Cancer is an increasingly important health problem in Africa. The number of cancer cases in this region could double, ranging between 700 000 and 1 600 000 new cases in 2030. The mortality rate is higher than 80% and is explained, mainly, by a lack of early detection, diagnostics and treatment resources. In Angola, about 7,000 patients die of cancer every year.Data were derived from open-ended interviews conducted in 2010-11 with health authorities, clinicians, nurses and Administration of Hospitals. According Angola epidemiological data, results of interviews and international published advocacy for cancer control we develop a potential strategy for its control. The objectives are to identify existing resources for cancer control and describe the needs thereto, in order to establish an oncological program to guide the development of Angola cancer control strategies.Malaria remains the leading cause of illness and death in Angola, and other communicable diseases remain a public health problem. However, 9 000 new cases of cancer are diagnosed each year.The most common types of cancer are: cancer of the cervix, breast, prostate, esophagus, stomach and head and neck, as well as cancers with infectious origin, such as Kaposi‘s sarcoma and liver and bladder cancer. The foundation for developing national cancer control strategies includes: oncological data; investment and training; identifying and removing barriers; guidance and protection of the patient. Angolan National Cancer Centre, Sagrada Esperança Clinic and Girassol Clinic are now developing a cancer program.Improving the economic situation of Angola creates conditions for an increase in life expectancy which in itself is associated with an increased risk of oncological diseases. On the other hand, infectious diseases, associated with the risk of malignant tumors, are endemic. Thus, an increase in patients with malignant disease is expected. A plan is therefore necessary to organize the response to this old but less visible nosologic situation. Low and middle income countries, that constitute the majority of African nations, have witnessed a 20% reduction in the per-capita global burden of disease (GBD) since 1990, due to a decrease in infectious/communicable diseases, malnutrition and neonatal illnesses [By contrast, in those same countries non-communicable diseases are rising and are now responsible for 50% of the GBD. In this group of non-communicable diseases, the most relevant in prevalence are cerebrovascular and malignant diseases .Africa has a complex demographic and epidemiological situation that defines the context of any health intervention: it has a very young population - 41% of which is under 15 years old-associated with a high fertility rate of 4.7 births per woman, but a growing number of Africans are now living beyond the age of 50 years. The UN estimates that people aged 60 years or more will make up almost 26% of the African population by 2050 . In adulAgyei-Mensah showed that the high rate of urbanization associated with very important discrepancies in wealth and increasing urban poverty numbers were associated with a double burden of diseases and epidemiological models. These include huge levels of infectious diseases as the main cause of illness and death, as well as an increasing number of chronic and non-communicable diseases, also leading to death and significant disability, and caused first by cardiovascular diseases but also by diabetes and cancer .Therefore, cancer is an increasingly important health problem in Africa. According to Dr. Luis Sambo, the WHO Regional Director for Africa, the number of cancer cases in the region could double, ranging between 700 000 and 1 600 000 new cases in 2030. The mortality rate is higher than 80% and is mainly explained by a lack of early detection, diagnostic and treatment resources . The mosOncologic diseases in Angola are still of minor importance, compared to infectious diseases, but their mortality rate is high. According to Globocan (2008) for Angola, cancer of the cervix is the most common, breast cancer being the second most common in females. In males, prostate cancer is the most prevalent, followed by hepatocellular carcinoma. Malignant tumors associated with HIV and with schistosomiasis are also relatively common , 7.The aim of this study is to identify existing resources for cancer control and describe the needs thereto, in order to establish an oncologic program to guide the development of cancer control strategies in Angola.The data, including information about nosologic issues and specific resources, were obtained from open-ended interviews to health authorities, clinicians, nurses and hospital administrations conducted in 2010 and 2011. A literature review specifically focused on “cancer in Angola” was performed. Citation indexes were searched in Embase and PubMed databases. Taking into account the epidemiological data published for Angola, associated with the results of the interviews and with the international rules published and advocated for cancer control in low and middle income countries, we were able to achieve sufficient knowledge to draw up a potential strategy for cancer control in Angola.Angola has just over 2200 doctors for about 16 million people with a life expectancy at birth of 47 years. Malaria remains the leading cause of illness and death, but its mortality rate is decreasing. HIV is another public health problem. The seroprevalence is 1.9% and about 20 new cases of HIV are detected every day. The Angolan State provides about 35 million dollars a year to combat this disease. Angola has five medical schools and there are several professional schools for nurses and other health professionals , 9.In Angola there are about 9000 new cases of cancer diagnosed each year, and there are 7000 deaths attributed yearly to this disease . In 2006® radiotherapy equipment, but it is not running yet. A network for data collection inside the country exists and sometimes acts as a referral service [The National Oncology Center in Luanda is the oldest public center for the treatment of cancer patients in Angola. It has doctors, nurses, technicians and diagnostic capabilities. It also has chemotherapy facilities and professionals with experience in chemotherapy. There is a Varian service .The Sagrada Esperança Clinic belongs to a public company named Endiama. In addition to imaging and laboratory facilities, this clinic also has pathology facilities and a unit for the diagnosis, treatment and monitoring of breast pathology, with multidisciplinary treatment decisions implemented. There are two training programs currently in progress: breast oncology for general practitioners and nurses, and a training program for urologists . This cl®), and Nuclear Medicine resources for which operational licenses are expected to be issued by the Atomic Energy Agency. This clinic has now started organizing this oncologic service and the first steps for cancer care have been taken.The Girassol Clinic belongs to the public company Sonangol. This clinic has the capacity for diagnostic imaging, as well as laboratory facilities. It also has a specifically built oncology service, with a dedicated ward, a day care hospital, a radiotherapy unit  accreditation .Cancer is already one of the leading causes of death in developing countries, including in Angola. The incidence of cancer in developing countries is growing because of improvements in the control of communicable diseases and the resulting increase in life expectancy . Only 5%On the other hand, facilities for the diagnosis and treatment of cancer in most developing countries are scarce. Thus, the primary objective is the construction of a coherent program in a relatively short time, in which health gains are observed in a consistent manner, without forgetting the fundamental measures of primary and secondary prevention. This program will consist of organizational aspects and staff training, and will require some investment.The strategy to combat the malignancy involves: investment and training; identification and removal of barriers; and guidance and protection of the patient, as described by Bridges et al. in the control of breast cancer .Any non-communicable disease control program, including cancer control, must be built, from the beginning, on a comprehensive strategy that should include prevention, promotion of healthy behaviors, adequate and timely diagnosis and corresponding multidisciplinary treatment. This can be achieved by addressing the weaknesses of the health systems as a whole, particularly those of the existing hospital system at all levels .The lack of appropriate resources for biopsies and limited training of doctors in the early detection of cancer are some of the constraints that impair the ability to have a clear picture of the epidemiology of cancer in Angola, and must be solved within the health system.The foundation of a cancer program includes the following tasks: organization, training, investment, health education and behavioral change.Keeping a Cancer Registry is a very important activity, because it allows assessment of the magnitude of the problem and is instrumental for the National Oncology Program in setting priorities and determining the resources which need to be allocated. The identification of the existing material and human resources also provide strategic information. The integration and cooperation between health facilities dedicated to the diagnosis and treatment of cancer is crucial to increase proficiency in this area, avoiding unnecessary duplications .The training of dedicated medical staff should be associated with the acquisition of proper equipment . A multiInvestment in diagnostic facilities, pathology, surgical capacities, chemotherapy, radiotherapy and palliative care resources is fundamental and necessary , 18.Cancer control must rely on health promoting activities and preventive interventions. It is known that at least in some cancers, behaviors such as smoking and heavy drinking are related to a higher risk of malignant transformation. It is also known that the best results in cancer treatment are achieved with early detection, and this notion should be transmitted and promoted among the population. Thus, breast and oral cavity self-examination, as well as cervical cytology, should be encouraged. The urologic observation should also be stimulated in case of specific symptoms or age related risks .As is advocated by Gueye SM, it is simply unethical to screen the population and not have the capabilities to offer treatment for the detected diseases . The occThe improving economic situation of Angola creates conditions for an increase in life expectancy, which in itself is associated with an increased risk of oncologic diseases. On the other hand, infectious diseases associated with the risk of malignant tumors are endemic. Thus, an increase in patients with malignant diseases is expected. It is therefore necessary to organize the response to this less visible nosologic situation.


Current health care systems are not optimally designed to meet the needs of our aging populations. First, the fragmentation of care often results in discontinuity of care that can undermine the quality of care provided. Second, patient involvement in care decisions is not sufficiently facilitated.To describe the development and the content of a program aimed at: (1) facilitating self-management and shared decision making by frail older people and informal caregivers, and (2) reducing fragmentation of care by improving collaboration among professionals involved in the care of frail older people through a combined multidisciplinary electronic health record (EHR) and personal health record (PHR).We used intervention mapping to systematically develop our program in six consecutive steps. Throughout this development, the target populations  were involved extensively through their participation in semi-structured interviews and working groups.We developed the Health and Welfare Information Portal (ZWIP), a personal, Internet-based conference table for multidisciplinary communication and information exchange for frail older people, their informal caregivers, and professionals. Further, we selected and developed methods for implementation of the program, which included an interdisciplinary educational course for professionals involved in the care of frail older people, and planned the evaluation of the program.This paper describes the successful development and the content of the ZWIP as well as the strategies developed for its implementation. Throughout the development, representatives of future users were involved extensively. Future studies will establish the effects of the ZWIP on self-management and shared decision making by frail older people as well as on collaboration among the professionals involved. Current health care systems are not optimally designed to meet the needs of our aging populations . First, Yet, the roles of patients and informal caregivers in our health care system are changing. Patients are now increasingly encouraged to become involved. There are several reasons for this. First, patients are involved in their care because it is they who make daily decisions about how they manage their disease  . Second,However, increased patient involvement may be difficult to achieve in a health care system that suffers from fragmentation because both patients and professionals may already be struggling to meet the complex demands placed on them by such a health care system. In a fragmented health care system, care for a single patient, especially care for a frail older patient , is often provided by multiple professionals who work in a variety of settings ,10,11. ATherefore, we developed a program aimed at: (1) facilitating self-management and shared decision making by frail older people, and (2) reducing fragmentation of care by enhancing collaboration among professionals involved in the care of frail older people through a multidisciplinary shared electronic health record (EHR) and personal health record (PHR). This paper describes the development of this program.The program, the Health and Welfare Information Portal (ZWIP), was initiated by ZOWEL NN, a collaborative of stakeholders in health care and welfare services, located in the city of Nijmegen, the Netherlands. The two main objectives for the program were: (1) to facilitate self-management and shared decision making by frail older people and their informal caregivers, and (2) to improve collaboration among professionals by enhancing and facilitating information sharing through a multidisciplinary shared EHR and PHR. Intervention mapping, a stepwise approach for the systematic development of theory- and evidence-informed interventions , was choFirst, we assembled a planning group to develop the intervention. This planning group included the project manager, the project leader (RM), two researchers (SR and MHu), two family physicians, a geriatrician, a nurse scientist experienced in intervention mapping (MHe), an information technology consultant, and a long-term care facility physician.This planning group analyzed the existing problems with self-management of frail older people and interprofessional collaboration in primary care. First, we performed a literature search for barriers to patient self-management and interprofessional collaboration. Second, we conducted semi-structured interviews at the homes of frail older people (n = 11) and informal caregivers (n = 11). They were invited to participate by their family physician or welfare organization and were purposively selected based on variation in living situation, socioeconomic position, and health and social problems. Interviewees were asked for their experiences with receiving information from health care and welfare professionals, informational continuity , and interprofessional collaboration. Third, we established two working groups. The first group consisted of health care and welfare professionals (n = 15) who were involved in the care of frail older people. They were recruited through their employing organizations and were financially compensated for their time investments. Members included family physicians (n = 3), primary care nurses (n = 3), geriatricians (n = 2), municipality workers (n = 2), social workers (n = 2), a long-term care facility physician (n = 1), a pharmacist (n = 1), and a psychologist (n = 1). The second working group consisted of older people (n = 2) and informal caregivers (n = 2), who were asked to participate by older people participating in the user panel of ZOWEL NN. Both groups were asked to discuss the problems they experienced with self-management of frail older people and collaboration among professionals and they were asked to review and comment on the results from the literature search, semi-structured interviews, and the other working group.Results of this needs assessment were integrated into a logic model. This model is derived from the Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation (PRECEDE) model ,17 that Based on the problem analysis, we defined performance objectives  for each target population. These performance objectives were then crossed in matrices with those determinants of behavior that were known to have a major influence on behavior and were amenable to change. On the crossings of performance objectives and determinants, change objectives were formulated . We designed these matrices for all target populations involved .We searched the literature for theories that were proven to be effective in changing the identified determinants or that were successfully used to enhance patient self-management or to promote collaboration among professionals. From these theories, we selected methods and strategies for our program. In this selection, we aimed for an optimal balance between the expected advances toward our program objectives and the investments required from the target populations.Requirements for the program components were defined in additional meetings of the working groups of professionals and older people and informal caregivers. Subsequently, members of the planning group started development of program components. These components were reviewed by the working group of professionals and by two additional working groups of frail older people in an iterative process involving several rounds of reviewing by the working groups, the working groups making suggestions for improvement, and members of the planning group making adjustments. In this process, development and reviewing coincided, each working group being presented with the latest version of the components at the time of their meeting. Final versions of the program components were tested in a small pilot study involving two frail older people, two informal caregivers, and seven professionals.A prerequisite for adoption and implementation of the program was met by the extensive involvement of the target population in its development and the commitment of the local collaborative of stakeholders in health care and welfare services. Further, implementation was facilitated by selecting implementation strategies that were tailored to the needs of each target population. Planning for sustainability was started early in the development of the program by searching for funding for incorporation of the program in everyday practice.In this final step, we designed a plan for the evaluation of the program. This involved an evaluation of the effects of the program as well as a process evaluation.An overview of the results of the needs assessment for self-management of frail older people is provided in the logic model shown in All Dutch citizens are registered with their own family physician, usually over an extended period of time. This family physician functions as a gatekeeper; hospital care and specialist care (except for emergency care) can only be accessed with a referral by a family physician.When patients need other health care or welfare services , they can generally choose between many providers offering these services.Funding of the Dutch health care system is organized by means of a compulsory social health insurance scheme.Frail older people, informal caregivers, professionals, and previous research reported problems with patient involvement in self-management. These problems related to frail older people and informal caregivers not performing the activities required, and professionals not encouraging or facilitating involvement.Identified behaviors of frail older people and informal caregivers that contributed to these problems included: (1) not adequately informing professionals about their health situation nor asking sufficient questions ,30, and Important contributing behaviors of professionals were (1) not providing the frail older person with adequate information for self-management ,26,34, aProfessionals, patients, informal caregivers, and the literature cited problems with collaboration among professionals. The main behaviors that contributed to these problems were a lack of communication or insufficient communication ,39,47; dBased on our needs assessment, we defined performance objectives for both program objectives and for each target population involved  and 2. ASocial cognitive theory  was seleTaking the former steps of the intervention mapping process into account, we developed the main component of the program: the ZWIP. The ZWIP is a personal, Internet-based conference table for multidisciplinary communication and information exchange for frail older people, their informal caregivers, and professionals. It can be considered to be both a shared EHR and PHR. The ZWIP is aimed at frail older people identified through a specific screening method and includes: (1) a tool for multidisciplinary communication in a secure environment that enables communication through sending messages between the frail older person, informal caregiver, and the professionals involved; (2) an overview of health care and welfare professionals involved in the care of the frail older person and their contact information; (3) information about the frail older person’s health, functioning, and social situation as well as the care provided; (4) the goals and action plans of the frail older person and the informal caregiver, which are formulated with them during home visits by nurses or social workers by means of a goal-setting tool; and (5) tailored educational materials for the frail older person and informal caregiver. Fundamental to the ZWIP is the central position of the frail older person, who can view the information included and who decides which professionals are granted access to his personal ZWIP. As a rule, messages that are communicated within the ZWIP are visible for all professionals with access to the ZWIP as well as for the frail older person and informal caregiver. This allows everyone concerned to remain informed about the frail older person’s situation and enables everyone to bring up their own relevant observations in an ongoing conversation. However, at the request of frail older people and professionals, we also included the option of sending a private message to an individual person.After development, as a final step before implementation, we conducted a small pilot study of the ZWIP. The most important lessons learned from this pilot were practical issues such as the need to communicate as unambiguously as possible.Strategies used for the adoption and implementation of the program were tailored to the needs of each particular target population. We will describe the main strategies used in the next paragraphs; an overview of all strategies is provided in For health care and welfare professionals, our most important strategy was an interdisciplinary educational program for health care and welfare professionals involved in the care of frail older people. This program consisted of 3 three-hour meetings concerning the following subjects: (1) the concept of frailty and identification of frailty, as this was required to identify the frail older people who were the program’s target population; (2) providing self-management support to frail older people by thoroughly informing them and using collaborative goal setting; (3) interdisciplinary collaboration, including information about what each discipline has to offer in the care for frail older people; and (4) working with the ZWIP. Except for its educational content, the educational program also served as a method for identifying and bringing together local health care and welfare professionals involved in the care of frail older people because the program enabled professionals to get acquainted with each other. The educational meetings were held near local family practices and all local professionals working with frail older people were invited to participate. Another important strategy was that we aimed to ensure the participation of intrinsically motivated early adopters. Further, we tailored the implementation of the program to each setting by providing family medical practices with several options for implementation, which allowed them to choose the method that would best meet their local needs and circumstances. Also, we provided financial compensation for time invested in the program, gave coaching and e-coaching in using the ZWIP, and had a telephonic help desk available.For frail older people and informal caregivers, we had two main strategies. First, we involved their family physician in the project, who actively promoted their participation. Second, we aimed to either facilitate the use of information technology or to make the use of information technology by frail older people redundant, as we were aware that they often have low computer literacy. Hence, we provided them with an Internet-based version of the ZWIP as well as a paper version of the ZWIP, which held all information that was included in the Internet-based ZWIP except for the communication; we offered them a home visit by a volunteer, who could either demonstrate the ZWIP to inform them about its possibilities or could train them in using the ZWIP themselves; and we had a telephonic help desk available during office hours.As a final step in the intervention mapping process, we planned the evaluation of the ZWIP. This evaluation will involve both a process evaluation and an effect evaluation. In the process evaluation, we will evaluate the implementation of the intervention, exposure of the target populations to the intervention, experiences of the target populations with the intervention, and barriers and facilitators to the use of the intervention. This will be studied using a combination of quantitative and qualitative data . The effects of the ZWIP program will be evaluated by means of a controlled clinical trial. Outcome measures will be the effects of the program on interprofessional collaboration, patient self-management and autonomy, patient outcomes such as functioning and quality of life, and use of care. Also, cost-effectiveness of the ZWIP will be evaluated. Last, as we consider the interprofessional educational program an important part of the implementation, the effects of this program on interprofessional collaboration will be evaluated separately. This will be done in a before-and-after study using several validated questionnaires (ie, the Attitudes Toward Health Care Teams Scale , the IntThis paper describes the successful development of a program aimed at facilitating self-management and shared decision making by frail older people and their informal caregivers and at reducing fragmentation of care through improving collaboration among professionals. For this development, the intervention mapping framework was used and future users were involved extensively. In the past, this framework has also been successfully used for the development of health promotion programs aimed at such diverse topics as leg ulcers , physicaA major advantage of the use of intervention mapping was that it facilitated the systematic incorporation of the needs and preferences of the target population as well as evidence from previous research. We can exemplify this with our first program objective, which concerned self-management and shared decision making. Previous research has shown that most older people prefer a less active role in medical decision making , but theFurther, the program benefitted from the involvement of the target populations because they brought up a wide range of knowledge and perspectives . MoreoveAlthough involvement of the target population was considered important, it also presented a challenge. First, involving frail older people proved to be difficult. For the limited number of frail participants in the working groups, problems such as not being able to attend the meetings due to health problems limited their ability to participate. Therefore, we also invited older people who were not frail to join the working groups. Also, for some of the frail older people participating in the semi-structured interviews, cognitive problems made it difficult for them to express their views about the rather abstract interview topics. Therefore, although frail older people were involved in the development process, their involvement was less than we would have preferred. Second, the evidence gathered from previous research and the different working groups did not always point in the same direction. An example was the discussion about whether or not all messages should be visible to everyone with access to the ZWIP. The working group of professionals was hesitant at first to make all messages visible, and the working groups of frail older people were divided. In the end, both groups mentioned that there were instances in which they felt a private message was absolutely required. In such cases, the planning group made a final decision. These decisions were made based on a thorough deliberation on all the arguments available from the literature and the working groups as well as arguments concerning feasibility.Although the ZWIP is a systematically developed evidence-informed intervention, its future success depends highly on its successful implementation and its use by professionals in everyday practice. Implementation and use will be monitored and adaptations will be made whenever required. Further, future use of the ZWIP in everyday practice will have to establish the added value of the communication tool of ZWIP in relation to already existing communication methods.In summary, this article describes the successful development of the ZWIP, a personal, Internet-based conference table for multidisciplinary communication and information exchange for frail older people, their informal caregivers, and professionals. We expect that the ZWIP will be able to increase the involvement of frail older people and informal caregivers in their care and will improve collaboration among professionals. Therefore, we expect that the ZWIP will contribute to filling the gaps in our fragmented health care systems.


About 10-20% of Familial Mediterranean Fever (FMF) patients do not achieve complete remission, due to colchicine resistance or sensitivity. Disease control in these patients is still an unmet challenge. Case reports and a small case control study, suggest a role for interleukin 1 beta blockage, particularly anakinra, in the management of this limitation of colchicines.To embark on a study, evaluating the efficacy and safety of anakinra in the treatment of colchicine refractory FMF.We plan to include patients, agreeing with clinical and genetic diagnosis of FMF, who suffer from FMF attacks, at least once per month, in one of the sites commonly involved by FMF , despite treatment with colchicine 2 mg/day or less (in case of colchicine intolerance). Involvement with other diseases relevant , or irrelevant , to FMF, or possible non compliance, will serve as exclusion criteria. The study is planned to continue for 4 months per patient, in which patients will receive anakinra , or control drug . Randomization will be sequential for a predetermined order of the interventional drug (anakinra or vehicle), for which the study team will be blinded. Analysis of the results will be performed by an external company. Anakinra effect will be compared to placebo effect by computing the reduction of number of attacks per each patient. Secondary outcome include reduction of severity of attacks.No results are yet available. The study is an investigator initiative project, with sponsorship of the manufacturing drug company. Measurements were taken to avoid any bias in the performance of the study or interpretation of the results. It is expected that the whole study will continue 2 years.A favorable anakinra effect in the prevention of FMF attacks in colchicine failure, supported by ample case reports is expected to be confirmed by the present controlled double blinded study by mid 2015.None declared.


Epilepsy is a prototypical, stigmatised disorder. Numerous studies have been conducted regarding the public perception of epilepsy, but they are primarily from high-income western countries; few studies have taken place in low- to middle-income countries with a traditional culture and a religious orientation.The public knowledge and attitudes towards epilepsy in Tehran, Iran, is studied.A survey of 800 subjects ranging from 18 to 85 years was randomly chosen from households in Tehran in 2009. The questionnaire used was based on the Caveness and Gallup's studies conducted in the United States in 1949 and it has been used in numerous similar studies all over the world. The mean age of the participants was 37.5 years and 46.7% were female. Pearson's Chi-squared test was used for subgroup analyses.The majority of subjects cited brain disorders as a cause of epilepsy, while 17% indicated the will of God as the cause. Most individuals were willing to work with a person with epilepsy, allow their children to play with a child with epilepsy, and allow people with epilepsy to use public transportation (78–82%). However, only 28% were willing to accept the marriage of a family member to someone with epilepsy.The knowledge and attitudes towards epilepsy are similar to those in Europe, with the exception of a much lower acceptance regarding marriage to a person with epilepsy. However, the low acceptance for marrying someone with epilepsy reveals the remaining misconceptions about the nature of epilepsy in Iran, despite the high educational level in the studied population. Therefore, informational efforts must be employed to change the perception of epilepsy. In nIn high-income countries with modern treatment facilities and a more educated public, the problems caused by the stigmatisation of epilepsy have decreased . In low-The first studies on the public awareness and attitudes towards epilepsy were performed in the United States in 1949 by Caveness and Gallup . They deA number of studies have been conducted in Islamic countries. A study by Bener et al. from the United Arab Emirates showed a rather high awareness of epilepsy, but 40% believed that faith healing is the proper treatment. A small percentage (7%) objected to allowing their children to play with children with epilepsy, but up to 68% objected to their children marrying a person suffering from epilepsy . The samPeople suffering from epilepsy were historically considered to have a changed personality; they were considered to be unstable, explosive, hypochondriacs, and clingy . A commoThis study investigated the public knowledge and attitudes towards epilepsy in Tehran, Iran.The greater Tehran area contains nearly 12 million inhabitants . Tehran A questionnaire was delivered by four trained psychologists from the university – two male and two female. One person per household was asked to fill out the questionnaire. The investigators waited while the questionnaire was completed to offer help if there were any questions. The investigators approached the families on weekday mornings and afternoons, as well as on holidays, to obtain representative samples. The data collection occurred from April to December in 2009.The questionnaire addresses socio-demographic background data, age, education, marital status, and occupation, and includes 14 questions regarding the knowledge and attitude towards people suffering from epilepsy and one open-ended question regarding the cause of epilepsy. This set of questions has been used in several studies worldwide, and it is based on the original study by Caveness in the United States .The questionnaire was translated into Farsi from the English version through translation and back-translation by psychiatrists and neurologists knowledgeable in English.The project was approved by the ethics committee of the Medical School of the Tehran University of Medical Sciences. The study was conducted in accordance with the Helsinki declaration on research ethics. Participation was voluntary, and the responses were anonymous.The data were analysed using the SPSS v 13 software. The frequency distribution was calculated, and Pearson's Chi-squared test was used for subgroup analysis. Variables were considered significant at the 0.05 level.The socio-demographic background data for the population are presented in The subjects’ knowledge about epilepsy is presented in One question was about words used for epilepsy; in Farsi, Arabic, and the Turkish language, epilepsy is called ‘Saraa,’ meaning ‘being knocked down.’ Other mentioned words included ‘Taashanog,’ which means ‘moving attack,’ and ‘Ghash,’ which means ‘suddenly falling (knocked) down.’Regarding the causes of epilepsy , the majThe attitudes towards epilepsy are presented in There were significant gender differences regarding the willingness to employ or work with someone with epilepsy and to allow their child to play with a child with epilepsy. The women were more willing to allow their child to play with a child with epilepsy (87.2 vs. 78.4% for men).Subjects with more education were generally more accepting towards employing someone with epilepsy, allowing their child to play with a child with epilepsy and allowing a person with epilepsy to use public transportation. However, when accepting someone in the family to marry somebody with epilepsy, there was no significant difference regarding gender or educational level. Interestingly, the oldest group (>65 years) was significantly more accepting than the youngest group (43.5 vs. 25.8%). Conversely, the elderly group was the most likely to hide the fact that someone has epilepsy.The general knowledge about epilepsy seems to be good in this sample, and the views regarding the causes of epilepsy indicate a fairly knowledgeable population. The vast majority cited a brain disease as a cause of epilepsy 62.2%). More than half of the population provided two or more alternatives, indicating that the subjects have a differentiated view on the possible background. Moreover, 17% cited the will of God, and none blamed evil spirits. This result contrasts with that found in Muslim countries in Africa and other parts of Asia where the idea of evil forces is prevalent 2.2%. Mor–20.This last result is interesting and is shared with many populations all over the world. What causes this hesitation to include a person with epilepsy into a family? In many countries, even in the west, there were legal prohibitions against marriage until the middle of the 20th century. One reason may be that people think that epilepsy is hereditary; this prohibition was intended to prevent the spread of the bad ‘genes’ to new individuals. Another reason might be that people with epilepsy are strongly stigmatised, making it shameful to include such a person in a family. This attitude also reflects the importance of family and the effort to protect the family from unwanted, marginalised elements, particularly in the traditional, collectivistic culture found in places such as the Islamic Republic of Iran.When studying the experience of stigma by people with epilepsy in Tehran, Iran, many individuals experienced stigma and discrimination because they suffered from epilepsy . SpecifiIn general, different approaches have been suggested to combat stigma and discrimination against epilepsy , 8, 13. The studied population is representative of the general population in Tehran, including the rapidly growing and well-educated middle class in Iran. The questions used in this study have been used all over the world for many years to study the public awareness and attitudes towards epilepsy, making these a well-established tool. The small differences observed in the proportion of males and females are not particularly important in the results. The majority of the females are unemployed/housewives, reflecting the socio-cultural milieu in Iran.The knowledge and attitudes towards epilepsy are similar to those found in studies conducted in high-income western countries, with the exception of the lower acceptance of a person with epilepsy marrying into the family. Therefore, the perception of epilepsy must be changed in Iran. Although people seem to be well informed about the nature of epilepsy, informational campaigns might help change the perception of epilepsy because modern treatment has considerably decreased its medical and social consequences. Possible actors in this would be the Iran Epilepsy Association in collaboration with the Ministry of Health, professional organisations, and media profiting from the experiences of the WHO campaign against stigma because of epilepsy.


In South Africa, providers are trained on post-rape care by a multitude of organisations, resulting in varied knowledge and skills. In 2007, a national training curriculum was developed and piloted in the country. The objectives of this paper are to identify the factors associated with higher knowledge and confidence in providers at the commencement of the training and to reflect on the implications of this for training and other efforts being made to improve services.A cross-sectional study using questionnaires was conducted. Providers who attended the training provided information on socio-demographic background, service provision, training, attitudes, and confidence. Knowledge was measured through multiple choice questions. Bi-variable analysis was carried out in order to test for factors associated with high knowledge and confidence. Variables with a p value of <0.20 were then included in backward selection to develop the final multivariable models.Of the 124 providers, 70% were female and 68% were nurses. The mean age of the providers was 41.7 (24 – 64) years. About 60% of providers were trained in providing post-rape care. The median percentage knowledge score was 37.3% (0% - 65.3%) and the median percentage confidence score was 75.4% (10% - 100%). Having a more appropriate attitude towards rape was associated with higher knowledge, while older providers and nurses had lower odds of having high knowledge levels. Working in a crisis centre in the facility, having examined a survivor in the last 3 months, and seeing more than 60% of survivors who came to the facility were associated with higher confidence. Higher confidence was not associated with greater knowledge.The study indicated that although confidence was high, there was poor knowledge in providers, even in those who were previously trained. Knowledge seems to be critically dependant on attitude, which highlights the need for educating providers on rape and the seriousness of the problem. There is a need to train more providers in post-rape care in country, and to ensure that training is comprehensive, and that providers who are trained remain knowledgeable and skilled in current best practices. In South Africa, the majority of rape survivors are cared for in the public sector at primary health care level. Post-rape care should be provided by trained doctors and nurses , yet stuThe National Department of Health aimed to use the curriculum to equip doctors and nurses to comprehensively provide post-rape care. The curriculum was developed by a number of local experts under the coordination of the Gender and Health Research Unit of the Medical Research Council. This work was based on reviews of both national and international training programmes. The newly developed curriculum finally comprised of ten days of interactive training and a one day practicum, covering all aspects of post-rape care including epidemiology, human and sexual rights, communication, medical management of the survivor, examination and evidence collection, follow-up care, laws and court procedures, monitoring and evaluation of services, and vicarious trauma. Vicarious trauma is known as compassion fatigue that is felt by providers who work with traumatized patients and can potentially affect the physical and mental well-being of the provider . The curIn developing the curriculum, a number of issues came to the forefront. Firstly, what is the current knowledge and confidence of health providers working in post-rape care and would the curriculum improve this, what are the factors that influence knowledge, confidence and care offered by providers, and finally, which providers should we be training to work in post-rape care services?A review of international post-rape training programmes showed that there were marked differences in the courses offered to providers -16, withVery few studies have looked at the providers working in post-rape services. A review of the SANE programmes has shown some positive findings with SANEs providing more comprehensive care and examinations than what was traditionally provided by the hospital emergency department ,17, thatThe objectives of this paper are thus to identify the factors associated with higher knowledge and confidence in health care providers working in post-rape care services at the commencement of training and to reflect on the implications of this for training and other efforts being made to improve services.A cross-sectional study was undertaken with data collected during four training sessions that were held from February to May 2008. One hundred and fifty-two providers from eight provinces attended the training. The Western Cape provincial Department of Health declined to participate in the study. Health care providers who were selected by provincial managers to attend the training were either doctors who had completed internship or professional nurses with midwifery qualifications. All providers had some previous exposure to post-rape care services.Providers who underwent the pilot training completed self-administered questionnaires. These had questions on social and demographic characteristics, the manner in which rape services were provided, the workload in relation to post-rape care services, prior training on counselling and post-rape care services, confidence in providing post-rape care, gender attitudes, attitudes about issues related to rape, and levels of empathy. The questionnaire made use of questions that had previously been tested in research conducted by the Gender and Health Research Unit, including an instrument used in a situation analysis of sexual assault services (1), and a questionnaire used in a survey of men’s health and relationships (11). For the purposes of this study, only data from the questionnaires completed prior to the interactive training component are presented.Socio-demographic and background information was collected on sex, age, rank, and the province where the health care provider was working, the type of facility where they were working, and the number of years they had been working in total and at the current facility. Data was also collected on the proportion of rape survivors seen by the provider and whether the provider had seen a rape survivor and completed the necessary legal documentation (J88 form) in the last three months. Information on where undergraduate training occurred and whether the provider received further training on post-rape care and counseling was obtained.A rape attitude score  based on 21 statements  was obtaet al.[An empathy score  was also calculated using four statements, that were adapted from work done by Abbey et al.. These hMen were also asked about perpetration, and women about experience, of intimate partner violence using a version of the WHO violence against women instrument (12). This had been adapted for use with men in the Eastern Cape . It included two questions related to physical abuse, one to emotional abuse, and four to sexual abuse. For example, female providers were asked about being slapped, pushed, shoved, hit, kicked or having something thrown at them by a partner. They were also asked about whether a partner had ever threatened to hurt them or use a weapon against them. They were then asked about whether they had ever been tricked into having sex with a man, whether they had ever agreed to have sex with a man after he told lies, threatened to end the relationship, or pleaded; whether they had ever had sex when they had not consented or were forced, and whether they had ever slept with a man or boy when they were too drunk to say whether they wanted to or not.Knowledge was assessed using 75 multiple choice questions covering the various aspects of post-rape care. These covered all aspects of the curriculum material and were developed and reviewed by staff at the Gender and Health Research Unit. The questions were piloted on a group of ten medical doctors, after which some changes were made. In addition, nine questions that had a particularly high failure rate through all pilot sessions were excluded from the final data analysis, resulting in a total of 66 questions.Health care providers reported on their confidence in providing ten aspects of post-rape services, using a score of 1 to indicate ‘no confidence’ and 10 to indicate ‘total confidence’ in providing the service. Questions covered examination, evidence collection, and appearing in court. Both the knowledge and confidence scores were converted into percentages and categorized. Providers with a percentage score of 50 or more were considered to have high levels of knowledge and those with a percentage score of 80 or more were considered to have high levels of confidence. These cut points were based on the mean scores for knowledge and confidence levels.Data was entered and analysed using Stata 10. Descriptive statistics were first conducted on the baseline characteristics of the health care providers in terms of background, experience, knowledge and confidence, after which bi-variable analysis was carried out in order to test for factors associated with high knowledge and confidence separately. Variables with a p value of <0.20 were included in the candidate models and backward selection was used to develop the two final multivariable models on factors associated with high knowledge and confidence. In the final models, variables were retained with a p value of less than or equal to 0.05.Ethics approval was obtained from the Human Research Ethics Committee:  of the University of the Witwatersrand . The health care providers were given an information sheet and were asked to sign informed consent when they returned the completed questionnaire. Participation in the study was thus optional and utmost care was taken to ensure that the anonymity of the study participants was maintained.In total, 124 health care providers (81.6% of those trained) completed pre-training questionnaires. The mean age of the providers was 41.7 years with a range from 24 to 64 years. The majority of providers trained were female (70.2%) and professional nurses (68.3%). Of the 39 doctors who were trained, six were completing their community service year, which is a compulsory second year of working in the public sector after completion of medical school  of providers were working at the primary health care level   and those who had examined a survivor and completed a J88 in the last three months  had a greater odds of having higher levels of confidence. Providers who had seen more than 60% of survivors who came to the facility were also found to have greater odds of having high confidence compared to providers who had seen less than 20% of survivors . Previous training was not found to be associated with higher knowledge or confidence levels. Furthermore, levels of knowledge were not associated with confidence levels .The training programme included a range of providers from junior staff to those who were experienced. Yet there were still substantial gaps in the knowledge of providers and many providers were not completely confident in delivering every aspect of post-rape care. The study also found that providers who were previously trained did not have significantly greater levels of knowledge and confidence, but that confidence levels were disproportionately higher than levels of knowledge in all of the providers. This could be related to the manner in which training was offered in the country through a piecemeal approach, with poor or absent content, giving providers a sense of assurance in providing service yet in fact not improving knowledge on post-rape care.In addition to levels of knowledge, provider attitudes when delivering services are important for patients ,19. InteWorking in a facility with a crisis centre and being involved in the care of survivors was found to be significantly associated with higher levels of confidence. It has been reported that the experience of working with the same types of patients improves clinical skills  and therHowever, it is still a matter of some concern that many providers do not have adequate levels of knowledge. Providers who had worked for more than 15 years in the same facility were found to have low levels of knowledge and similarly, older providers had a lower odds of having high knowledge levels. This indicates the need for continuous training and development of providers during the in-service period. There is a risk that providers become complacent and if they are not informed of current updates in the literature over time, they may not change their practices. As this discipline is constantly changing and new practices are being developed based on current evidence, there is always a need for continuous professional updates. Nurses were also found to have a lower odds of having high knowledge levels, and this is reflective of the current health service organization in South Africa, where the role of nurses in the provision of post-rape care has not been adequately defined. Thus nurses tend to receive minimal training and in most areas are only involved peripherally in the provision of post-rape care.A high percentage of providers had experienced violence as victims or perpetrators, and startlingly a third of male providers had committed rape themselves. This highlights the importance of being extremely watchful for vicarious trauma, as affected providers are particularly vulnerable. There is also a need to understand the impact of having perpetrated violence against women on the care provided by male providers. This could be manifested through the provision of poor quality care with a lack of empathy, or could result in emotional problems for the provider through having to provide care for survivors. Exploration of this aspect was limited by the small sample size.The generalizability of the findings in this study is limited, as some of the providers of the training were selected because they were known to be experts who would themselves later train, and this may have resulted in a bias towards a more knowledgable and confident group. The Western Cape Department of Health declined to participate in the pilot study and therefore there were no providers from this province included in the study. Some of the data were sensitive in nature but the questionnaires were self-administered to limit underreporting and ensure confidentiality. There was also a potential for recall bias. The knowledge and confidence measures were developed and used for the first time in this study. Although piloted on a small group of doctors prior to the study, these measures still need to be further assessed for reliability. Nine questions that were found to produce high levels of failure were dropped from the knowledge score. Providers did not respond to all questions in the questionnaire and this resulted in missing data for some of the variables. Providers were only asked about their provincial location and therefore no distinction can be made between providers working in urban and rural settings within the provinces. The small sample size limited further analysis of the data, for example, by sex of the doctors.The study indicates that there were gaps in knowledge even in providers who had been previously trained and that, although confidence was generally high, there were very poor levels of knowledge. A comprehensive standardized training curriculum for post-rape care services was undoubtedly needed in the country. It is clear that if the objectives of the National Sexual Assault Policy  and The CHC: Community health centre; CI: Confidence interval; IPV: Interpersonal violence; OR: Odds ratio; SA: South Africa; SANE: Sexual assault nurse examiner; USA: United States of America.The authors declare that they have no competing interests.RJ, RJ and NC were involved in the conceptualization and design of the study and the development of the data collection tools. LL and RJ were responsible for the collection and entry of data. RJ and RJ analysed the data and drafted the manuscript. All authors read, and approved the final manuscript.RuxanaJ is a public health medicine specialist at School of Public Health, University of the Witwatersrand. RuxanaJ has an interest in women’s health, focusing specifically on gender-based violence and health. RachelJ is trained as a public health physician, epidemiologist and qualitative researcher. She is the Director of the Gender and Health unit at the Medical Research Council and Secretary of the global Sexual Violence Research Initiative. NC is a senior lecturer and coordinator of the Masters of Public Health programmes at the School of Public Health, University of the Witwatersrand. NC holds a PhD from the Rollins School of Public Health, Emory University. Over the last ten years, NC has worked on the development of gender-based violence services through policy formulation and research. LL is researcher at the Sexual Violence Research Initiative, hosted by the South African Medical Research Council. She holds a Masters Degree in Sociology with Specialization in Gender Studies.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/257/prepubTable S2. Experience and training backgrounds of health care providers. Table S3. Knowledge by topic. Table S4. Regression models for factors associated with knowledge and confidence.Demographic and other background of health care providers. Click here for file


Life is a specific characteristic of our planet. The diversity of life, biodiversity, is one of the most fascinating phenomena. We know some 1.8 million different species, but all extrapolations show that probably 20 million or more species exist: We know less than 10% of the plants, animals and micro-organisms living on the planet Earth. The editors, who are both biologists, are well acquainted with these figures whilst for non-biologists this fact is most surprising and even unbelievable. The process of life started more than one billion years ago, it is a continuous process of evolution, of mutation and selection, of structures and materials. Put another way, this means one billion years of trial, error and optimization. The diversity of life thus created a breath taking diversity of materials and structures based on an extremely restricted number of elements.It took a surprisingly long time until we understood what we can learn from one billion years of biological development work. No doubt, Daedalus and Icarus in Greek mythology copied biological models – without, however, great success. This is an unbroken tradition from past epochs to the era of Leonardo da Vinci up to the present day. However, systematic research of biological systems for a technical application began astonishingly quite late: Bionics and biomimetics became important only after 1960, and it was only in the new millennium they became worldwide disciplines with high potentials for innovation. An apparently simple observation can lead to new materials, structures and design principles, but the technical transformation and realization may take a much longer time. Our own example of the self cleansing abilities of lotus leaves clearly demonstrates this point: Published for the first time in 1976, patented as a technical feasibility in 1994, facade paints only appeared on the market in 1999.Biomimetic materials.Bionics concentrated in the first decades, in particular, on highly complex biomechanic problems: the hovering of humming birds and robot locomotion. Today a focal point is the incredibly specific diversity of biological materials, materials with micro and nano structures, often self-assembling. Another change of paradigm was caused by lotus leaves: surfaces and boundary layers. All interactions between an organism and its environment take place via its surface – be it the interaction between a solid , a liquid , a gas  and radiation . Boundary layers and, in particular, superhydrophobic surfaces and their interactions with the environment were thus the focus of this Thematic Series on The most interesting phenomena happen on boundary layers: from the biosphere at the boundary layer of our planet down to the surfaces of lotus leaves or Salvinia water ferns. And these are only two out of the 20 million species which all have secrets to be revealed: Biomimetic materials provide innovative solutions for the design of a new generation of bio inspired functional materials.Wilhelm Barthlott and Kerstin KochBonn, Kleve, March 2011


Aim: The purpose of this article is to analyze and validate the CR-POSSUM score in patients with peritonitis of colonic origin, considering mortality forecasting ability.  Methods: We conducted a prospective longitudinal study of the Surgery Clinic in the Emergency Hospital in Bucharest in January 2008-December 2011. Patients operated on for peritonitis of colonic origin were included in this study. The prognostic CR-POSSUM scores and Mannheim peritonitis index were calculated by using data from observation sheets. There have been a number of deaths and overall mortality was calculated.  Results: There were 58 patients with abdominal sepsis, hospitalized and operated, registering a 17.24% mortality rate. Time from admission until the time of operation was divided between up to 24 hours and over 24 hours, recording 27 (46.55%) cases operated <24 hours and 31  of patients operated> for 24 hours. Operative severity scores were calculated by taking into account data provided by each surgeon on intraoperative appearance.  Conclusions: The results of this study demonstrated that both CR-POSSUM score and Mannheim have a prognostic value for patients with abdominal sepsis in colonic peritonitis, both being surgery scores. The ideal score for complete surgical evaluation should assess both morbidity and mortality. It should also be quick and easy to use and apply to all types of surgery, both emergency and elective. Also the scoring system must be easily implemented in the existing assessment programs.  The literature describes numerous scoring systems that predict the mortality risk, but does not analyze postoperative morbidity. Some scores have been developed and are useful for certain types of surgery, others are used to assess the mortality risk and a little morbidity in certain groups of patients and the scoring system assesses the risk of developing complications.  When comparing the quality of care, morbidity and mortality rates have obvious limitations and false negative results may occur because the physiological state of the patient at the time of surgery, the complexity of the surgery, the patient's health status, age, etc., are elements which are not taken into account.  The scoring system is described; which has reduced the number of variables in order to facilitate scoring system, but this reduction certainly has some disadvantages. 1] developed a scoring system using 12 variables and showed that any reduction in the number of variables below, will affect the predictability of mortality and morbidity. This scoring system makes a prediction of morbidity and mortality for patients in general may be differences between groups of patients according to a certain type of surgery.  Starting from this premise, Copeland et al. . Over-prediction of mortality can be explained in part by the characteristics of mathematical scoring system (e.g. young patients undergoing elective interventions). Another possible explanation could be the existence of differences between subjects. There are patients who have a high degree of disease, and this has important implications in the development of the score. The results of this analysis are somewhat different from some previously published studies [7]. In addition, it is possible that CR-POSSUM is overstated in elderly patients with preexisting comorbidities. The study group meets thus the situation for patients aged between 71 and 80 years. This situation is similar to that described by Slim et al. [8] who studied risk prediction score POSSUM and index AFC (Association Française Surgery). Patients with advanced colon cancer had an important nutritional deficiency. Malnutrition due to decreased nutritional intake, malfunctioning metabolic processes, hormonal abnormalities and related cytokines are the main causes of severe sepsis in cancer patients added  revealed over-POSSUM, compared with CR-POSSUM score which was more accurate, but the study was performed in patients undergoing colorectal surgery provost in general. It can be appreciated that the introduction of additional parameters of cardiac and pulmonary risk might improve the prognostic value for CR-POSSUM score. The association has verified the scores achieved, the aim is to increase the accuracy of forecasts. However, marking systems tend to optimize the data obtained in the study group. Although the CR-POSSUM score using data both to calculate and to validate the results, it is still important to check its validation and application in various populations. The results of this study demonstrated that both CR-POSSUM score and Mannheim have prognostic value for patients with abdominal sepsis in colonic peritonitis, both excluding scores surgery. Although both scores are based on clearly defined variables available, there are also differences. The association of several system scores in the case of CR-POSSUM and score Mannheim, do not only increase the prognostic accuracy of the evolution of patients with abdominal sepsis and provide a meaningful vision, for both the patient and the surgeon on surgical risk, while allowing a comparison of the types of surgery and medical care.


Despite being governed by the principles of nonequilibrium transitions, gene expression dynamics underlying cell fate decision is poorly understood. In particular, the effect of signaling speed on cellular decision making is still unclear. Here we show that the decision between alternative cell fates, in a structurally symmetric circuit, can be biased depending on the speed at which the system is forced to go through the decision point. The circuit consists of two mutually inhibiting and self-activating genes, forced by two external signals with identical stationary values but different transient times. Under these conditions, slow passage through the decision point leads to a consistently biased decision due to the transient signaling asymmetry, whereas fast passage reduces and eventually eliminates the switch imbalance. The effect is robust to noise and shows that dynamic bifurcations, well known in nonequilibrium physics, are important for the control of genetic circuits. This process is driven by gene and protein circuits, which are fundamental for the regulation of many cellular processes, including cell differentiation As mentioned above, we study a paradigmatic decision circuit consisting of two mutually repressive proteins under the action of two signals  and  , and equWith the intent of determining the number of attractors existing for a certain combination of input signals, we performed bifurcation analysis of the circuit using the software XPPAUT   the systThe situation changes qualitatively if we consider that the two external signals grow at different rates, which is a more realistic situation. In this case the cellular decision path is ient see , the memThe behavior described above is robust to noise. We now study the effect of the signaling speed on the decision. To that end, we vary the value of tant see . In thatte , see . The plo  ratios .For comparison purposes we also show in So far we have considered that the time scales of phosphorylation and production of transcription factors were equal. Yet, extracellular signals usually change the activity state of transcription factors in a sub-second scale, while transcription and translation of target genes may take minutes, and accumulation of protein products minutes to hours, with the additional delay being due to macromolecular transport alue see . For simThe mechanism of SdCDM can be understood from previous studies in dynamic bifurcations and parameter sweeping experiments in physical systems transient and non-additive. It is an open question which additional dynamics can appear due to the interplay between speed of asymmetry emergence and speed of decision making. It would also be interesting to understand, through analytical techniques, the importance of reaching the maximum asymmetry Certain cell differentiation processes are driven by slow build-up of decision-driving signals try  see  before oWe can conjecture that evolutionary adaptation has provided embryonic development with the optimal speed for cellular differentiation and, consequently, deviation from this speed may lead to pathologies. The conditions leading to such anomalies, and their potential treatment, constitute still an important open question. The mechanism demonstrated here should have further impact in investigations of genetic circuits with high dimension and undergoing more complex types of bifurcation The dynamics of the protein concentrations involved in our circuit see  is descrRespectively for the protein see also .Eqs. (1) to (4) were derived by assuming that transcription factor binding and unbinding, on the one hand, and In Eqs. (6) and (7) the functions Correspondingly for Correspondingly for protein All bifurcation diagrams see  were creand  see .Furthermore, all simulation results were performed by numerically integrating the stochastic differential equations using the Heun method ed , see . In ordesee  see , the setWith respect to


Thirty-seven trials were published in English [all randomized controlled trials (RCTs)] and the remaining articles were in Japanese only. The sample size for most studies was small (two-third of the studies included less than 100 patients) and the overall methodological quality appeared to be low. None of the studies used Kampo diagnosis as the basis for the treatment. In order to evaluate Kampo as a whole treatment system, certain aspects should be taken into account while designing studies. RCTs are the appropriate study design to test efficacy or effectiveness; however, within the trial the treatment could be individualized according to the Kampo diagnosis. Kampo is a complex and individualized treatment with a long tradition, and it would be appropriate for further research on Kampo medicine to take this into account.The Japanese traditional herbal medicine, Kampo, has gradually reemerged and 148 different formulations  can be prescribed within the national health insurance system. The objective of this article is to introduce Kampo and to present information from previous clinical studies that tested Kampo formulae. In addition, suggestions on the design of future research will be stated. The literature search was based on a summary, up until January 2009, by the Japanese Society of Oriental Medicine and included only those trials which were also available in either Pubmed or ICHUSHI . We included 135 studies, half of these studies ( Japanese traditional herbal medicine (Kampo medicine) obtained the unique features observed today during its phase of long historical development in Japan. In Japan, the administration of crude herbal drug formulations dates back by more than 1500 years. Recent decades have seen a revival of Kampo medicine in medical practice, accompanied by a scientific reevaluation and critical examination of its relevance in modern health care [Shang han lun. During the Edo-period from 1600 onwards, the specific Japanese characteristics of Kampo took shape. The seclusion of Japan from the outside world led to ever increasing differences from the predominantly Chinese concepts. The huge variety of the thousands of Chinese crude drugs was reduced to ∼300, those being the most efficacious drugs which were subsequently combined into ∼300 prescriptions. From a pragmatic point of view, Japanese physicians criticized the highly theoretical and speculative nature of Chinese medicine as being inadequate to meet the problems of every-day practice. The strongest critique came from Yoshimasu Todo in the 18th century who wrote: “In clinical medicine, we should only rely on what we actually have observed by examination of the patient”. For Yoshimasu Todo, one way to gain data on the condition of the body was to examine the abdomen, for which he developed a refined palpation technique (fukushin) [The term “Kampo”, which literally means “method from the Han period (206 BC to 220 AD) of ancient China”, refers to its origin from ancient China. The basic therapeutic handbook for the application of herbal prescriptions was the It is not surprising that many Japanese physicians were drawn towards medical techniques from the West to improve their therapeutic options in surgery, but most of them continued to use traditional Kampo prescriptions for treating problems of internal medicine until the 19th century. At the end of the 19th century, it became obvious that for the urgent medical problems of that time, infectious diseases and acute surgical problems, Western medicine had better tools. The German system of medical education was adopted. In 1876, the government passed a regulation that all physicians were required to study Western medicine. The practice of Kampo was not forbidden but greatly inhibited and gradually declined . HoweverAlthough rooted in Chinese tradition, Kampo medicine is not the same as modern traditional Chinese medicine (TCM). TCM emphasizes the traditional concepts of East Asian natural philosophy, such as Yin and Yang and the theory of the five elements. Japanese Kampo favors diagnostic methods that directly relate the symptoms to the therapy, bypassing speculative concepts. The vast array of crude drugs has been reduced in Kampo and also the quantity of each drug in the formulation is much lower. While Kampo still uses traditional prescriptions, TCM also tends to create new drug combinations .Kampo traditional prescriptions have been included in the Japanese National Health Insurance drug list since 1971. A total of 148 Kampo herbal prescriptions are able to be funded to date. The application of Kampo has steadily increased and according to a survey by the Journal Nikkei Medical, more than 70% of physicians prescribe Kampo drugs today .The development of modern ready-to-use forms was directly related to the enormous increase in Kampo usage, mainly as spray-dried granular extracts of the original formulae. They have increasingly replaced the traditional decoction of the crude drugs, even though they are also covered by the national insurance system. Besides being simple to administer, industrial production has enabled several other advantages. The quality control of the purity as well as toxicity is standardized in Japan, following the Japanese pharmacopoeia and internationally established regulations for Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP). The standardization of the main components has become possible and this is a precondition of clinical research. Today, extract preparations make up to 95% of the Japanese Kampo market.In Western countries, herbal therapies originating in other cultural areas, mainly Chinese herbal medicine as part of TCM, are receiving increasing interest. In the USA, TCM is still far more visible than Kampo. The practitioners practice herbal therapy often in combination with acupuncture, which is often a mixture of Chinese, Japanese and Korean acupuncture styles. Kampo drugs are only available over the counter, meeting Japanese GMP criteria. Since Japanese pharmaceutical companies have started clinical trials in the USA, several drugs have already been registered as investigational new drugs (IND) by the Food and Drug Administration. Safety and toxicity data from Japan are generally accepted by the US and European agencies.In Europe, especially in Germany, there is a long-term tradition of herbal medicine, and there is growing interest in Chinese phytotherapy and Japanese Kampo is also getting more and more attention. However, there is a shortage of doctors specialized in Japanese Kampo.ki , ketsu (blood) and sui (body fluid). The subjective complaints and the symptoms observed by the physician are combined to an individual symptom profile, a Kampo diagnosis (sho), which leads to the selection of the appropriate prescription [Kampo is an individualized treatment system where the overall condition of the patient and their constitution are of real importance; additionally, Kampo has a holistic therapeutic approach, as the mind and body are seen as one entity. The therapeutic aim is to relieve symptoms and to restore harmony in bodily functions. The treatment regime is based on symptoms. For the determination of the appropriate herbal prescription, the physician carries out a thorough investigation of the complaints and symptoms of the patient, including taking their temperature, examining sensation, weakness or sweating, symptoms which are not often primarily taken into account in conventional medicine. The physical examination includes abdominal palpation, tongue inspection and pulse diagnosis. This provides additional information concerning the state of the disease, by gathering the amount and distribution of cription . It may sho is close to the conventional diagnosis. However, in most cases, the traditional individual approach, where each patient receives their appropriate prescription, is the preferred option. For example, diseases that are expected to respond to the formula Kakkonto are diagnosed as Kakkonto-sho and it naturally follows that Kakkonto is prescribed in such cases.Japanese physicians with limited education in Kampo diagnostics tend to apply the formulations according to conventional Western diagnoses. This makes sense for some limited indications, if the formula for the Kampo sho) codes have already been published in Japanese [These special conditions have made clinical research in the field of Kampo medicine more complex than the research on conventional drugs. The World Health Organization West Pacific Regional Office (WHO/WPRO) has put considerable efforts into standardizing East Asian traditional medicine . WHO heaJapanese .Our search was based on an evidence report of Kampo treatment made by the Japanese Society of Oriental Medicine (JSOM) which included 320 clinical trials between 1986 and 2008. . This reKampo compared with either no treatment or different Kampo formula.Kampo compared with placebo.Kampo compared with standard treatment.n = 68) used a standard control, 28 used a placebo control, 24 had no treatment control and in 15, another Kampo formula was used as a control Among the 135 clinical studies, 106 were randomized controlled trials (RCTs), 6 quasi-RCTs and 10 were cross-over studies. There were 13 non-randomized comparative studies. Among the 106 RCTs, 23 studies were placebo-controlled. More than two thirds of the studies used only Kampo as verum, whereas in 38 studies, Kampo was used in addition to the standard treatment. Almost half of the studies , which was evaluated in nine studies. Many of the trials had low methodological quality  and thus a publication bias is to be expected. With respect to the methodology, it is interesting to note that in all studies summarized here, the treatment was based on the Western diagnosis only. A Kampo diagnosis was not mentioned in any of the trials. However, one trial seemed to be more individually based, using seven different Kampo formula in the verum group .The research available followed a Western approach and concentrated on single Western diagnoses treated with one Kampo formula. Since Kampo is a comprehensive and complex treatment system with a traditional approach, many research questions still need to be investigated. Kampo has been used for hundreds of years and is well integrated into the Japanese health care system, therefore it should be taken into account using an appropriate research strategy. When performing clinical research identical questions must be addressed for every new treatment, as well as for traditional treatments, which are already on the market:For whom and what is it used to treat?Is it safe?Is it superior to placebo?Is it superior or equivalent to conventional standard treatment?For traditional treatments, the order of research questions should differ from conventional drug research, because traditional treatments are already widely available . First, All of these questions could be answered using a prospective observational study which evaluates these aspects in usual care. This has been done for other traditional treatments such as homeopathy –153, andsho not only based on objective findings, but also from the subjective complaints. The evaluation of the Kampo treatment by the physician is sometimes decided based on the subjective symptoms. Current Kampo clinical research has not taken this aspect into account. Due to the individualized treatment approach of Kampo, subjective outcome measures are relevant and should always be considered while planning a study. In addition to databases, some authors have also suggested that more individual single-case research including N of one trials would be suitable to reflect Kampo medicine [Objective outcome measures which are often used in experimental RCTs are sometimes separated from subjective feelings. Kampo physicians value subjective complaints and diagnose medicine , 156. ThPrevious research has followed the principles of conventional drug research by testing the superiority of a single Kampo formula over a placebo for a clearly defined conventional diagnosis. An RCT from 1998, for example, compared Rikkunshito with a kind of placebo (low dose of the same formula) for the treatment of dyspepsia . ResultsNevertheless, this kind of research does not represent the traditional Kampo treatment. A traditional treatment is led from the Kampo diagnosis . If the aim of a clinical trial is to ask whether Kampo treatment in a traditional way is efficacious or not, the traditional treatment system has to be taken into account. For this purpose, an additional Kampo diagnosis with the conventional diagnosis could be used for choosing the appropriate Kampo medicine. There are two options; the first excludes the influences of the Kampo diagnostic procedure and the study could be performed in a similar way as suggested for the placebo-controlled study. When this design is used, the Kampo diagnosis is performed for all patients before randomization, although it is only needed for the group that actually receives Kampo.The first design is that Kampo diagnoses and an appropriate treatment could be used for stratification within the randomization process see . This deFor many Western diagnoses, more than two Kampo diagnoses are common. Different patterns would result in a larger number of subgroups and some of these might be too small to have enough statistical power for subgroup analysis. For this reason, it makes sense to use the pooled patterns for primary analysis and to pre-specify subgroup analysis for the more common patterns. Another possibility, which might be easier to handle for the trial process, is to use the Kampo diagnosis as additional inclusion criteria and to recruit only those patients with relevant Kampo diagnosis for the formula under research. An example for this can be seen in the study by Kobayashi . When usDoctors and patients want to know whether it is better to use Kampo instead of, or in addition to conventional treatment. Depending on its causality or external validity, the main focus of these studies could be performed more experimentally (homogenous patients and clearly defined treatment protocols) or more pragmatically  . EspeciaThe second possibility is to see the diagnostic procedure as part of the Kampo treatment, and the diagnostic procedure be used only on the Kampo group after randomization Patient preferences and patient expectation can play a role in complementary and alternative medicine trials. Two systematic reviews suggest that the influence of patient expectations on outcomes is related to both within-group changes and between-group differences , 162. ThKampo is a holistic and individualized treatment with a long tradition and future research is required to take this into account. RCT is the appropriate study design for testing efficacy or effectiveness, however within such a study, the treatment should be individualized according to the Kampo diagnosis.This work was supported by Grant-in-Aide for Research on Applied Use of Statistics and Information, Health and Labour Sciences Research and Clinical Research for Development of Preventive Medicine and New Therapeutics from Ministry of Health, Labour and Welfare of Japan. This work was also supported by the Center for Clinical Trials, Japan Medical Association. Claudia Witts' Chair for Complementary Medicine is endowed by the Carstens-Foundation. Research grant for doctoral candidates from the German Academic Exchange Service (DAAD) to L. H.


Many clinical studies have investigated the use of mental practice (MP) through motor imagery (MI) to enhance functional recovery of patients with diverse physical disabilities. Although beneficial effects have been generally reported for training motor functions in persons with chronic stroke , attempts to integrate MP within rehabilitation programs have been met with mitigated results. These findings have stirred further questioning about the value of MP in neurological rehabilitation. In fact, despite abundant systematic reviews, which customarily focused on the methodological merits of selected studies, several questions about factors underlying observed effects remain to be addressed. This review discusses these issues in an attempt to identify factors likely to hamper the integration of MP within rehabilitation programs. First, the rationale underlying the use of MP for training motor function is briefly reviewed. Second, three modes of MI delivery are proposed based on the analysis of the research protocols from 27 studies in persons with stroke and Parkinson's disease. Third, for each mode of MI delivery, a general description of MI training is provided. Fourth, the review discusses factors influencing MI training outcomes such as: the adherence to MI training, the amount of training and the interaction between physical and mental rehearsal; the use of relaxation, the selection of reliable, valid and sensitive outcome measures, the heterogeneity of the patient groups, the selection of patients and the mental rehearsal procedures. To conclude, the review proposes a framework for integrating MP in rehabilitation programs and suggests research targets for steering the implementation of MP in the early stages of the rehabilitation process. The challenge has now shifted towards the demonstration that MI training can enhance the effects of regular therapy in persons with subacute stroke during the period of spontaneous recovery. The ever-increasing number of publications attests to clinician expectations of mental practice (MP) through motor imagery (MI) as a means of promoting the recovery of motor function , that the simulation of movements evokes similar autonomic responses and that the imagination of an action or its physical execution engage largely similar neural networks  or with Parkinson's disease (n = 2) . It is also important to consider when MP is combined with PP, if it is within the same training session or a few hours apart in separate sessions. Thus, three modes of MI delivery have been proposed based on the analysis of the research protocols of 27 clinical studies in persons with stroke (2) Table . This cl2) Table . A firstAnother observation is that 74% of the studies 20/27) included patients more than 6 months post-stroke (chronic phase) after they had completed formal rehabilitation  or by audiovisual means  with a content unrelated to the tasks practiced. This control for contact-time is not always provided , the ratio of MP to PP for training varied: 5MP: 1PP  since these are rarely counted. There is not only much variability in both the amount of time dedicated to MI training and in the mode of MI delivery, but one must also ponder whether the mental rehearsal was done correctly. Very few studies assessed the MI ability of participants Tables , 4, so tAlthough standardized audiotape delivery makes such manipulation checks more difficult, it can be done. Nilsen et al.  conducteA frequent question about MP in neurological rehabilitation is how much practice  is necessary to promote learning effects? In this section, we try to relate MI training parameters to findings from studies using similar outcomes measures so as to derive indicators for success. In the majority of the studies with a separate mode of MI delivery for training ADL tasks, the same tasks were practiced both physically and mentally and the mental rehearsal part was delivered through audiotaped scripts (mode 1A) preceded by relaxation exercises  of mental repetitions  in studies with audiotaped scripts Page, . What arIn usual practice, listening to relaxation exercises on a pre-recorded audio media has been considered as a neutral procedure and used in studies post-stroke as a sham intervention to control for contact time  during mobility tasks such as rising-up from a chair and sitting-down, the best marker of improvement is a gain in the amount of limb loading  on the affected side , Fugl-Meyer Assessment (FMA) or Motricity Index (MI). Although these clinical scales are very reliable Lyle, , and proWhen examining Figure Few clinical studies have examined the specificity of MP training, by focusing on a single ADL task. The use of quantitative outcome measures such as a computerized test for assessing reaching times, the Box and Block test and the Purdue pegboard test might help gain a better understanding of the specific effects of MI on function. Crajé et al.  showed tIt is also important to assess generalization effects of MI on function. In a pilot study  are useful because they extend our understanding of the mechanisms contributing to the positive effects of MI training.SD of 1.1 and 1.4, respectively) indicating that the 5 patients in each group had initially a similar level of activity limitation, and, as reflected by the SD of the mean change scores, they all improved in a similar manner indicating that all were good responders. In contrast, in the studies with larger patient groups at an earlier stage of recovery  who had suffered a recent stroke and lived in a nursing home , as well as the images and sensations during the completion of the task. Also, the wording can be very motivating, as it encourages patients to see the arm and hand moving freely and easily, and that the task is being performed effectively  on how the movement should be performed are given. This is a very dynamic approach and requires a close interaction between the patient and the therapist who guides the patient throughout the stages of motor learning during both mental and/or physical rehearsals , a wide spectrum of tasks, cognitive limitations, compliance with MI training, and relatively inexperienced therapists in the use of MP. Therefore, a first action would be to control factors that can be controlled such as: screening for impeding cognitive problems, assessing MI ability, determining an optimal number of tasks, training the therapists, planning for manipulation checks of MI and identifying valid primary and secondary outcome measures, while taking into account the advantages of each mode of MI administration along the rehabilitation continuum. The following strategy proposes a 3-step framework for the integration of MI intervention in current clinical practice Figure .Adding mental exercises to a training session that can sometimes be considered already too short can be viewed as too daring, especially if the patient is still a little confused and fatigues rapidly. So, at this stage, MI training should not be too demanding, both in terms of time and mental effort to learn the procedures. Therefore, to avoid removing time dedicated to regular therapy sessions, one might consider adding MI in a separate mode of administration with audio scripts , audiovisual support, or web or stand-alone computer applications. This mode requires less professional resources once the scripts and the material are developed. At this stage, the aims would be to introduce MI, to familiarize the patient with MI, and to apply MI training to one or two tasks with scripts to learn the movement strategy and gain confidence for successful performance. The role of this MI training would be to prepare for the next rehabilitation training session when the same task is practiced physically to promote learning. This part of MI training would be the equivalent of performance preparation described in athletes prior to competition, and likewise the focus of training should be put on factors that enhance performance such as strategy, motivation and concentration Paivio, .Once the patient is well-familiarized with MI, the next step could then be to gradually introduce mental rehearsals of tasks that are also trained physically in regular training sessions (starting with a simple task and then increasing the number and complexity). This part relates to skill learning and the idea is to increase the number of repetitions through MI. It requires a close interaction with the therapist giving instructions adapted to individual needs and limitations . With the concurrent mode of MI intervention, feedback about physical performance is given by the therapist who also makes regular imagery checks to control for compliance and quality of MI. Because this approach is more demanding at the beginning, it is advised to start with a small number of mental repetitions and the ratio between mental and physical repetitions should be gauged according to individual capacities. This procedure has been integrated successfully into regular practice , relaxation, instructions and valid outcome measures . Motor learning theories in relation with the modes of MI delivery should also be examined. Because of the functional similarities between MI and motor execution, one would think that they share similar rules relative to motor learning, but recent findings in healthy adults have shown that while task variability promotes skill learning with physical practice, it does not have the same effect with mental practice  of motor recovery to guide their use. Thus, it is important to systematically record the content and quantity of training regimens  to gain some understanding of the dose-related responses associated with each mode of MI delivery. Also, it is essential to select patients that can engage in MI and to use manipulation checks to confirm their adherence to MI training. The selection of valid outcome measures specific to the trained tasks is a central issue; the choice of outcomes should be based on psychometric properties such as reliability and sensitivity to ensure detection of clinically significant changes. Finally, sub-group analyses are required to characterize responders from non-responders to a given MI training. This review proposes a framework to assist in the integration of MI into rehabilitation programs. We know little about the potential use of MP in persons with subacute stroke. Thus, the challenge has now shifted towards the demonstration that MI training can enhance the effects of regular therapy in persons with subacute stroke during the period of spontaneous recovery. The proposed framework is only a starting point. The combined effort of clinicians and researchers is essential to put it to the test, and to adjust it in accordance with ongoing clinical findings.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.