, not providing adequate explanation by doctors about the disease and justification of patients about the disease, the necessity of following instructions and convincing patients to comply with therapeutic orders and lack of patients’ participation in planning their treatment plan are among the factors that increase non-compliance. Bermejo et al., in their study indicated trust plays key roles in treatment, participation, and encouragement . In addiOther important factors for non-compliance are social and economic issues. In this regard, the results of the study showed that some of the doctors prescribe medications for patients without paying much attention to their economic conditions. Some people have low incomes and they are not able to buy some services; thus, the high cost of some treatments can be among the factors for non-compliance. Therapeutic costs can be a large part of patients’ living costs, and in lower socioeconomic categories, such costs increase non-compliance , 45. StuGoodhand et al., in their study on patients with inflammatory bowel found that non-compliance was more frequent in patients with lower socioeconomic status . The resThis is one of the first studies to our knowledge that a qualitative investigation has been undertaken of compliance with therapeutic orders prescribed by specialists within the setting of outpatient clinics in Iran. Our study also had some limitations. One limitation of this study is related to the generalization of the results considering qualitative nature of the study. This study was not designed to be generalizable, but rather to explore providers and patients’ perspectives on the factors affecting the compliance and noncompliance of the therapeutic orders. Furthermore, although many participants were very exposed to declare their perspectives during interviews, they may still have withheld some of their thoughts about noncompliance of the therapeutic orders prescribed by specialists. Furthermore, the selected patients and providers in this study may not be representative of all patients and providers. Since the current study was related to outpatient clinics in Kerman, and due to the different conditions of the individuals and the system in terms of transferability, the results should be cautiously interpreted for other settings and contexts. Another limitation is that although there is a relatively strong research background related to non-compliance with therapeutic orders, most these studies are disease based and often conducted on hospitalized patients in Iran. Thus, there was no evidence enough using similar methodology about outpatient clinics in Iran which limited the comparisons with local evidence. So it is necessary to be conducted further research to identify the factors affecting the compliance and adherence with prescribed therapeutic orders. Precipitancy, stressful environment and patients’ impatience in outpatient clinics’ interview environment were among the other limitations; however, it was tried to use a quiet environment to interview the patients. Lack of cooperation of some specialists due to their busy was another limitation, which was tried to overcome by conducting the interviews with several referrals and getting an appointment with them.The current study results showed that non-compliance with therapeutic orders in outpatient settings depended on various factors that interacted with each other including individual-related factors, disease characteristics, therapy-related factors, health service provider features, and socioeconomic issues.Therefore, health professionals and policymakers should be aware of such factors and consider them when designing programs to improve compliance with treatment. Education, adequate notification about diseases and their treatments can be useful to promote the individuals’ health literacy and knowledge. When doctors visit patients with low health literacy, they should speak slowly, repeat the information, use simple and non-medical language, and utilize learning techniques. Establishment of good communication and gaining patient’s trust, increasing patient participation in therapeutic decision-making, engaging the patient in designing his/her treatment plan, explaining accurately about his/her disease and treatment, and answering his/her questions can reduce non-compliance. In addition, considering the patient’s economic condition and therapeutic costs is one of the important factors that policymakers should pay attention to when they decide to improve the service provision system.Additional file 1:The interview protocol for the semi-structured interviews. (DOCX 13 kb)


The present research aims to investigate the psychosocial phenomena of obedience and disobedience in young adults residing in the United States, as a replication of a previous study by Pozzi, Fattori, Bocchiaro, and Alfieri (2014). We utilize social representation theory as a means to better understand and define (dis)obedience, a behavioral dimension of the concept of authority. The analysis was conducted using a concurrent mixed methods design. One hundred and fifty-one participants completed a self-report online questionnaire. The results indicate that participants see both obedience and disobedience as related to an authority. Obedience was mostly perceived as an ability to be responsive to laws, social norms, or physical authorities, as well as a positive social object. Disobedience, instead, was defined as a failure of a negative line of conduct. These results differ from previous research, contributing meaningfully and pragmatically to the theoretical debate on (dis)obedience. Theoretical and practical implications of these findings are discussed. Authority relationship, obedience, and disobedience are fundamental components of everyday life within family dynamics , the worTraditional literature on (dis)obedience has assumed and verified that Milgram’s assumption and definition of (dis)obedience is valid worldwide . The choparticular group  shines particularly useful light on issues of (dis)obedience . Social ar group .per se. Obedience and disobedience, in the Italian context are related to the concept of authority . While mostly considered an uncritical response to laws, social norms, or physical authorities, disobedience was also defined as an active, conscious line of conduct in which some issues related to freedom and society. This advancement highlights the positive and prosocial element of disobedience.Within the context of Italian culture, The pertinence of SRT  in studycontent, a set of beliefs, attitudes, and scripts, and is organized in a precise structure. nucleus, and a periphery. Nuclear elements give unity and stability to the representations, while peripheral elements allow plasticity to the representation, giving persons belonging to the same social group, the possibility to have different conceptions of the same representation. All the information, beliefs, ideas, and attitudes related to a specific object of representation, give meaning to the representation according to their place in the structure. Specifically, nuclear elements are key components defining the social object, while peripheral elements can be behavioral tendencies, the expression of a minority group, or elements fading in or out from the representation  A first periphery (high frequency and low rank), representing less central and more open to change but still representative aspects of the SR. (c) the elements of contrast (low frequency and high rank), which are characteristic of a possible minority within the considered social group; these elements are more open to change than the elements of the first periphery. (d) Finally, a second periphery (low frequency and low rank), representing the least representative characteristics of the minority  and presents the highest degree of openness and flexibility to change  open-ended self-report questionnaires will be used to collect verbal material about a specific social object - (dis)obedience; (2) the contents depicted in this verbal material should be analyzed with regard of both their frequency of appearance (indicative of how much they are shared within a group) and the rank of relevance (indicative of how much they are important within a group) . The reso change . Some scThe need to communicate about obedience and disobedience reaffirm the salience of these two social objects, making them important representational objects. Through interpersonal communication, people share knowledge about authority relationship and obedience and disobedience, shaping beliefs and attitudes useful to take a position and to act properly in the social world. In sum, SR can be seen as tool for communication and to behave in social interactions. It is the transformation of abstract concepts in real guidelines that people can follow to be functional in the social world.Given these premises, this paper aims to replicate the study by i aged between 19 and 25 years  took part in this study on a voluntary basis and signed participation consent forms. Seventy participants  answered the questionnaire related to obedience  while 81 participants  answered the questionnaire related to disobedience . One hundred and eleven participants (73.5%) identified as university students, 27 (17.9%) identified as student-workers, and 8 (5.3%) indicated they were workers. Eighty-nine (58.9%) participants stated that they have a college degree, 58 (38.4%) indicated having a high school degree, and three (2%) reported having a PhD. Participants were recruited through a convenience sampling procedure in two North American higher education institutions located on both East and West coast. The study was approved by the institutional review boards of the institutions where data collection took place.A sample of 151 U.S. young adults A mixed-method research design was conducted. The central premise of using mixed methods is that an intentional and synergic integration of quantitative and qualitative approaches provides a better understanding of research problems than either approach alone, as it provides more comprehensive evidence for studying a research problem, especially when it is very complex and asks for multiple sources of data . By usincontent of the representation, on each single data corpus (one for obedience and one for disobedience), we first labeled the collected open answers (Level 1-coding), then we identified groups of labels which have similar meaning and clustered them identifying main overarching themes (Level 2-coding), and finally explored and analyzed the relationships among the themes into a concise, coherent narrative which “connects” the emerged themes. At first, the four judges independently completed the analysis on both obedience and disobedience, and then, as a group, they finalized the analysis through a negotiation process.In order to analyze the structure of the representation, has been recreated by inserting the terms, results of the free associations, in Evoc2000 ;Obedience” for half of the sample, “Disobedience” for the other half) and to rank them by importance. To disambiguate nouns and adjectives, subjects were asked to briefly explain their choice . A common idea presented by the participants was the idea that obedience is the tendency of “doing what one is told.” For example, “Obedience is when you obey certain task, to comply with rules and laws” (Participant 1); “Obedience is when you listen to what is being told” (Participant 2). Participants used different labels to indicate how the authority asks for obedience: iii, norms, rules, lawsorders and guidelines (Level 1-coding). Participants defined obedience as “how well you listen to directions, laws or guidelines and how well you follow them” (Participant 69). They also defined it as “willingly following laws, rules, guidelines, and expectations” (Participant 67), as well as “following the rules set by someone else” (Participant 45). Authority was mainly considered in a one-to-one relationship (Level 2-coding) . However, a few participants indicate society, as a whole, as an authority, defining obedience as “being able to follow rules or direct commands given by some[one] of higher authority then you” (Participant 10) and as the tendency to follow “the norms of our society” (Participant 19).According to the participants in the study, the term obedience evoked an ability (Level 2-coding), which is something that individuals learn since childhood. Some participants indicated how obedience is “the ability or willingness to follow something” (Participant 50), while others defined it as “one’s ability to remain faithful and committed to something” (Participant 46). Participants conceive different ways of being obedient (Level 2-coding), from agreeing and willingly accepting the order to blindly obey. In this context, participants described it as “following directions and accepting to agree about something” (Participant 19), “being able to listen, obey, and confirm with what you are told, but respectively and with no hesitation” (Participant 25), and “doing things that may go against your personal preference in order to support a greater overall good” (Participant 71). Loyalty (Level 2-coding), was defined by participants as faithfulness towards people who depend on your action. For example, a participant reported how “being obedient is remaining faithful to those who you care about and to those who depend on you for fulfilling certain wants or needs” (Participant 37). Similarly, another participant defined obedience as “one’s ability to remain faithful and committed to something” (Participant 46). From participants’ answers arises a positive view (Level 2-coding) of obedience. For example, while a participant describes obedience as “always doing the right thing. Even if you're told otherwise” (Participant 31), another describes it as “following an order in a good manner and good attitude” (Participant 43).Obedience also evokes the theme of belonging to the nucleus. These elements are fundamental and stable components that form the central core of the representation, and represent the stability and unity of the SR. The first periphery, located in the upper right quadrant, is characterized by a high frequency of appearance and by a low average rank of appearance: these terms indicate the behavioral tendencies related to the SR . Moreover, it is an act against different types of authority (Level 2-coding) identified in parents or superiors. For example, one participant reported that disobedience is an act of being “disobedient to your parents, the police, to teachers, or even to God”iv (Participant 12). Participants identified different types of “orders” (Level 2-coding) with commands, rules, and laws (Level 1-coding) being the most cited. One participant reported how disobedience “is the lack of obedience or not obeying a rule, law, or an order” (Participant 52). Disobedience evokes the theme of failure (Level 2-coding), clearly observed in the participants’ tendency to define disobedience as “failing to obey certain laws to be followed” (Participant 46), “failure to abide by the rules, order, regulation” (Participant 6), and “failure to obey an authoritative figure” (Participant 73). Furthermore, participants reported that disobedience evokes an intentional behavior (Level 2-coding), as captured by some of the participants’ statements. For example participants defined disobedience as “intentionally going against what you are expected to do” (Participant 48), “blatant disrespect for the person who you are intentionally undermining” (Participant 62), and “voluntarily and purposefully violating a superiors orders” (Participant 76). Overall, disobedience was perceived as a negative behavior: “defined as misbehavior” (Participant 80), “doing the wrong things” (Participant 87), and “not doing the right thing or being negligent” (Participant 102).For the majority of the participants, disobedience was perceived as the refusal In analyzing the structure of the social representation of disobedience, see section "Obedience: Structure Analyses" above for the meaning of the quadrants.This section deals with the aggregation and the comparison between thematic and structural analysis of both obedience and disobedience. As previously stated by some structuralist scholars , only frrules and law confirm the necessity of an explicit form of order to evoke obedience. Social norms and laws  have a fundamental role in regulating human behavior in a variety of social contexts consciousness: a) a blind answer to a request, as destructive obedience , or b) aability, a positive skill a child should learn and act out during his or her lifespan. In fact, participants focused on obedience as the act of obeying figures such as parents and teachers, whom they follow in order to learn how to behave. Terms as family and religion reinforce this last statement and represent places where a child, as evoked in the nuclear elements of the representation, co-construct the SR of obedience. Since school, the military, and work, he or she learns obedience through socialization processes which are influenced by his or her cultural belonging , as the individual has to respect and be loyal to his or her commitments toward other people. According to this dimension, it is relevant to refer to Obedience also evokes the idea of respect (positive).Finally, the representation of obedience, obtained via merging content and structure, is largely considered as positive , because he or she does not respect other people and does not know how to behave in occasions where obedience is required, showing a lack of respect for social norms. Once again, we have concrete subjects of disobedience: children, animals and teenagers, revealing the conception of a one-to-one disobedience.Participants refer to commands in different ways along a continuum, going from very formal laws to verbal, more informal orders. Disobedience evokes the concept of intentionality. For the participants in the current study, disobedience is always an intentional behavior. This point seems to contradict the idea of disobedience as failure, because it considers disobedience as a planned and conscious act. This is an issue that accompanied disobedience since its first theorizations , or implicit orders such as laws . Obviously, these representations share the need for real authority figures to give orders or to create laws. Different authorities express themselves through various channels to give orders. For instance, “institutional” authorities can create and establish laws that people must follow, while parents, to fulfill their role, can give verbal indications to their children.children, teenagers, and animals as the main subjects in an authority relationship, indicating a preference in configuring an authority relationship as a face-to-face (one-to-one) relationship. School as a place of obedience and disobedience focuses on children, but also on educative figures such as teachers, who should teach a child how to behave properly and that are to be obeyed. In fact, obedience evokes the concept of ability, something that a person should learn in his or her first stages of life. When a person fails in learning this ability, then disobedience likely stands out. Moreover, while obedience evokes compliance to social norms, there are no references for social or civil disobedience. Another strong difference emerges through the participants’ polarization in the assessment of obedience and disobedience. The former evokes exclusively positive terms and adjectives, while the latter seems to be represented as something negative, for its nature and consequences. These antinomies, represented by the couple ability-failure and positive-negative, remind us of the dialogical approach within the SRT  Social learning, social institutions such as family and school should teach obedience; 3) Awareness, a necessity to agree with the authority’s request, in opposition to blind obedience. Undoubtedly, family and school are the first contexts where a person experiences relationships with authorities and its limits  s limits . Parentss limits . A parens limits . Interess limits .respect to different types of norms and of institutional authorities. Here, obedience referred to norms that range on a continuum from oral  to written norms . Again, a basic requisite for obedient behavior is the explication of the order, whether it is oral or written  Disobedience as expression of autonomy; 3) Different types of orders convey disobedience; 4) Awareness, disobedience is always a chosen act; 5) Punishment, as a consequence of disobedience.The term “disobedience” evoked more themes and components than “obedience”. All the samples included the following themes in the social representation of disobedience: 1) Disobedience as autonomy has been largely debated within the literature, from the eteronomy-autonomy dichotomy  towards a person and as a failure (vs obedience as ability). Lastly, Italians evaluated disobedience according to the consequences of its implementation, while Americans considered it always negative.Disobedience evoked the theme of uperiors , as welluperiors . Italianometheus . One of ometheus . Similardisobey the traditional paradigm and methods used to inquire about obedience and disobedience (Social psychologists agree with the need to change the point of view on authority relationship, to bedience . In thisbedience  providesbedience . Insteadbedience . Accordibedience . This apSumming up, if these two phenomena define the relationship with the authority and if the relationship with the authority is a central theme in one’s adequate social life, it is relevant to explore the meanings attributed to these social objects. This process will enable an understanding of the possible dynamics elicited by the relationship with the authority, whether this is an individual, as presented by the participants of this study, or an institution .The present paper also responds to the claim of civil disobedience component within disobedience social representation in the U.S.Possible limitations of the current study include the use of a single instrument to evoke the social representations of obedience and disobedience. Even if this instrument is an effective, reliable, and time-saving tool to uncover social representations , interviAs a possible development, authority relationship has been highlighted as a central theme in the study of civic participation , a type


The human karyotype has been used as a mechanism for describing and detecting gross abnormalities in the genome for many decades. It is used both for routine diagnostic purposes and for research to further our understanding of the causes of disease. Despite these important applications there has been no rigorous computational representation of the karyotype; rather an informal, string-based representation is used, making it hard to check, organize and search data of this form. In this article, we describe our use of OWL, the Ontology Web Language, to generate a fully computational representation of the karyotype; the development of this ontology represents a significant advance from the traditional bioinformatics use for tagging and navigation and has necessitated the development of a new ontology development environment called Tawny-OWL.https://github.com/jaydchan/tawny-karyotype, under a LGPL License, Version 3.0.The Karyotype Ontology and associated Tawny-OWL source code is available on GitHub at  The genetic complement of organisms is carried on one or more chromosomes. These chromosomes have a characteristic organization and, in many cases, a characteristic cytogenetic appearance. The analysis of this appearance has been known to relate directly to the underlying genetics for many years and, in fact, before the mechanistic link between the two was well understood. It remains of vital diagnostic importance, as well as providing a key tool for a large research community.the International System for Human Cytogenetic Nomenclature . First published around the 1960s, this system has been updated regularly subsequently. Although unnamed in the specification, here we call a string following these conventions an Unsurprisingly, for a specification of this age the ISCN specification is informally defined. It does not define a computationally interpretable grammar nor is there a formal interpretation or underlying semantics. Similarly, the specification itself is not available in a computationally amenable or even an electronic format, meaning that is not even straight-forwardly searchable. As a result of this ISCN strings are difficult to parse, validate and query, especially for complicated ISCN strings . Representing this ontologically presents a practical barrier: most ontology tools are designed for a person to create most classes and, based on our requirements, the Karyotype Ontology would need to have over 800 classes. While many ontologies are larger than this, the Karyotype Ontology is highly repetitive, with most classes following a standard pattern; moreover, we wished to maintain the flexibility of changing the axiomatization of the Karyotype Ontology. All of this would have been challenging with existing tools.http://homepages.cs.ncl.ac.uk/phillip.lord/take-wing/take_wing.html).For all of these reasons, the Karyotype Ontology was built using a new tool, Tawny-OWL, that was motivated by this use case. Specifically, Tawny-OWL is an ontology development environment implemented as a Domain Specific Language (DSL) in the programming language Clojure. This provides the ontology developer with a simple syntax  as a partonomy, with some inheritance. We actually use properties called ‘isBandOf’; as we do not use an upper ontology, these are not related to a property with the name ‘part-of’. So, for example,HumanChromosome1Bandp35 is a HumanChromosome1p which is a band of HumanChromosome1 which is, itself a HumanAutosome, which is a HumanChromosome. The ‘open world’ semantics of OWL means that we also need to make explicit the disjointness between bands and chromosomes. This is done at several different levels to minimize the total number of disjoint axioms that need to be made: for example, HumanChromosome1 is disjoint with HumanChromosome2 but not HumanChromosomeX, as the sex chromosomes and autosomes are already disjoint. Likewise, bands are only directly disjoint from bands on the same chromosome arm.r and k character, respectively. The human karyotype has more visible bands at higher resolutions, and these need to be explicitly described (defoproperty seenAtResolution:domain h/HumanChromosomeBand :range Resolution) ))  This is syntactically very similar to the equivalent statements in Manchester Syntax which we show here for reference:Class: res: r300-bandSubClassOf:  res: Resolution    ObjectProperty: res: seenAtResolutionDomain:  hum: HumanChromosomeBand    Range:  res: Resolution    Class: res: is-300-bandEquivalentTo:  hum: HumanChromosomeBand    and (res: seenAtResolution    some res: r300-band)        FragileSite and the pattern function fragilesite which uses this class. In Clojure, we define functions using the reserved keyword defn and parameters are declared within the square brackets. fragilesite itself uses a second pattern which, in this case, expands to an OWL ‘some’ restriction.As well as the human chromosome structure, we model a large number of ‘features’ such as fragile sites, neocentromeres and ring chromosomes, all of which are defined in the ISCN. These are all associated with functions which can be used to define restrictions describing these features of chromosomes. For example, the statements in this listing define an ontology class, (defclass FragileSite)(defn fragilesite[n band] (direct-feature n (owl-and FragileSite (owl-some e/hasBreakPoint band)))) The main purpose of this use of a function is simply to provide additional syntax, which reduces the amount of typing but, as with the use of patterns defining the chromosome structure, it also provides a degree of abstraction, meaning the pattern could be updated.In a similar vein, we also model the ISCN events, describing changes that can happen to a chromosome. As with features, these are defined in pairs defining an OWL class and a pattern. For example, an addition of a band is implemented as follows:(defclass Addition)(defn addition-band[band] (owl-and   Addition(owl-some hasBreakPoint band)))  For events to be meaningful, we have to provide some start point to which these events can happen. We define these simply such that their composition is not explicitly either in terms of their chromosomes or chromosome bands. For example, the diploid karyotypes are defined as follows:(defclass k46_XN:super BaseKaryotype) (as-disjoint-subclassesk46_XN (defclass k46_XX) (defclass k46_XY)) named karyotypes associated either with biological conditions  or specific syndromes . These latter are taken from examples given in the ISCN—we have not encoded all the karyotypes simply because there are a very large number, but have sampled across most sections of the book. A set of karyotype kinds are also stated as defined classes, that can be used in conjunction with a computational reasoner as queries: for example, a structural or numerically abnormal karyotype (defined below).In order to create a Clojure symbol that was also legal in Manchester Syntax, the commas have been replaced with underscores. We also define haploid, triploid and tetraploid karyotypes, and a large number of )   (e/event nil  (e/deletion-chromosome  h/HumanChromosome))))   Taken together, this enables us to express karyotypes of arbitrary complexity. For example, consider the representation of the ISCN string 45, X,-Y that we saw in (defclass k45_X_-Y:super  (owl-some b/derivedFrom b/k46_XY)(e/deletion 1 h/HumanChromosomeY) This representation is clear and unambiguous and can be reasoned over; for example, it can be retrieved as a diploid, male karyotype with loss of the Y-chromosome.In the next section, we describe our testing strategy which ensures that this reasoning works as expected.The Karyotype Ontology is a relatively complex ontology, containing some rich axiomatization. This reason alone would make it sensible to test, to ensure that the ontology has been built correctly. There is, however, a more compelling reason in this case; our intention is that with the Karyotype Ontology it should be possible to query over a large number of karyotypes defined using this ontology, for those which fulfil a given set of criteria using computational reasoning. For this, we need to ensure that the ontology reasons correctly.This has been achieved through combination of the Clojure unit test framework, and Tawny-OWL’s interface to the computational reasoner HermiT. Tests are defined into two halves; first, we have picked a large number of the classes defined in the Karyotype Ontology for testing.is macro, found in Clojure’s testing framework, to make these assertions.For example, the following statements assert that Down syndrome is a diploid karyotype with an autosomal gain, and that 46, XY is NOT female. We do this using the (is(r/isuperclass? n/DownSyndrome  n/DiploidKaryotype))  )  ))   In addition, we have classified a large number of different example karyotypes from ISCN against 17 different defined classes . Writing all these tests by hand would have been long-winded so, instead, they are encoded in a spreadsheet, following a document-centric approach , since this band is between the two breakpoints, but only these since only 1p22 is between these two.No Order: Order is not represented.Enumeration: All the affected bands are explicitly stated in the model, using a Tawny-OWL pattern to expand from a start-point to an end-point.Sequence Pattern: This ontology design pattern  set. Despite not having formal support for ordering, there are a number of ways in which it can be achieved; we consider four possibilities here.a priori and may, anyway, vary between different extant reasoners or a single reasoner over time.These have different characteristics in terms of expressivity, ease of use and so forth. The most important characteristic, though, which is query/reasoning performance is almost impossible to predict https://github.com/jaydchan/tawny-karyotype-scaling). Results are shown in One interesting consequence of the pattern-driven approach used to develop the Karyotype Ontology is that it is possible to change the patterns and then regenerate the ontology. In short, we can test these four different possibilities. This was achieved by generating large numbers of random karyotypes, and then testing (see From these results, we can see that the reasoning performance of the Karyotype Ontology is entirely usable, at under a minute for 10 000 karyotypes, that further adding ordering information to the Karyotype Ontology does not add excessive time to the overall reasoning, and that all three different mechanisms for representation of order have acceptable performance. However, we note that the different representations scale differently and that the choice is dependent on the number of karyotypes being searched. While, we note that while we supported several axiomatizations to enable performance testing during development, it could also be used during deployment, as a mechanism for scaling a karyotype database.In this article, we have described the development of the Karyotype Ontology. This ontology provides the ability to describe the human karyotype. Its representation closely follows the ISCN standard and is strongly based upon it. We have followed this approach for a variety of reasons. It is obviously most familiar to biologists and clinicians who deal with this data. Most importantly, ISCN has been built up and refined over many years and contains a lot of knowledge, and is likely to be a good representation.derived from 46, XY. This definition means 45, X,-Y is male; Turners syndrome, although phenotypically female, can be reasoned neither to be male nor female since the Karyotype Ontology defines to be derived from 46, XN—we do not know which kind of chromosome it has lost; it would, of course, be possible to assert this knowledge, once it is clear what answer the community would expect.We have considered the possibility of building the Karyotype Ontology purely as a partonomy; that is a representation that describes the human karyotype on the basis of the chromosomes and chromosome bands that it has. Initially, we decided against this representation on the grounds of performance. However, there are subtler reasons why this is not appropriate. For example, the consider the karyotype 45, XO which manifests as Turners Syndrome; that it is has a single X-chromosome. Partonomically, this is identical to the karyotype 45, X,-Y which also has a single X-chromosome. However, the latter karyotype is of a cell-line that has lost a Y-chromosome, while the former is a congenital ‘loss’. We can only distinguish these two on the basis of their history. This example also illustrates a surprising use of reasoning within the ontology see . IntuitiThe Karyotype Ontology is also not an ontology in the realist mould . We neitIn addition to this, we have adopted a different development style from many others. This ontology provided us a use case for the Tawny-OWL library, which enables fully programmatic ontology development. This has allowed us to adopt most of the industry-standard practices and tools from software engineering including functional abstraction, repeatable builds and unit tests, as well as tools such as an IDEs, versioning and continuous integration. This also gives us the ability to change wholescale our axiomatization by changing our patterns. We have used this ability to test the performance impact of different axiomatizations; to our knowledge this is the first time, this form of large-scale performance testing has been used on a complete ontology.There are, of course, some limitations to the Karyotype Ontology. We believe that the semantics of the representation are a considerable improvement over the existing ISCN strings in terms of computational precision and formality and, further, the syntax is defined, parsable and works well with existing tooling; however, the current representation is too verbose and difficult to write to directly to take the place of these strings. We have developed a parser that will convert some ISCN strings into the Karyotype Ontology, but given the informal definition of ISCN this is obviously difficult and heuristic; in future, we hope to develop a formal string representation which can compile to the OWL representation, similar to the way that InCHI strings can be converted to a chemical structure.We also note that the Karyotype Ontology is currently specifically a representation of the human karyotype; it would require modification or extension for use with other organisms. Given the difference in representation between different communities, it is likely that only a few high-level terms would be sharable. However, the generalized methodology that we have developed would be applicable. In this sense, as well as providing the first highly computational representation of the human karyotype, we have also introduced a new methodology for ontology development, recasting ontologies from tools for tagging records to a tool for modelling a complex area of biology accurately, precisely and searchable. We expect that there are many further areas of biology where this will prove to be useful.This work was supported by the Engineering and Physical Sciences Research Council [EP/P50564X/1].Conflict of Interest: none declared.