The aging phenomenon results in body organ system debilitating, which causes the balance weakening and makes a fall, fracture rate, and further medical cost to increase. The lack of exercise has been linked to increasing the incidence of hypertension, coronary artery disease, osteoporosis, degenerative arthritis, and diabetes. Chronic disease affects patients both in psychological and physiological functions which limit their daily activity. In the past, many researches pointed out that these patients can improve their balance sensation by exercise. Because of the above reasons, this research implementation forms a wireless platform of information connection system and medical data analysis. First of all, the target population in the society focuses on those elderly with the common chronic diseases, such as skeletal muscle diseases and degenerative arthritis. Using the hydraulic resist practicing equipment as the mainstay intervention can help examinee collecting the practice value and further analysis. The platform of information accords not only the data prior and after the exercise but also graphic data presentation and analysis from the medical staff members providing services in the society. It can also provide the medical unit to create data mold and a body health counselor when services in the society. According to the definition from WHO, it is called an aging society when the population with age greater than 65 is above 7% in the proportion. The data of population statistics in Department of Household Registration indicates the aging society of Taiwan formed in 1993. The aging rate of Taiwan is only slower than the one of Japan in Asia. How to decrease the need of long-term hospitalization and the cost in society has become an urgent issue. If the age is above 75 years' old, it is even no half of it comparing with youths , 3.β-cell destruction, usually leading to absolute insulin deficiency), Type 2 diabetes (resulting from a progressive insulin secretory defect on the background of insulin resistance), and other specific types of diabetes and gestational diabetes mellitus. Hyperglycemia would increase the incidence of peripheral vascular diseases, sensitive nerve diseases, myocardial infarction, stroke, major arteries diseases, and other disease, which significantly increase the mortality rate of seniors.The lack of exercise has been linked to increase in the incidence of hypertension, coronary artery disease, osteoporosis, degenerative arthritis, and diabetes. Chronic disease affects patients both in psychological and physiological functions which limit their daily activity. Aging could depress whole body functions, which also increases the risks of many chronic diseases in senior population. The study of “Senior Mental and Physical Lives in Long Term Survey” from Bureau of Health Promotion, Department of Health, Taiwan suggests that there is at least one chronic disease for 88.7% of people above 65 years and 90.9% of people above 75 years old, having three chronic diseases in 56.4%. Of those chronic diseases, the most common five are hypertension, heart or cardiovascular diseases, diabetes, osteoporosis, and arthritis. Diabetes mellitus is a chronic disorder of carbohydrate metabolism, which includes Type 1 diabetes (2 and 0.007 g/cm2 each). The following references recommend that the resistance strength and training period still need randomized tests to verify them [In 2009, Davison with his colleagues collect the data from those of 60–80 years' old and have an enlarged abdomen .  Figureify them –17.According to The purpose of this research is to develop an automatic platform, which further extends to the platform used to collect and analyze medical data. The developing step of this system consists of three frameworks: (1) a highly stable and convenient wireless data collecting system, (2) a mutual interaction by the function of smart phone, and (3) a remote end platform of health data managing center. The health manager website could send and share the data to this center; thus, the examinee could survey their own health information.This research uses hydraulic resistant training tool, as the major intervention equipment, and recruits 45–85 years of age, both middle-aged and elderly involved, for participation. By focusing the hydraulic rod on the training equipment, this research edits an installable counting device for every hydraulic exercise device. By maintaining the original shape of exercise equipment as the prerequisite, that hangs the counting devise on the hydraulic rod of exercise equipment improves the repeating use rate and is substitutable. In order to further improve its convenience, this research equips an additional sensor of sliding on the system for counting the number of times the user uses the equipment as shown in The control device is set up for signal receiving, timing, wirelessly data transporting, and numbers presenting. When user operates first pull on the hydraulic rod of the system, the sensor of sliding would signal to the control device. Based on the time set, it counts back when the training equipment is used and alarms out and sums up a total at final. Through the Bluetooth transportation, it transfers this data to the monitor and presents the number of operating on the monitor. Monitor mainly consists of Bluetooth communication function, which thus improves systemic integrity, greatly minimizes the quantity of devices, directly receives exercise records from control devices, and finally uploads data to the cloud inventory.As inCombining interactive dictation function within application function list of smart phone and then adopting multitouch panel and intrinsic Bluetooth and phonetic functions, and so forth, the dictations are achieved by audio alarm and suggestion, which enables users not only to avoid sport injury but also to simulate actual personnel dictation, to record training history, and to save in intrinsic memory of the smart phone. Finally, it appears as shown in This research develops a versatile and interactive web interface. Based on the medical doctor's suggestion and cooperation in one-month period data collection, this system adopts models website framework with service-oriented architecture and web operating system. Concerning the operating convenience and the website accommodation, the website, through the wireless pathway, would transfer the physiologic data to this system, which not only decreases systemic repetition but also provides versatile interfaces for different authorities.(1) The individual health management function provides the user with the independent health management service. Once the user completes the health checkup, the healthcare personnel will input the checkup data into the cloud database via the Internet. The web interface allows the users and their families to query the users' health checkup results and related data via mobile devices or the PCs at any time without installing any other tool .(2) The system distributes the online users to the specific level based on the privilege of the account; thus, the users will be distributed to the user level and linked with the database of the checkup data for data access and analysis. The expert system will display the analyzed checkup data together with the brief interpretation for the results on the webpage. For example, systolic pressure is higher than 120; diastolic pressure is higher than 80; heartbeat is higher than 100/min or lower than 60/min . The sys(3) The healthcare personnel input the physical checkup records into the database via the web browser and the inputting application provided by WebOS. After that, the expert system will process the data and save them to the right location of the database. As for the service of medical information analysis platform, it allows the users, their families, and the medical care institutions to obtain the status of the users' health checkup through the devices, such as PC or smart device, which also provides the analysis reports and brief interpretation of the checkup results. The operation interface of the platform adopts the modular web architecture. Besides reducing the repeated system design, it could also provide different functional interfaces based on different privileges. Below is the introduction of the functions provided by the health management service platform built in the system.This system hangs counting device on a hydraulic rod in order to improve the utilization, update, and replacement rate. The physical data analysis function stores and analyzes the physical checkup data in the database as shown in Based on the research, hydraulic resistant exercise can be recommended for those with osteoporosis for improving bone density. It also responses to the government advocating whole citizen sport. In addition, using the hydraulic resist practicing equipment as the mainstay intervention can help examinee collecting the practice value and further analysis. The platform of information not only accords these values into the data prior and after the exercise, but also helps providing graphic data presentation and analysis from the medical staff members providing services in the society. It can also provide the medical unit to create data mold and a body health counselor when services in the society.


How to assess the impact of research is of growing interest to funders, policy makers and researchers mainly to understand the value of investments and to increase accountability. Broadly speaking the term "research impact" refers to the contribution of research activities to achieve desired societal outcomes. The aim of this overview is to identify the most common approaches to research impact assessment, categories of impact and their respective indicators.We systematically searched the relevant literature ) and funding agency websites. We included systematic reviews, theoretical and methodological papers, and empirical case-studies on how to evaluate research impact. We qualitatively summarised the included reports, as well the conceptual frameworks.We identified twenty-two reports belonging to four systematic reviews and 14 primary studies. These publications reported several theoretical frameworks and methodological approaches . The "payback model" emerged as the most frequently used. Five broad categories of impact were identified: a) advancing knowledge, b) capacity building, c) informing decision-making, d) health benefits, e) broad socio-economic benefits. For each proposed category of impact we summarized a set of indicators whose pros and cons are presented and briefly discussed.This overview is a comprehensive, yet descriptive, contribution to summarize the conceptual framework and taxonomy of an heterogeneous and evolving area of research. A shared and comprehensive conceptual framework does not seem to be available yet and its single components  are often valued differently in different models. It is widely accepted that research is a crucial investment to foster innovation, knowledge advancement, and social and economic development. For example a knowledge gain is assumed to result from biomedical and basic research; if such an output is then properly translated in a short but reasonable time lag, it will lead to a better health status for populations and patients. Much of the information produced is not easily transferable to patient care and this has led to the concept of the so called "translational blocks" . EvidencBy definition, research activities are risky and their returns highly unpredictable. So, any attempt to increase the research system's effectiveness, and to assure and monitor quality, is welcome by the whole scientific community and funders . CompetiThe objective of this overview is to describe the conceptual and methodological approaches to evaluate the impact of biomedical and health research. Specifically, we aimed at collecting and qualitatively summarizing what is available in the biomedical literature in terms of theoretical framework and methodologies, with a specific focus on the most valid and reliable indicators of impact. Our objective was also to see whether this qualitative analysis would have allowed the identification of a preferred model to measure research impact and to identify the desirable elements  that a reference model should have.Other key elements in the "research governance debate" such as the analysis of different modes and approaches to research funding, prioritization of topics, or the analysis of barriers and facilitators to the translation of research results were beyond the scope of this overview.In the context of this overview, the term "research impact" refers to any type of output of research activities which can be considered a "positive return" for the scientific community, health systems, patients, and the society in general. We refer to any type of health-related research, basic and biomedical, such as new drug or technology development - and applied research such as clinical trials, health service research, and health technology assessment (HTA).The complexity and heterogeneity of the topic made the conceptualization of this overview much less straightforward than typical review on medical interventions. We therefore followed the methodology recommended by the Cochrane Collaboration for preparing "overviews of review" rather than following the steps involved in critically appraising the primary studies for a systematic review (SR) . We firsGiven the broad perspective of the review, the methodology to identify relevant studies comprised an iterative process. We first performed a systematic search on bibliographic databases (Medline and The Cochrane Library) using a modified version of the search strategy proposed by Martin Buxton and collaborators . The seaFinally, we screened the citations reported in the included publications and assessed the literature in the field already retrieved by authors. We did not contact study or report authors.Two reviewers independently selected relevant publications by screening titles and abstracts. After the retrieval of the selected full text publications and, if needed, of associated publications, we extracted the following details: objective, country and setting, evaluation time lag, conceptual model methodology, main results and conclusions.From the analysis of the literature and with reference to the more widely accepted theoretical models we attempted a description of the categories of impact more frequently measured, focusing on the indicators and metrics for each category.Given the heterogeneity of study designs, the different objectives and the lack of a standard methodology between studies, we did not perform a quality assessment of the methods used in different studies.From the bibliographic databases and web searches we identified 1064 records. Among these 38 potentially relevant publications were retrieved as full text  that invest more in research. Research in this area focuses on three broad areas: i) theoretical frameworks and models aiming at assessing research impact with respect to multidimensional and integrated categories; ii) methodological approaches to the evaluation exercise; and iii) development of valid and reliable indicators and metrics.A common and key feature of most of the used models is the multidimensional conceptualization and categorization of research impact. Different impact aspects are connected and integrated using a variety of theoretical approaches (i.e. Logic model for the Payback framework). Assessment of research impact that consider more than one category are indeed valued for their ability to capture multifaceted processes.ad hoc case studies. The latter seems a reliable methodology: case study implies an explicit and a priori choice to start and conduct an evaluation exercise with specific aims and features. However, they can be at risk of "conceptualization bias" and "reporting bias" especially when they are designed or carried out retrospectively. Finally, feasibility and costs of case studies are also a major barrier to their conduct and subsequent use. In general, the methodology should be as flexible and adaptable as possible to many assessment questions, viewpoints, settings, and type of research and should guarantee the quality of collected data.Several empirical approaches have been used to practically assess research impact: desk analysis, including bibliometrics, peer reviews, interviews, The lack of standard terminology, the multifaceted nature of the evaluation, and the heterogeneity of the empirical experiences make it hard to identify a preferred model. The most cited impact dimensions are related to knowledge, public health and socio-economic advancements. The Payback model, -41 and iThis overview highlights the methodological limitations of the studies carried out in this field, which are briefly summarized below.First, the vast majority of the studies were retrospective, based on interviews to principal investigators or funders, and mainly focused to record the projects' achievements rather that their pitfalls and limitations. This could lead to several biases, such as selective recall or reporting of (positive) results. The second major limitation is linked to the "attribution", the possibility to postulate a causal link between observed (or expected to be observed) changes and a specific research activity . AnotherThe main limitations of this overview concern the study retrieval process and the definition of the eligibility criteria. We experienced several difficulties in planning the search strategy, all caused by the heterogeneity of definition and the lack of a standard terminology to describe "research impact". Bearing this in mind, we adopted an approach capable of maximizing sensitivity rather than specificity, that is the application of broad inclusion criteria and the use of several sources of information, not only bibliographic databases. As expected, only 30% of the included publications were found through the traditional biomedical databases (i.e. Medline). Beyond a high variability in the way of indexing these articles, this could be due to a limited interest in the publication of these evaluations, which were considered, at least in the last decade, an administrative duty rather than a scientific activity. Thus many relevant studies were retrieved in the "grey literature" (i.e. funding agency's reports) and not in scientific journals. Even if we were not able to apply a systematic approach to website consultation, we believe this effort had increased the comprehensiveness of our search.Another methodological limitation of this overview is that we did not estimate the level of publication bias and selective publication in this field. Finally, as our analysis include study up to 2009, we did not capture new important emerging approaches to impact assessment, such as the Research Excellence Framework (formerly RAE) .The main message of this overview is that the evaluation of the research impact is as yet a heterogeneous, and evolving discipline. Multidimensional conceptual frameworks appear to be adequate as they take into account several aspects of impact and use advanced and analytical approaches  to their evaluation. It remains to be clarified how different impact dimensions should be valued and balanced by assessors to fit them to their specific purposes and contexts. Added values to the multidimensional approach are to pursue an explicit planning of the assessment exercise and to carried out the alongside the development of research programs, through monitoring and prospective data collection.This overview should be seen as a preliminary step toward a shared conceptual framework and taxonomy to assess research impact rather than an indication of an ultimate model, that probably appears unrealistic.The authors declare that they have no competing interests.All authors were involved in the conception of the study. RB, LM, VP, and AL were responsible for the study design and acquisition, analysis, and interpretation of data. VP was responsible for the search strategy design and the study retrieval. All authors contributed to the preparation of the final text of the article, they critically revised it for important intellectual content and gave final approval to the manuscript.This overview was developed within the project "Research impact in Emilia Romagna: an open archive of health research outputs. Evaluation of research products and capacity building" funded by the Programma di Ricerca Regione Università 2007-2009, Regione Emilia Romagna, Italy.The funder had no role in study design, collection, analysis, interpretation of data, writing of the manuscript, and in the decision to submit the manuscript for publication.http://www.politichesanitarie.it, Banzi, R. Pistotti, V., Moja, L., Facchini A., Liberati A. Valutazione dell'impatto della ricerca biomedica e sanitaria: revisione sistematica di letteratura Politiche Sanitarie 2010, 11(3): 175-195).We acknowledge that this paper is a revised version of a first overview published in Italian in the journal "Politiche Sanitarie" (Appendix 1. Search strategy used for Medline (up to May 2009) and website searched to retrieve relevant report not published in the scientific journalsClick here for fileTable s1. Qualitative description of the included SRsClick here for fileTable s2. Qualitative description of primary studies not included in the previous mentioned reviewsClick here for file


Prescription of antimalarial drugs in the absence of malarial disease is a common practice in countries where malaria is endemic. However, unwarranted use of such drugs can cause side effects in some people and is a financial drain on local economies. In this study, we surveyed the prevalence of malaria parasites in humans, and the prevalence of the malaria transmitting mosquito vectors in the study area. We also investigated the use of antimalarial drugs in the local people. We focused on randomly selected rural areas of eastern Pakistan where no malaria cases had been reported since May 2004.Mass blood surveys, active case detection, passive case detection, and vector density surveys were carried out in selected areas of Sargodha district from September 2008 to August 2009. Data pertaining to the quantities and types of antimalarial drugs used in these areas were collected from health centers, pharmacies, and the district CDC program of the Health Department of the Government of the Punjab.Culex mosquitoes was high. Substantial consumption of a variety of antimalarial tablets, syrups, capsules and injections costing around 1000 US$, was documented for the region.Seven hundred and forty four blood samples were examined, resulting in a Blood Examination Rate (BER) of 3.18; microscopic analysis of blood smears showed that none of the samples were positive for malaria parasites. Investigation of the mosquito vector density in 43 living rooms (bedrooms or rooms used for sleeping), 23 stores, and 32 animal sheds, revealed no vectors capable of transmitting malaria in these locations. In contrast, the density of Use of antimalarial drugs in the absence of malarial infection or the vectors that transmit the disease was common in the study area. Continuous use of such drugs, not only in Pakistan, but in other parts of the world, may lead to drug-induced side effects amongst users. Better training of health care professionals is needed to ensure accurate diagnoses of malaria and appropriate prescription of antimalarial drugs delivered to communities. Anopheles culicifacies and An. stephensi). Two new species, namely, An. fluviatilis and An. annularis are suspected of transmitting malaria in Baluchistan province [Malaria is a major vector borne disease that is the second most prevalent disease in Pakistan. Its transmission is seasonal, with epidemic outbreaks in Baluchistan, Khyber Pakhtoon Khawa (KPK) and Sindh province. It is predominantly a problem in the Federally Administrated Tribal Areas (FATA) and along the border of Iran and Afghanistan. However, in Punjab, the most populous province, it is less common and the disease incidence is much lower than in other areas of Pakistan. The disease is transmitted by the bite of an infected female mosquito belonging to the genus Anopheles. A total of 577 species of Anopheles mosquitoes have been recorded in the world, of which 77 species act as vectors for malaria. In Pakistan, about 24 Anopheles species are known; of these only two are malaria vectors  fatigue, anorexia, dizziness, pulmonary toxicity (Mefloquine), neuropsychiatric effects (Mefloquine and Chloroquine), effects on the retina, blindness, (quinine), and neurotoxicity targeting mainly the auditory and vestibular pathway (artemisinin in combination with Mefloquine) -12. InapThe objective of the present work was to study the prevalence of malaria, the vectors that transmit it, and the use of antimalarial drugs in randomly selected rural areas of the Sargodha district in the eastern part of the country that has seen no malaria cases since May 2004 .The selected area for the study was the union council (UC) # 125 in the Sargodha district of Pakistan. This UC is a thickly populated rural area comprising six villages with a total population of 23,359. This area is a vast agricultural landscape with an organized irrigation system consisting of channels, canals and tributaries. This UC is a central point for the surrounding areas and therefore has a good number of health facilities, consisting of one public sector Rural Health Centre (RHC), two private hospitals, 4 clinics with physicians and 20 quacks. A quack is an unqualified person that works in a rural area and has experience of working with a physician, after which he starts to prescribe or sell medicines to people. He has no diagnostic skills, nor access to diagnostic facilities. Quacks often work in areas where people have no qualified health care personal available to them or are too poor to pay a qualified physician. All the health facilities mentioned above do not have microscopes or rapid diagnostic tests for malaria diagnosis except RHC, where facility of microscopy was available but cannot be used because of a lack of trained staff.This area was randomly selected for study from areas where no cases have been reported for more than four years according to the monthly surveillance data from the CDC Program, Health Department Government of the Punjab. The present study is a small-scale preliminary study conducted in a small geographical area that has not been investigated previously.Three methods of blood sampling were used to collect blood samples for detection of human malaria parasites:i. Mass Blood Survey (MBS).ii. Passive Case Detection (PCD) at health facilities.iii. Active Case Detection (ACD) through house-to-house visits.Plasmodium spp. Slides were screened using a 100× objective, and 100 fields examined for the presence of malaria parasites The method used to screen the slides  is shown in Figure Blood samples were collected from September 2008 to August 2009. For MBS, 9 Government and 12 private schools were selected from the six villages within the UC. The blood samples were collected from all of the children and students who had a fever or history of fever attacks with symptoms of chills, headache and other malaria symptoms during the previous month. ACD was carried out by house-to-house visits to collect blood samples from suspected malaria cases. All houses were visited in the area for this purpose. Health facilities were visited regularly (average twice a week) during the study period for PCD. We obtained the assistance of health care professionals, health facility and clinic owners, and quacks, which was needed for blood sample collection from patients who attended the facility to seek treatment for fevers with chills and headache (pyrexia of unknown origin). The sample size was calculated at a 95% confidence level with a 5% confidence interval at the worst disease incidence of 0 to 3.535. Through use of the above sampling methods, we were able to keep the study area under continuous surveillance during the entire study period. This ensured that blood smears were collected from all of the suspected cases of malaria, alongside those cases that were diagnosed and treated by the physicians, health care providers, and quacks. The blood films were prepared and examined using standard World Health Organization (WHO) protocols for detection of To study the vector density in the selected area, adult mosquito collections were carried out in the morning, twice a month in all of the six villages. Mosquitoes were collected from bedrooms that had been slept in the previous night (insecticide treated bed nets were not used in these rooms or houses), animal sheds, and stores following standard WHO protocols and guidelines . A pyretData about the types and doses of anti-malarial drugs used for the treatment of malaria in the area were collected. To achieve this, a data analysis tool was designed. Twelve pharmacies were included in the study. The owners of these pharmacies were interviewed to obtain data about the quantity of antimalarial drugs used in that area as they were the main source of antimalarial drugs for the population. Data about the antimalarial drugs that were sold at each pharmacy or dispensed by practitioners during the study period were also collected. At the start of the study, the pharmacy owners were requested to provide information regarding the sales volumes of the different types of antimalarial drugs . Pharmacy owners were requested to provide regular updates on a monthly basis during the study period. The same data were collected from health facilities and the public sector, i.e., from the RHC and district CDC program, both of which were purchasing antimalarial drugs from the government medical store depot. The ethics committee department of the Biological Sciences University of Sargodha duly approved the study and its design.A total of 744 blood samples were collected ; from this, the blood examination rate (BER) of the total study population was calculated 3.18. The microscopy results showed no malaria parasites in the population; therefore, the malaria Parasite Incidence (PI) during the 12 months study period was zero , stores 23), and animal sheds (32) were screened for the presence of 3, and anTable Malaria in Pakistan has low to high endemicity. Areas with high endemicity include FATA, Baluchistan and KPK, whilst malaria endemicity in the Punjab is relatively low . The majAs malaria can be fatal, the general use of antimalarial drugs in malaria endemic countries is common. Before the Roll Back Malaria (RBM) program was implemented, the presumptive treatment of PUO cases remained a component of national policy implemented throughout country, including the Punjab. However, with the launch of the RBM program in 2003, the emphasis changed to one of its component “Early diagnosis and Prompt treatment” of malaria as part of the national health policy. According to National Treatment Guidelines, antimalarials should be given or prescribed after diagnosis, and presumptive treatment should be avoided as it may lead to parasite resistance and possible treatment side effects. However, whether effective communication of this policy to health providers and pharmacies has been successful is an open question. Hence, malaria is still overdiagnosed and excessive use of antimalarial drugs continues in the areas where there is no access to laboratory facilities to obtain an accurate diagnosis of malaria .General and specific blood surveys along with vector density studies are the key tools for better surveillance of malaria. Use of such approaches, would direct malaria control strategies  to the areas that need them. Such data would help health authorities to prioritize and allocate scare resources appropriately so that better health facilities are available in areas that need them. This is particularly important in third world countries where resources are scarce.In this study, we chose an area of Pakistan, in the Sargodha district, to evaluate the use of antimalarials in relation to the prevalence of malaria. Use of insecticide treated bed nets is not practiced in the area, being an area with no malaria case history since 2004. Similarly, no insecticide spraying has been carried out in the area since that time. However, people do use various kinds of mosquito repellents to avoid being bitten by mosquitoes.Plasmodium spp were not observed in any of the blood films from the sampled population. However, microscopy does have limitations for detection of parasites in areas with very low parasite prevalence. The BER was 3.18 for this area, a value that is higher than the value recommended for surveillance purposes [During the present study, An. culicifacies or An. stephensi mosquitoes were found in any of the areas sampled in the six villages. However, relatively large numbers of Culex mosquitoes were found. Among the Culex species collected, the ratio of male to female mosquitoes was very high. Culex densities were very high in animal sheds compared to stores and living rooms, which may reflect the feeding preference of these mosquitoes. In contrast, absence of Anopheline mosquitoes at the sampling sites might suggest that ecological factors, such as habitat competition  might exist. The use of pyrethrum spray for catching mosquitoes is a good method for collecting endophilic mosquitoes at rest indoors and provides good estimates of the mean mosquito density per house in a given area. However, it will miss mosquitoes that leave houses immediately after feeding, or include those that enter after feeding outdoor on another host. Anopheline mosquitoes in this area are not known to be resistant to pyrethroid insecticides; therefore, the absence of malaria vectors in the area during the study period provides important evidence to support the lack of parasites observed on blood films during the study period (PI =0).Consistent with the above findings, no Our data revealed that a considerable quantity and range of antimalarial were used to treat misdiagnosed malaria. Tablets constituted the largest number of antimalarials sold or used , whilst syrups (1155), capsules (422), and injections (170) were sold or used less frequently. The total amount spent by the local population on antimalarials was 79, 311/-PKR (approximately 1000$). This amount is almost equal to the total annual medical budget of a single basic health unit, which is a primary health care facility in this country.In the absence of malaria in the study area, the use of such large quantities of antimalarial drugs is irrational and particularly unjustified when there are no vectors that can transmit the disease. Not only was there no need for such medicines, they are expensive and may cause side effects in some people. The present study reflects the need for training to improve malaria diagnosis among health care professionals, as well as increasing awareness in the population. In particular, prescribing antimalarials injections without a confirmed laboratory diagnosis must be discouraged. Injections are very effective when they are prescribed properly, but may cause harm when used inappropriately .We conclude that, even taking into account the limitations of this small study, the high use of antimalarial drugs reported by the participating health facilities and pharmacies contrasts sharply with the lack of malarial disease and vector in the area during the study period. This type of practice needs to be redressed as it is causing economic loses and may lead to toxicity issues. There is a strong need to assess the malaria situation in such areas with the help of laboratory diagnosis as well as the vector presence at a large scale, not only to this part of the world, but in other places as well. Hence there is a need for increased training of health care professionals. Whilst looking for new malaria treatments and control strategies, it is also important to ensure that resources are not used to treat misdiagnosed malaria. Public awareness campaigns may help to educate people about malaria; however, surveillance remains an important tool in areas where malaria could still pose a threat to public health.The authors declare that they have no competing interests. Moreover they do not have affiliation and financial interest with any company/organization whose product appears prominently in the manuscript. There was no source of funding for this study.All the authors have equal contribution to this study, have read, and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/941/prepub


Pharmaceutical drug promotion is a means of informing health professionals about new drugs. The approach is often times unethical and inappropriate and may promote irrational prescribing. Dearth of information on impact of pharmaceutical drug promotion on prescribing behaviour of doctors in developing African countries has necessitated this study. We therefore aimed to determine the sources of drug information for doctors working in a teaching hospital in Nigeria and to assess the self-reported impact of the sources on their prescribing behaviour.A total of 163 doctors working at the University College Hospital (UCH), Ibadan in Nigeria were evaluated with a questionnaire for their demographics and sources of drug information. For doctors who relied on drug promotion, they were asked to self-report and self-rate their opinion on extent of interactions with pharmaceutical companies as well as how such interactions had impacted on their prescribing behaviour. Apart from the demographics, each question was evaluated with a typical five-level Likert item. Data analyses were with simple descriptive statistics.Of the 400 doctors working at UCH, only 40.8% participated in the study. Drug information was sourced from colleagues , reference books , pharmaceutical sales representatives-PSRs , promotion materials , scientific papers/journals/internet , and drug promotion forum/product launches . Each source was highly utilized but there was no wide variation in their pattern of use. According to the self-report of over a half of the respondents, PSRs was an accurate and reliable drug information resource; PSRs increased their awareness of the promoted drugs; and their prescribing behaviours were influenced by information from PSRs.Respondents tend to rely on a broad range of drug information resources which include potentially inappropriate resources such as PSRs. Since this study was based on self-report, the influence of drug information resources reported by the respondents on their prescribing behaviour may have been underestimated. Measures should be taken to minimize interactions between PSRs and the respondents. Irrational prescription is a public health problem with the potential to harm both the individual and society. It is, possibly a contributory factor to the increasing pharmaceutical expenditure world-wide. Drug expenditure is a major concern for policy makers in Europe and has prompted them to suggest healthcare reforms .Several factors have been identified to influence doctors’ prescribing decisions and practice –4. Some Disease mongering is a potential means of creating an enormous market for drugs  but its Drugs play an important role in the treatment of ill patients. In Nigeria, drugs are prescribed to more than 60 percent of the patients that consult with doctors , 13. PSRThe World Health Organization (WHO) defines pharmaceutical promotion as “all information and persuasive activities by manufacturers and distributors, the effect of which is to induce the prescription, supply, purchase and/ or use of medicinal drugs” . The WHOGiven the above problems and knowing that pharmaceutical companies play active roles in marketing their products, it is important to investigate how much influence these companies have on the prescribing behaviours of healthcare practitioners in developing African countries. Unfortunately, there is limited information on research in this area in Nigeria. This study is therefore aimed at determining the sources of drug information for doctors working in a teaching hospital in Nigeria and to assess the self-reported impact of the sources on their prescribing behaviour.This was a prospective study involving doctors working at the University College Hospital (UCH), Ibadan, Oyo State in Nigeria. UCH is a premier teaching hospital in South-western Nigeria. Approximately four hundred doctors are in the employment of this hospital. They are distributed into thirteen departments namely: internal medicine, surgery, paediatrics, family medicine, obstetrics and gynaecology, ophthalmology, otorhinolaryngology, radiology, radiotherapy, dentistry, community health, accident and emergency, orthopedics and trauma. Due to the small number of doctors in some departments and for the convenience of sample analysis, internal medicine and accident and emergency departments were grouped together as general medicine. Similarly, surgery, ortorhinolaryngology, and orthopedics and trauma departments were grouped together as surgery specialties. Only seven of these departments  were selected for this study. Other departments were excluded either because drugs were not routinely prescribed or because only a few varieties of drugs were routinely prescribed. Thus, the PSRs are likely to interact less with doctors from the excluded departments.A questionnaire was developed by the authors from previous studies that evaluated the influence of drug promotion on prescribing practices of doctors in developed , 20 and The questionnaire was in three sections. The first section focused on the demographics of the doctors; the second section asked doctors to indicate their response to a series of statements about their sources of information for prescribing and extent of their interactions with PSRs, in each case a typical five-level Likert item was used. The third section focused on the perception of doctors on the reliability of PSRs and pharmaceutical materials as a source of prescribing information and how these factors would influence their prescribing behaviour. This last section also contains series of statements requiring responses using the five-level Likert item as it applied to the second section.The questionnaire was piloted among 10 doctors at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria and, after minor modifications; it was administered to the study population at UCH. Only the doctors who were willing to voluntarily participate were recruited for the study. The questionnaire was allowed a maximum of one week with each participant so as to allow enough time for the filling. In order to increase the response rates, the participants who were unable to produce the previous copy of the questionnaire were given a new one to be filled-in and returned on the spot. All the questionnaires were completed anonymously. Confidentiality of the information tendered was assured to the participants.The ethics committee of UCH Ibadan approved the study.The data obtained were analysed with SPSS version 15. Results were presented as median with inter-quartile range (IQR) for time related variables and as frequencies, percentages, and pictorial diagrams for responses to the questions in Likert-items.One hundred and sixty three (40.8%) of the 400 doctors working at the UCH Ibadan participated in the study. The characteristic features of the respondents are shown in Amongst the respondents who utilized each of the drug information sources, their frequency of use is as indicated in Multiple responses to the statements in the third section of the questionnaire were also observed in this study. This section assessed the impact of drug promotion by PSRs on the prescribing behaviours of the respondents. Their responses are as indicated in Less than half of the doctors working at UCH participated in the study. This was probably due to pressure of work on the doctors which did not allow them the time to attend to the questionnaire. However, the relatively small population size (163) of the doctors who participated in this study is similar to the population (137 and 185 doctors) surveyed in other studies from North central and South-eastern Nigeria, respectively , 23.The doctors relied on multiple sources of drug information as indicated by their high responses to each of the questions . SimilarOver half of the doctors would regularly seek drug information from their colleagues compared to less than a half that would occasionally consult reference books. Previous studies have shown that reliance on colleagues was the most highly ranked information source preference by rural and urban primary care doctors in the United States of America , 32 and Over 40% of the respondents occasionally rely on information from pharmaceutical companies or drug promotion forum/product launches. Reliance majorly on these sources for drug information is very rampant in many developing , 23, 26 Another limitation of a self-report study is underestimation of the effect of pharmaceutical promotion on the prescribing behaviour of doctors which are recognised limitations of the previous studies , 17. In Doctors may not be aware of how much they are exposed to drug promotion, thus a self-report study like this may not have appropriately assessed the impact of drug promotion on prescribing behaviour of the doctors. Further studies that would establish causal relationships between exposure to drug promotion and the prescribing habits of the doctors are therefore suggested. The small study population and focusing on only one institution in Nigeria may limit the generalizability of our results. It is to be hoped that a national survey that will involve doctors from many hospitals in Nigeria would address these problems in the future.Reliance on a wide range drug information resource is commonly practiced by the respondents. The use of potentially inappropriate information resources remains a major challenge facing the respondents and of concern for rational prescribing. Interventions in the form of continuous medical education may be required to improve their information-seeking behaviours. It is self-reported by the respondents that pharmaceutical companies influenced their prescribing behaviour. Measures may be necessary to minimize interactions between PSRs and the respondents.


Studies show that the association between socio-economic status (SES) and self-rated health (SRH) varies in different countries, however there are not many country-comparisons that examine this relationship over time. The objective of the present study is to determine the effect of three SES measures on SRH in 29 countries according to findings in European Social Surveys (2002–2008), in order to study how socio-economic inequalities can vary our subjective state of health. In line with previous studies, income inequalities seem to be greater not only in Anglo-Saxon and Scandinavian countries, but especially in Eastern European countries. The impact of education is greater in Southern countries, and this effect is similar in Eastern and Scandinavian countries, although occupational status does not produce significant differences in southern countries. This study shows the general relevance of socio-educational factors on SRH. Individual economic conditions are obviously a basic factor contributing to a good state of health, but education could be even more relevant to preserve it. In this sense, policies should not only aim at reducing income inequalities, but should also further the education of people who are in risk of social exclusion. Social and economic circumstances have an impact on our physical and mental health. Evidence has shown that the higher the socio-economic status (SES), the lower the prevalence and/or incidence of health problems, illness, disease and death ,2. The rHowever, there are not many country-comparisons that examine the impact of SES on SRH over time. Most studies have been limited to comparing a small set of countries and usually analyzing one year in a transversal design that cannot describe variations due to diverse effects over time . MoreoveOn the other hand, while many studies are focused on economic determinants of health in Europe, there is still a lack of studies trying to explain these inequalities using social factors ,16,17. IIn order to respond to these questions, the main objective of the present study is to compare the effect of different measures of SES on SRH in 29 countries according to European Social Surveys (ESS) during the period 2002–2008. That is, the purpose of this study is to examine how socio-economic inequalities can vary our subjective state of health over time, and thus shed light on future trends. In order to explain the differences in net SRH between European countries, an analysis has been performed on a cumulative dataset comprising the four waves of the European Social Survey  . This daThe dependent variable is the self-rated general state of health (SRH) which was included in the ESS questionnaire in question C7 , with a 5 likert-point answer . et al. [i.e., SES measures) were included in the analysis. There were three variables: income, education and occupational status (see descriptive statistics in http://ess.nsd.uib.no/), although this variable is treated as continuous by taking the midpoint of each banded category [According to Hanibuchi et al. , differecategory . Educaticategory . The ISEcategory . This vaOnce the statistical relevance at the bivariate level had been determined between the three predictors and the dependent variable, the ordinal regression model was carried out. These variables had been standardized previously in order to enable statistical comparisons.The SRH mean values for the four years have been mapped for each country in a Geographic Information System to allow better visualization of the results per country. Map intervals have been delimited by natural breaks, where the cut-offs are defined by seeking natural groups in the data distribution. The GIS searches the lower points in the histogram of SRH means which delimit similar values and maximize differences between classes.Given that the response variable is an ordinal category with five possible values, an Ordered Logistic Regression (OLR) model was performed to estimate the effect of the explanatory variables ,27. BranAccording to Greene , the modx1: Income, x2: Education, x3: Occupational Status. As usual, y* is unobserved. What we do observe is:Being y, which are a form of censored data on y*, to fit the parameter vector. We assume that ε is normally distributed across observations, giving the following probabilities:Then the ordered logit technique will use the observations on For all the probabilities to be positive, we must have:R2 ranged between 0.01 and 0.10. Once the models were computed, the goodness of fit test was appropriate and statistically significant. The obtained Pseudo Additionally, in order to facilitate the interpretation of the results, we have included three figures  that desThe impact of education is described in The main characteristic of Southern/Mediterranean and Eastern countries is the comparatively higher relevance of education when explaining the differences in SRH. In line with the general pattern described in Finally, This study provides a comparison between three socioeconomic determinants of health , and describes the evolution in the relationship of these measures with SRH in European countries for the period 2002–2008. In line with previous studies, these results point out the relevance of socio-economic factors in explaining the differences in individuals’ states of health ,10,11,12i.e., Southern/Mediterranean and Eastern/Post-Communist) [i.e., Anglo-Saxon), income-related inequalities are considerably reduced and some cases are not statistically significant in Spain, which is characterized by universal access to the public health system. Thus, income-related inequalities are greater in the United Kingdom, a country characterized by minimal levels of provision and modest social transfers, although this trend is also reproduced in central European and Scandinavian countries. This tendency increased during the period 2002–2008 and it is expected to get even stronger in the last years of the financial global crisis and during the gradual liberalization of European economies [Despite the differences between countries, this study indicates the relevance of education in preserving a good general state of health during the period 2002–2008 [mmunist) ,30. For conomies ,32. On tconomies .Occupational status loses in statistical significance and this effect is weaker that that produced by income and education. Therefore it is difficult to follow a clear pattern that can describe and explain the relationship of this variable with individuals’ subjective states of health. As mentioned, the effect of occupational status is not equally correlated with SRH in all European countries. In fact, this correlation remains clearly positive among Anglo-Saxon and Central/European countries, but negative among Southern and Eastern countries. This negative association evidences how, in these fragmented and less developed welfare regimes, income guarantees are linked to work positions and a higher variation in income maintenance schemes ,34. In oUnlike present budget cuts, the new context of the global financial crisis should demand more education and new distributive policies to avoid not only a decline in individual socio-economic status, but also deterioration in the general state of health of the European population. These findings evidence that, in the current crisis context, there is a need to: (1) continue allocating public social spending on education to reduce health differences; (2) continue reducing both health inequalities generated by income differences and also (3) those related to occupational status and labor markets. Even though the privatization of less efficient parts of European public systems may be needed to increase the flexibility that new global markets demand, current and future policy-making must take into account the complex interaction that is maintained between people’s socio-economic conditions and their subjective general health. Income, education and occupation-related inequalities cannot determine the individuals’ state of health in objective terms, but the lack of these factors is likely to deteriorate our physical and mental condition. Furthermore, it should be highlighted that education, having the strongest association with SRH, seems to mediate the association of income and occupation inequalities. That is, education is a previous step to practice a healthy lifestyle, even for wealthier and upper class people. In this sense, the educational component must be considered a core factor in explaining these health-related inequalities and in reducing them, thereby obliging policy-makers to consider the relevance of this social determinant.-sectional design for each wave of ESS data. Second, our research focuses on individual determinants of subjective general health, though in the future it might be relevant to study the impact of contextual determinants of health inequalities and therefore to include other variables as controls . Third, the period of analysis comprises a series of years of relative stability in the economic market. Thus, in the future it will be important to analyze the effects of the financial and debt crisis and, in some specific cases, there are unreliable estimations due to a lack of data . Taking these limitations into account, it might be relevant to incorporate new ESS waves to extend the period of study, to improve the statistical representativeness of different countries  and therefore the consistency of the results over time; in turn, the effect of the global financial crisis on Europeans’ state of health could be specifically analyzed.We face three main limitations in interpreting our results. First, there is a problem of causation in the actual relationship between the independent variables and the dependent variable when using crossThis work analyzes the current evolution in the relationship of three SES measures and SRH in 29 European countries for the period 2002–2008. As we have shown, in this period individual economic conditions are indispensable factors to enjoy a good state of health, but education seems to still be a more important determinant of our subjective well-being, even despite the decrease described in its association with SRH in the period studied. That is the reason why new European policies should not only aim to reduce economic inequalities, but also to increase the education of people, which can actively contribute to maintaining a good state of health. Of course, taking into consideration the current context of the global financial crisis, we must be cautious since the relationship between income and SRH has been increasing in recent years. This study shows that education plays a crucial role in improving our health, but the data that we use do not capture the worsening of the economic situation in the last years, in particular in the South of Europe. In fact, it is relevant to notice how the relationship of income with SRH increases slightly during these years and possibly this association will grow in a context of socioeconomic polarization. Despite the fact that the European Union has tried to reduce health inequalities, these differences still persist. Income-related health inequalities have not disappeared for the most part, and have actually increased in the period 2002–2008. In this sense, specific attention still has to be paid to the socioeconomic factors that determine people’s state of health, especially in those mechanisms that reproduce the poor health of excluded groups and/or individuals living in risk of social exclusion in Europe.


Tropical infectious diseases are called neglected, because they are, inter alia, characterized by an R&D deficit. A similar deficit exists for rare (orphan) diseases which neither promise a sufficient return on R&D investment. To encourage the development of treatments for rare diseases, orphan drug acts were created which contain financial and non-financial incentives for the pharmaceutical industry. Similar instruments aimed exclusively at neglected diseases do not yet exist. Proposals for a regulatory approach to promote R&D for neglected diseases include the application of selected orphan drug incentives, or the implementation of a Medical Research and Development Treaty (MRDT) with national funding obligations for medical R&D. We compiled and analyzed experts' opinions on causes for the treatment deficit for neglected diseases and on desirable and feasible measures to promote neglected disease R&D. Hereby, the focus was on mechanisms contained in orphan drug regulations and in the Medical Research and Development Treaty draft . Lastly, we solicited experts' opinions on the desirability and feasibility of a regulatory instrument to foster R&D for neglected diseases.An international online-Delphi survey was conducted with 117 (first round) and 56 (second round) experts of different professional backgrounds and professional affiliations who formulated and ranked causes and solutions related to the treatment deficit for neglected diseases.In both rounds of survey, the majority of the participating experts  advocated the development of a regulatory instrument to promote R&D for neglected diseases. Most experts  also considered this to be a feasible option. With the exception of market exclusivity, which was viewed critically, key provisions contained in orphan drug regulations were judged favorably also for neglected diseases. A majority  supported national funding obligations for neglected diseases which are proposed by the Medical Research and Development Treaty draft.While not all features of orphan drug regulations and of the MRDT draft received equal support, the view was expressed that a regulatory instrument would be a desirable and feasible measure to promote R&D for neglected diseases. Common features of neglected diseases include their prevalence in poor populations in developing countries, their cause for stigma and discrimination, their high impact on morbidity and mortality and their relative neglect in terms of research and development activities. For some neglected diseases, tools are available to control, prevent or possibly eliminate them. For other so-called tool-deficient diseases, such tools are still lacking ", "[...] the questionnaire for the second round will be five to ten times that of the first round.", acknowledging that the items that were contributed later do not receive the same treatment as those listed from the beginning of the survey  interesting and helpful for policy development" or: "Very interesting and useful. I guess sometimes one would like more nuanced options for a more appropriate answer".As we have shown in the first paragraph of the Results section, the sample was not balanced in terms of professional backgrounds, professional affiliations or the place of residence. The aim of the survey was to gather as broad a spectrum of perspectives as possible. The sample selection was purposive insofar as we chose specific sources from which to gather a panel of interested experts, such as relevant publications, conferences, hearings etc.. Prior to the first round of the survey, we could only assume the distribution of experts in the demographic categories. Since it was impossible to predict participation and attrition rates at the onset of the study, we did not attempt to reduce and adjust the initial panel to represent a balanced sample. We do not dare to anticipate how and if the results of the study may have differed if the panel had been more balanced. However, we observed variations within groups in cross-tabulations which suggest that the assessments made by the experts may not necessarily be linked to professional affiliations.The survey facilitated the quantification and correlation of views far beyond what can be reproduced in this paper. Its outcome underlined that insufficient funding for R&D for neglected diseases is one of the most important causes for the treatment deficit. Yet it is by no means the only important cause: there was only one item (no/ineffective drugs for NDs) in the first round, and two items (no/inadequate research coordination and disease-specific research difficulties) in the second round that received less than 80% of aggregated positive responses (most important/important) by all participating experts. Similarly, while respondents from all professional affiliations chose funding issues as most important in the first round, they suggested 98 additional items, which formed the basis for the extension of the list of causes in the second round. Consequently, funding issues became one of several causes that received high priority in the different professional affiliations. This process and its outcome underline the complexity of the issue and the need to uphold multifocal strategies that will increase awareness, reduce poverty, adjust R&D priorities to include NDs, increase and sustain public and private sector funding, and promote health as well as research infrastructure in endemic countries.Certainly, no single mechanism or regulatory instrument can cover this broad range of challenges. The participants of the survey offered a diversity of comments on the desirability and feasibility of a regulatory instrument, including: "This is a purely national decision unlikely to be easily introduced into legislative bodies, but definitely worth trying. Once a few countries install some such instrument others will follow."; "would best be done under the auspices of the WHO, would cover all aspects from discovery to delivery, with follow up monitoring"; "We have too much regulation already and implementation on a global basis is simply not practicable".Various modifications to orphan drug laws for the benefit of NDs have been suggested in recent years such as transferable market exclusivity ,35, or tThe respondents were not asked, however, to assess orphan drug acts or the MRDT for neglected diseases as such. This, on the one hand, precludes a comprehensive answer to the question of their desirability and feasibility for ND research and development. On the other hand, the separation of individual measures from specific regulatory instruments was part of the survey's concept to enable us to learn which measures are attractive and practicable in the eyes of the respondents. It may thus be of interest to carry forward, expand and focus the research, perhaps with a similar methodology, to engage experts and stakeholders in determining which measures could contribute to a future instrument to promote R&D for neglected diseases.The treatment deficit for neglected diseases can neither be attributed to a single cause, nor can it be remedied by a single measure. Both orphan drug acts and the MRDT are controversial approaches to promoting neglected disease R&D. The ongoing debate on the two concepts points to a strong interest in a regulatory instrument, which we could confirm in our Delphi survey. Such instrument may not rely on the same incentives as orphan drug regulations, or completely restructure medical R&D funding as proposed in the MRDT. Still, if it included mechanisms to provide sufficient and sustainable funding for effective, affordable and field-sensitive diagnostics and treatments, facilitated research cooperation and increased awareness for NDs on health policy agendas, it would express the same political will to guarantee equitable health care for patients with neglected diseases as orphan drug regulations intended for patients with rare diseases.It is recommended that a Policy Delphi is followed by a working group which may utilize the results to formulate relevant policy recommendations.  The dataThe authors declare that they have no competing interests.AF, PT and OR conceived of the survey, and participated in its design and coordination. AF implemented the survey and performed the statistical analysis. AF, PT and OR drafted, read and approved the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/11/312/prepubQuestionnaire Round I. Questionnaire of the first round of the Delphi survey.Click here for fileQuestionnaire Round II. Questionnaire of the second round of the Delphi survey.Click here for file


We discuss how these advances might improve the diagnosis of this skin cancer and point out the present capabilities and limitations of the method.The incidence of malignant melanoma, the most dangerous form of skin cancer, is rising each year. However, some aspects of the tumor initiation and development are still unclear, and the current method of diagnosis, based on the visual aspect of the tumor, shows limitations. For these reasons, developments of new techniques are ongoing to improve basic knowledge on the disease and diagnosis of tumors in individual patients. This paper shows how electron paramagnetic resonance (EPR), a method able to detect free radicals trapped in melanin pigments, has recently brought its unique value to this specific field. The general principles of the method and the convenience of melanin as an endogenous substrate for EPR measurements are explained. Then, the way by which EPR has recently helped to assess the contribution of ultraviolet rays (UVA and UVB) to the initiation of melanoma is described. Finally, we describe the improvements of EPR spectrometry and imaging in the detection and mapping of melanin pigments inside  Malignant melanoma is a skin tumor characterized by the uncontrolled proliferation of melanocytes. This tumor is the most dangerous form of skin cancer and is responsible of 3 of 4 deaths linked to a skin cancer. The incidence of malignant melanoma is rising each year , 2, and,The abilities and perspectives of EPR spectrometry and imaging as a detection method for melanin pigments, and consequently for pigmented melanomas, will be also discussed. Indeed, for now the only method used by dermatologists for suspecting melanoma is an optical examination of the lesion based on the detection of five factors: Asymmetry, irregular Borders, nonhomogenous Color, large Diameter, and Evolving . This optical examination, even if effective, shows limitations: it does not provide any information about the penetration of the tumor in the skin, which is a crucial factor to determine the growth state of the potential melanoma and to provide an adapted treatment. The use of EPR imaging for the mapping of free radicals trapped in melanin might allow filling in this lack of spatial information in a noninvasive way.melanos that means “dark”. The origin of this name is generally attributed to the Swedish chemist Berzelius [Melanin is the most widespread pigment in the epithelia of vertebrates. This molecule is responsible of the pigmentation of skin, hair, and eye. Historically, its name comes from the Greek word erzelius . As explerzelius , the tererzelius , while perzelius . Howevererzelius , 12. The melanin polymer has some interesting properties among which light absorbance, redox properties, and chelating properties . The widElectron paramagnetic resonance (EPR) is a magnetic resonance method similar to nuclear magnetic resonance (NMR) which focuses on the detection of paramagnetic materials. The paramagnetism notion refers to the behavior of a material substrate that does not possess spontaneous magnetization but, under an external magnetic field, acquires a magnetization parallel to this magnetic field. This phenomenon, explained by the quantum physics principles , resultsAlthough the EPR technique is similar to NMR, there are two notable differences between them . First, in vivo EPR spectra are mostly obtained through continuous wave (CW) experiments, whereas, in clinical MRI, results are always obtained with the use of pulsed radiowave. Second, compared to MRI, EPR imaging requires a gradient field at least one order of magnitude greater.The second major difference between EPR and NMR comes from the difference of their relaxation time, which is in the range of nanoseconds for electron and in the range of milliseconds for proton. This has two consequences: first, in vivo [in vivo [During the last 60 years, EPR spectrometry has been successfully used in many parts of the scientific research, especially in biology where it contributed to the understanding of a large number of physiological processes. The fields where EPR has been the most used and useful already possess their own review(s), such as the study of iron-containing molecules , the assin vivo , 20, or [in vivo .A more recent method derived from EPR spectroscopy, called EPR imaging, consists in adding an external gradient field that modulates the resonance frequency of the paramagnetic species in function of their position in space , 23. As Because in 1954, melanin was found to contain stable free radicals detectable by EPR  and thatAn excellent extensive review of this topic  has been published by Lund and Timmins in 2007 . We brieThis role of melanin was put in evidence when Sarna and Sealy demonstrated that the exposition of melanin to UV and blue light generates reactive melanin radicals (RMRs). Moreover, it was demonstrated that RMR could react with biomolecules and molecular oxygen , 40 to lin situ in skin. This method was used to assess quantitatively the RMR formation in function of the exposition to different wavelength in the skin of a mouse model for which the action spectrum was already known [An EPR technique was recently developed by Wood et al.  to enabldy known . They obThese results still have to be confirmed on other animal species (including human), and we can predict that the controversy about UVA, UVB, and melanoma is far away from the end, but these preliminary results could bring the outcome faster than expected.The first important work concerning the quantitative detection of melanin by EPR spectrometry inside melanoma samples was published by Elek et al. in 1980. When measuring ocular melanomas embedded in paraffin, they observed a free-radical signal situated at g-factor = 2.003, corresponding to the EPR signal of melanin . When coex vivo melanoma [in vivo three years before by injecting a paramagnetic nitroxide contrast agent [This study was followed in 1990 by Katsuda et al. who adapted a self-made EPR cavity to an EPR imaging device and managed to get the first EPR image of endogenous pigments inside melanoma . Howeverst agent  near theIn 2005, after many years of work using EPR to study the properties of melanin and the effects of UV's on melanin and melanoma development, Timmins had the premention that EPR imaging could be helpful in the melanoma diagnosis and submitted a patent for the general concept of “detecting melanin by EPR” .In 2008, Vanea et al.  assessedIn the same study, they adapted their method to the measurement of paraffin-embedded human melanomas. As a result, they were able to correlate EPR images of these human melanomas with contiguous histological sections coming from the same tumors Figures  and demoin vivo of a large mouse melanoma B16 model, using a low microwave frequency EPR imager. This image was the first EPR image of the endogenous melanin pigments inside of an in vivo melanoma  technique and their EPR spectra , 46. In in vivo, while EPR measurements were performed ex vivo. By comparing the two methods, it was moreover demonstrated that EPR spectrometry was more accurate than BLI in terms of assessment of the tumoral growth level. These results, even if very encouraging, might however be moderated as BLI measurements were performed μg of melanin could be detected ex vivo in favorable conditions using X-Band EPR spectrometry . The detection threshold was however around 103 times higher for L-Band and measurements . Consequently, the performances of the method should still be improved to allow accurate and sensitive measurements in vivo.Finally, the limit of detection of the method in the present configuration (EPR Bruker E540 Elexsys equipped with a super high-sensitivity probe for X-Band (9 GHz) measurements and equipped with an E540R23 L-B and EPR head-coil resonator for L-Band (1.1 GHz) was assessed. This experiment, made in parallel with synthetic melanin and melanoma powder, allowed us to determine that such a tiny quantity like 2 For approximately fifty years, considerable progresses were performed in the field of melanin and melanoma knowledge. These progresses are notably due to advances in biochemistry, genetics, and molecular biology. Parallel to these advances, technological developments in the field of magnetic resonance were achieved so that, nowadays, it is possible to apply the electron paramagnetic resonance spectroscopy and imaging to the detection of biological-free radicals, including those trapped in melanins, with a high sensitivity.The application of EPR to melanins has led to many discoveries concerning melanin structure and melanoma development. As shown by Lund and Timmins , EPR spein vivo mapping of endogenous melanin pigments inside melanoma could recently be achieved by EPR imaging. Ongoing researches are now focusing on the characterization of human melanoma samples by this technique. Indeed, the diagnosis of melanoma in human by the ABCDE optic rule, even if effective, does not refer to any objective quantifiable standard. Moreover, an important limitation of the technique is the impossibility to obtain information about the tumor penetration (Clark's index) without performing a biopsy. The use of EPR imaging could fill in these lacks, that is why this method is at present tested on ex vivo human melanoma samples with different Clark's index. Applied in vivo, it would help the surgeon to define more precisely the margins for lesions resections, based on a noninvasive method. Preliminary results are encouraging, but it seems that early melanomas could provide an EPR signal that is insufficient for the reconstruction of EPR images. If these results are confirmed, new technical improvements in terms of magnetic gradient field or EPR cavity should be required before adapting the method to in vivo measurements.On the other hand, the improvements achieved in the field of EPR spectrometry during these last years allowed us to measure accurately and sensitively the presence of melanin pigments inside melanoma samples. As a straight correlation was found between the intensity of the EPR signal of melanin and the tumor growth state, the signal of melanin appears as a good indicator for melanoma development. Moreover, due to a continuous improvement of EPR imager performances, the first


A recent report by the Institute of Medicine leaves few urgent reasons standing for the continued use of chimpanzees in biomedical research. It is high time to think about their retirement, Frans de Waal argues, without neglecting prospects for non-invasive research on behavior, cognition, and genetics. Pan troglodytes), some of which required special precautions and care as they had been infected with HIV or hepatitis C.When New Zealand, in 2000, became the first nation to pass legislation against research on the great apes, and Spain adopted a resolution to grant these animals legal rights, both decisions were hailed as substantial progress even though neither country conducted any actual ape research. I could not resist remarking to a Spanish journalist that I would have been more impressed had they abolished bullfighting. It is only when the Netherlands and Japan passed similar laws that the movement to improve the status of apes began to make a difference, because both countries outlawed what they had been practicing. With euthanasia ruled out as a means of population control, both governments faced the expensive need to find a home for ex-laboratory chimpanzees  gave in to pressure regarding a planned move of chimpanzees from the Alamogordo Primate Facility in New Mexico to the Texas Biomedical Research Institute in San Antonio. The move would have meant a return of about 200 semi-retired chimpanzees to research. NIH asked the Institute of Medicine (IOM), an independent advisory board associated with the National Academy of Sciences, to explore how critical chimpanzees still are for biomedical research The NIH's head-in-the-sand attitude towards ethics hinted that powerful interests were at play, which in turn explains the IOM's decision to keep chimpanzee experts off its committee. This way, no established interests were represented and the discussion was free from political interference. The result, though, was a committee with only tangential knowledge of the species under consideration. From the start, therefore, the committee faced serious challenges and pressures, and it is in this light that its final report is to be commended for the balance it struck and the high-quality information it delivered.useful for biomedical research, but whether they are critical is in doubt. The time has come to get ahead of the “trajectory” discerned by the committee, and permanently halt all invasive research on this species.The IOM committee did an outstanding job reviewing and summarizing the biomedical need for chimpanzees in a report entitled “Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity”, released December 15, 2011 If the NIH are not ready for such a step, they should at least convene a committee of philosophers and bioethicists to gather diverse opinions about the ethics of continuation of current practice. It is a complex issue P. paniscus) plays a central role as touchstone of what sets us apart as a species. Knowledge of our closest living relatives also helps determine which human capacities likely have a long evolutionary history. The general trend over the last few decades has been a narrowing of the gap, bringing increasingly complex capacities under the umbrella of our primate heritage. Species-typical human characteristics remain undeniable, however, and there is a great need for continued cognitive testing and studies of genetics, neuroscience, and development to add evolutionary context to findings on human behavior. Without this kind of research, the social sciences, the humanities, and philosophy would still live in the illusion, as they did a few decades ago, that humans are totally unprecedented. Anyone who has followed the literature realizes that the vast majority of mental and behavioral differences with other animals are quantitative rather than qualitative.The IOM report supports the great value of chimpanzee research that is minimally harmful or painful, specifically comparative genomics, behavioral and cognitive studies, and neuroimaging. We could add postmortem tissue and brain analysis of apes that have died of natural causes. The chimpanzee  was released together with fellow apes who lacked such knowledge. The others adopted the same body language as their knowing comrade, and the concept of Theory-of-Mind was born My personal definition of non-invasive research on apes is simple: the sort of research I would not mind doing on human volunteers. This would include all sorts of cognitive testing, trained giving of  blood samples, behavioral observation, and voluntary neuroimaging. The last procedure is not yet available for apes, but likely to be developed in the near future. It is time to get a productive research program on chimpanzees off the ground without funding agencies holding its noninvasive nature against it. All they would need to do is recognize that ape research is equally constrained as ongoing human research. By continuing research that places human behavior in an evolutionary light, we would also be returning to the original rationale for bringing apes into research settings. In the 1920s, Robert M. Yerkes was the first to acquire great apes for research in the US, and his sole objective was to understand their behavior, cognition, and temperament The inevitable implication of the IOM report and the NIH's decision to momentarily halt all funding for chimpanzee-related projects is an increased focus on retirement and improved housing conditions. The report speaks of “ethologically appropriate” environments for chimpanzees, but fails to define what this means for a highly social species. Current conditions range from least to most appropriate: a) single or pair housing, b) small group housing in metal/concrete runs and primadomes, c) unroofed large outdoor corrals with grass and climbing frames, and d) multi-acre forested habitats . In ordeThe three main recommendations of the IOM report are a) put a halt to all or almost all invasive biomedical research on chimpanzees, b) a continuation of non-invasive research to evaluate human-ape similarities and differences in genetics, behavior, and neuroscience, and c) retirement and/or improved housing. The first reaction of the NIH has been to take these recommendations seriously. Being mindful of the quote from Wolfgang Goethe featured on IOM reports , this nation can expect substantial changes in its treatment of apes as a result of the overdue recognition of their special moral status.Time featured him in 2007 as one of the World's One Hundred Most Influential People. He is C. H. Candler Professor of Psychology at Emory University and Director of the Living Links Center at the Yerkes National Primate Research Center.Dr. de Waal received his PhD in Biology and Zoology from Utrecht University, the Netherlands, in 1977. He completed his postdoctoral study of chimpanzees while associated with Utrecht University, in 1981, and moved the same year to the United States. He has been a National Academy of Sciences member since 2004, and a Royal Dutch Academy of Sciences member since 1993.