There are increasing evidence highlighting the importance of incorporating issues of global health into pre- and post-graduate medical curricula. Medical international cooperation is a fundamental component of strategies to include global health issues in post-graduate medical curricula.Here we describe a seven-year cooperation between the Non Governmental Organization (NGO) “Doctors for Africa CUAMM” and the Pediatric Residency Program (PRP) of the University of Padua  that offers residents a well-articulated personalized international child’s health (ICH) elective in Africa, called “Junior Project Officer”. The elective includes: a careful candidate selection process; pre-departure educational course; preceptorship in Padua and Africa, personalized learning objectives, a personalized job description, a six-month hands-on learning experience in Africa, evaluation of the experience, and formal private and open feed-backs/reports.Between 2006 and 2012, 14 residents aged from 27 to 31 years, six attending the III, nine the IV and two the V year of residency completed the six-month stage in Africa. All worked in pediatric in-patient units; seven also worked in out-patient clinics, six in emergency rooms and seven in community health centers. Eleven were involved in teaching activities and four in clinical research projects. All residents claimed to have achieved their learning objectives.A strong partnership between the NGO and the PRP, and well-articulated personalized learning objectives and job description contributed to a successful ICH elective. There is increasing pressure to incorporate issues of global health into pre- and post-graduate medical curricula in order to provide new generations of doctors with a multicultural perspective on health care-3. The NDespite the relevance and benefits of programs offering ICH electives, and despite numerous recommendations and guidelines on how to build them-12 majorBetween 2006 and 2012, the Pediatric Residency Program (PRP) of the University of Padua  joined the Junior Project Officer (JPO) program promoted by the Italian non-governmental organization (NGO) “Doctors with Africa CUAMM (Collegio Universitario Aspiranti e Medici Missionari)”, which oCUAMM, the first NGO in the field of healthcare to be officially recognized in Italy, is the largest Italian body working to improve and safeguard the health of African populations. The organization has long-term goals, and provides quality healthcare services that are open to all. Its philosophy is to help Africa by creating, supporting and promoting training environments and to create within the international medical community a culture open to global health issues. It is present in seven Sub-Saharan African countries: Angola, Ethiopia, Mozambique, South Sudan, Uganda, Sierra Leone and Tanzania. It operates through volunteers, namely, health professionals such as doctors, nurses, midwives, technicians and administrative staff. These volunteers provide support to hospitals, health districts , motor rehabilitation centers, nursing schools, and Medical Universities .The JPO project launched in 2002 offers doctors in training the possibility of a rotation in one of hospitals in Africa in which CUAMM volunteers work. It also aims at eliciting a vocation to work in the field of international medical cooperation. It is directed to residents in Infectious Diseases, Internal Medicine, Obstetrics and Gynecology, Pediatrics, Public Health and Surgery.The PRP of the University of Padua is a 5-year national accredited program for post-graduate training in Pediatrics. Approximately 80% of learning activities takes place in the clinical setting, in which medicine is practiced under the supervision of a faculty member with the goal of increasing levels of responsibilities during training. The remaining learning activities are formal lectures, seminars, workshops. Residents rotate through 15 of the 25 divisions/services of the Department of Woman’s and Child’s Health of Padua and of affiliated hospitals during their first three years devoted to provide general pediatric competences; rotations last between 3 to 6 months. During the last 2 years of training, residents select elective rotations in pediatric subspecialties involving, at most, 3 divisions; each rotation lasts from 6 to 12 months.The JPO elective is open to residents in their third year onwards. Only one resident at a time can go to Africa.Candidates are selected based on their professional profile, notably pediatric knowledge, level of autonomy, manual skills and reliability, and on the results of an interview with members of the Resident Affairs Committee (RAC) and with representatives of CUAMM. The interview is designed to understand the candidate’s motivation join the project, to describe all the potentially negative and positive aspects of the experience and to try to evaluate the probability that the candidate will successfully complete the program.After the initial screening, residents are required to attend a professional training course  organized by CUAMM. This consists of six three-day modules held on a monthly base; the first is devoted to the basic principles of health cooperation with countries that have limited resources and the inspiring concepts of “Doctors with Africa CUAMM”; the second module introduces the basis of “Strengthening Health Systems” and the strategic approach adopted by the NGO in Africa. The remaining modules provide general concepts of hospital management and public health, and information about the diagnostic and therapeutic guidelines established for the main tropical infectious diseases, about the status of mother and child health in Africa, and about the more relevant critical issues and the main programs activated to address them.Once a candidate has successfully undergone the interview and the pre-departure course, the possible destination in Africa is identified, based exclusively on the presence on site of a pediatrician from CUAMM who can function as a local tutor and on safety issues related to the local social and political situation. A preceptor in Padua (one of the authors – LDD), chosen among RAC members because of experience in international medical cooperation and commitment to the JPO project, was assigned to each resident.Once the resident, the hospital in Africa and the CUAMM volunteer serving as local tutor are selected, the overall learning objectives of the training . All his/her activity is carried out under the supervision of the local tutor in Africa.The 6-month ICH elective is counted as any other rotation that is mandatory for residents during their training. Consequently, it is subject to the usual PRP evaluation process, which foresees evaluation of the residents by tutors, and of the quality of the rotation and of the tutors’ performance by residents, based on validate questionnaires. TherefoCUAMM provides participants with the necessary insurance coverage for personal and professional risks, and assistance in applying for VISA and work permits, as required, and lodging on site in residences rented by CUAMM. The residency program covers travelling costs, whereas residents must pay for all other expenses they incur in Africa from the salary they continue to receive from the University.The JPO program is governed by a memorandum of understanding, signed by CUAMM and the University of Padua, according to which the NGO and the University undertake to cooperate to improve the health status of the population in Africa by making available their own specific resources and competences.Before the JPO project started in October 2005, RAC members visited the hospitals chosen for the project. The aims of the site visit was to meet the local political and health authorities, to describe the PRP, to see the hospitals and their facilities in order to acquire an overall sense of the environment where residents are expected to work.Between 2006 and 2012, of the 135 residents who participated in the PRP and were eligible for the JPO, 22 declared their interest in joining the project and attended the preparatory course. One dropped out because she did not feel psychologically prepared, and seven were unable to go to Africa for contingent reasons. Thus, 14 residents went to Africa . Their age ranged from 27 to 31 years; six were attending the III, nine the IV and two the V year of residency. While in Africa, all worked in pediatric in-patient units; seven were also involved in out-patient clinics, six in emergency rooms and seven in territorial health centers. Eleven were also involved in teaching activities for local nurses and doctors in-training, and four carried out a clinical research project while in Africa.As reported in Table To our knowledge, this is the first article to describe the strategic framework of an ICH elective for students enrolled in a European PRP. Furthermore, no other Italian pediatric residence programs offer similar experience based on such an articulated framework. During the seven years that the PRP of Padua University participated in the JPO project, there was always a candidate for the ICH elective. Moreover, all the 14 residents who participated in the elective completed the six-month stage abroad, without having encountered any major problems, which is remarkable given the duration of the stage. Notably, all felt they had undergone an important human and professional experience. Therefore, the JPO project, as carried out by the PRP of Padua University, is a useful example of how to offer ICH electives to pediatricians in training  while in Africa. As witnessed by the residents’ feedbacks, this tutorship was greatly appreciated. The tutorship in Africa was considered equally effective. In the two cases in which the resident did not experience a positive tutorship in Africa, the situations were carefully monitored, and the problems did not prevent the residents from completing their ICH elective and reporting positive comments.The MOU of the University of Padua, within which the PRP operates, is a key factor of our IHC elective. In fact, in this MOU the University of Padua endorses the CUAMM-PRP partnership and thus recognizes the educational value of the JPO project and its impact on society as a whole. Thus, the CUAMM-PRP partnership has the status of an academic endeavor and consequently sets rigorous standards for its development and implementation. The MOU served also to provide the administrative and legal elements necessary to run the project in Padua. Our experience suggests that PRPs offering ICH electives should have a formal, officially recognized (by the authorities governing the PRP) relationship with international medical organizations that are well positioned in countries with limited resources. Such organizations are able to facilitate the access of residents to hospitals in Africa, identify local expert tutors and provide all the resources necessary to support the residents’ presence in Africa. Ideally, they should share CUAMM’s commitment to education.We are aware that such an ICH does not fulfill all the requirements of a complete pediatric global health education. UndoubtFinally, if one of the reasons to offer an ICH was to solicit professional vocations in the field of international medical cooperation, it is noteworthy that two of the residents who participated in the ICH are currently involved in programs of international medical cooperation (and one of them with CUAMM).In conclusion, we decided to make the pediatric community aware of the model we used to offer an ICH elective with the aim of stimulating a debate on this matter and of generating criticisms and ideas. This, in turn, might encourage other PRPs to offer ICHs to residents. Indeed, more should be done to implement the culture of medical global health in medical post-graduate programs. It is important to raise future generations of doctors with the concept that we live in a world of strong inter-dependency where everyone should practice medicine in the part of the world in which they work but with their gaze directed to wider horizons.ICH: International child health; JPO: Junior project officer; MoU: Memorandum of understanding; NGO: Non Governmental Organization; PRP: Pediatric residency program; RAC: Resident affairs committee.All authors declared no competing interest with the contents of the manuscript.LDD: Among the ones conceiving the MPO project for the Pediatric Residency Program of Padua; intervened in collecting the data of the experience, analyzing them and in writing the paper; preceptor in Padua for the residents in Africa. GPer & EB: Past and present chairman of the Pediatric Residency Program of Padua, they intervened in supporting the JPO project, in analyzing the data and in writing the manuscript. DC & GPut: the Founder of the JPO project in Italy; they intervened in supporting the JPO from the CUAMM size, in supervising the analysis of the data and of the manuscript. AG: Chair of the organizing committee of the JPO project, she intervened in developing the capturing forms for analyzing the data regarding the experience, in data managing and in formulating the first set of analysis. All authors read and approved the final manuscript.DC, MD, Director, Doctors with Africa CUAMM, Padua, Italy. EB, Full Professor of Pediatrics, University of Padua, senior member of the Resident Affair Committee; Chair of the Pediatric Residency Program of Padua University since October 2012. LDD, Associated Professor of Pediatrics, University of Padua, Chair of the Pediatric Divisions, expert in post-graduate medical training; Vice-Chair and senior member of the Resident Affair Committee of the Paediatric Program of Padua. AG, JPO Project Manager – Human Resources Department, Doctors with Africa CUAMM, Padua, Italy. GPer, Full Professor of Pediatrics, University of Padua, Director of the Department of Woman’s and Child’s Health of the University of Padua, Italy; Chair of the Pediatric Training Program from 2005 to September 2012; presently member of the Resident Affair Committee. GPut, MD, Head of Planning, Doctors with Africa CUAMM, Padua, Italy.


DEAS is an on-going population-based, representative survey of community-dwelling people living in Germany. The survey started in 1996, and the fifth wave will be conducted in 2014. It comprises cohort sequential data, i.e., both repeated cross-sectional surveys and panel data for people aged 40 and over.How healthy are people as they age, what are possible causes and consequences, and what can be derived from this with a view towards health promotion in older people? The German Ageing Survey, funded by the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (DEAS; To date, DEAS has considered people born between 1911 and 1968, and over 14,700 participants have been interviewed face-to-face and been given written tests and questionnaires. The survey aims at knowing more about the living conditions and the quality of life of people in middle-age and later life, and at knowing more about changes over time, both on the individual and the societal level. Thus DEAS covers a large range of subject areas, including family and social networks, work and retirement, participation, economic situation, well-being, psychosocial resources, as well as health and health behaviour. The data allow both the analysis of individual health trajectories and health changes on the societal level: How healthy will older people be in the next years or decades? For this purpose, different birth cohorts can be compared that have reached the same age at different points in time.The present findings suggest that birth cohorts born later report less illnesses, lower ailments and higher physical activity, which points to better health and health behaviour of subsequent cohorts. Overall, these findings are in line with those from other surveys in Germany, though the comparison of different studies is limited. One reason for this is the use of different health indicators, which is perhaps most evident in the measurement of chronic illnesses and multi-morbidity. Additionally, other factors such as the in- or exclusion of very old or institutionalised people and the use of cross-sectional surveys versus panel data might contribute to heterogeneous findings on health trends.For the study of health trends in ageing societies, multiple health indicators are needed to allow for the fact that differences between various health components become more pronounced in later life. Aiming at harmonising concepts and instruments to assess healthy ageing, as initiated by the Robert Koch Institute, is therefore highly appreciated.


The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes  such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL) and zoonotic visceral leishmaniasis (ZVL). The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming. L. donovani complex, order Kinetoplastida. The aetiological agents are: L. donovani in India and Central Africa and L. infantum in the Americas, the Middle East, Central Asia, China and the Mediterranean. The human disease is lethal if not treated early after the onset of clinicopathological abnormalities that include: malaise, anaemia, cachexia, hypergammaglobulinaemia, hepato-splenomegaly and progressive suppression of the cellular immune response. L. donovani complex species are intracellular parasites of macrophages of lymphoid organs such as the spleen, lymph nodes, bone marrow and liver. Their biological cycle alternates between the amastigote form in the vertebrate host and the promastigote form in the gut of the sandfly vector. More than 90% of human cases of VL occur in India, Sudan, Bangladesh and Brazil. Each year 500,000 new human cases of VL are reported .L. donovani and involves a severe parasitism of the blood and skin and an anthropophilic vector, making man the reservoir of the disease. In contrast, ZVL with dogs as reservoir hosts is usually associated with L. infantum and is found in the Americas, the Middle East, Central Asia, China and the Mediterranean. ZVL is considered a canid zoonosis in which sandflies become infected mostly by feeding on the skin of canids and humans are the final host of the parasites. Blood-parasitism in people with ZVL was at first considered not to occur . In Eureservoir  or in oreservoir  and in ceservoir .L. infantum infection with increasing age of dogs . Explaiiewed in ,20 Sanch .P. perniciosus than of L. longipalpis , but vesing BCG  or muramsing BCG  adjuvantsing BCG . The vacpressure . There inine ZVL . Leishmu to 2006 . In Araçcampaign .® has also been licensed in Brazil. It is composed of the recombinant A2-antigen of Leishmania amastigotes and is adjuvanted by saponin , explaiiewed in -82 and riewed in , 85 84]® has alsiewed in ; immunotiewed in  and 24 diewed in ; and in iewed in , there icontrols . There icontrols  and the Leishmania-infected dogs are thought to reside in Italy, Spain, France and Portugal as determined by published serological surveys from those countries [Leishmania vaccine is due to be released in selected countries endemic for the disease [While in Brazil an average of 4,000 human cases of ZVL is reported annually, in Europe, the incidence of human ZVL is relatively lower, with a total of approximately 700 reported new cases per year for all southern European countries . An estiountries . Autochtountries  northernountries , north wountries  and soutountries . The Eurountries . In soutountries ,94 is prountries -97. In tountries . In 2011 disease . It willIn Iran, ZVL is not controlled by serological testing and culling infected dogs, but by the use of deltamethrin-impregnated dog collars. These measures were reported to reduce the risk of infection in dogs by 54% and in children by 43% .Leishmania infection in the domestic dog population is fundamental in order to avoid the spread of ZVL between dogs and man. A high level of infection in dogs, particularly in impoverished areas, is often recorded just before the start of a human epidemic and may be an important predictor of an impending outbreak of disease in the human population [The control of pulation . It is cThe One Health concept is a worldwide strategy for expanding interdisciplinary collaborations and communication in all aspects of health care for man, animals and the environment. As monitoring of ZVL in companion animals is extremely important for the control and prevention of the human disease, ZVL is one of the best examples of a disease whose successful control and eradication depends upon the use of a One Health strategy.The authors declare that there is no conflict of interest regarding the present work and that sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.CBPS did the review of the literature and wrote the article. MJD conceived the idea of the article as part of the work of the WSAVA One Health Committee and critically reviewed the article. Both authors read and approved the final manuscript.


Interval timing (IT) is an essential capability of living organisms from invertebrates to humans that allows them to accurately estimate durations in the range of seconds to minutes. In peak interval procedure ,2 subjecWe implemented a minimal Striatal Beat Frequency (SBF) model ,6, that The states of all OSC neurons determine the vector of state that is received by each spiny neuron together with the vector of state of OSC stored in MEM at CT. In our implementation, the output is generated through coincidence detection, i.e., dot product, between the current state of OSC and the state of OSC stored in MEM at CT. Biological noise induces different types of variabilities, e.g., random fluctuation in the frequencies of OSC neurons, errors in storing/retrieving the criterion time in MEM, etc. We investigated both analytically and numerically the properties of the output function generated by the SBF model and found that: (1) in the absence of any variability in the parameters of the SBF model, the width of the output function that measures the spread of behavioral responses is constant, therefore, violating the scalar property, (2) if variability is allowed, for example in the memorization/retrieval of CT, then the output function of SBF model is always Gaussian, which is a consequence of the central limit theorem, regardless of the probability distribution function (pdf) of fluctuating parameter. Moreover, we found that the scalar property is also preserved regardless of the pdf of fluctuating parameters.


Rx for Change to provide a comprehensive, online database of the evidence for strategies to improve drug prescribing and use.Globally, suboptimal prescribing practices and medication errors are common. Guidance to health professionals and consumers alone is not sufficient to optimise behaviours, therefore strategies to promote evidence-based decision making and practice, such as decision support tools or reminders, are important. The literature in this area is growing, but is of variable quality and dispersed across sources, which makes it difficult to identify, access, and assess. To overcome these problems, by synthesizing and evaluating the data from systematic reviews, we have developed We use reliable and valid methods to search and screen the literature, and to appraise and analyse the evidence from relevant systematic reviews. We then present the findings in an online format which allows users to easily access pertinent information related to prescribing and medicines use. The database is a result of the collaboration between the Canadian Agency for Drugs and Technologies in Health (CADTH) and two Cochrane review groups.Rx for Change currently contains over 200 summarised reviews, structured in a multi-level format. The reviews included in the database are diverse, covering various settings, conditions, or diseases and targeting a range of professional and consumer behaviors.To capture the body of evidence on interventions to improve prescribing and medicines use, we conduct comprehensive and regular searches in multiple databases, and hand-searches of relevant journals. We screen articles to identify relevant systematic reviews, and include them if they are of moderate or high methodological quality. Two researchers screen, assess quality, and extract data on demographic details, intervention characteristics, and outcome data. We report the results of our analysis of each systematic review using a standardised quantitative and qualitative format. Rx for Change is a novel database that synthesizes current research evidence about the effects of interventions to improve drug prescribing practices and medicines use. The safe and effective use of medicines is an important aspect of quality healthcare. While there is an abundance of data on the clinical effectiveness and safety of various drugs, this does not ensure that the drugs are being appropriately prescribed or taken; in fact, suboptimal prescribing and medication errors are common across countries . ResearcRx for Change http://www.rxforchange.ca.To address these problems, the Canadian Optimal Medication Prescribing and Utilization Service (COMPUS) program, within the Canadian Agency for Drugs and Technologies in Health (CADTH), and in collaboration with the Cochrane Effective Practice and Organisation of Care (EPOC) Group and the Cochrane Consumers and Communication Review Group (CC&CRG), have created and continue to update an online database of interventions to promote evidence-based prescribing and medicines use, called Rx for Change is a novel, publicly-accessible database that we initially developed and populated with review-level evidence, and made available online in April 2007. We update it regularly to reflect accumulating and changing evidence and provide decision makers with reliable, up-to-date, evidence-based information in the form of reader-friendly summaries. In the database, we present key findings from systematic reviews that evaluate the effects of interventions directed at professionals, consumers, and organizations in a systematic way. This paper describes the methods for developing and populating the Rx for Change database and highlights key content and the significance of the database for healthcare policy makers, researchers, professionals, and consumers.Rx for Change database is to provide an overall synthesis of the evidence from systematic reviews on the effectiveness of interventions for improving prescribing by healthcare professionals and medicines use by consumers. The methods that we used to populate the database parallels systematic review methodology. We use reliable and valid methods to search and screen the literature, and to appraise and analyse the evidence from relevant systematic reviews. We then present the findings in an online format which allows users to easily access pertinent information related to prescribing and medicines use.Our goal for the Rx for Change database online in a publicly accessible format and has recruited additional funding for this project.In partnership with the Canadian Federal, Provincial, and Territorial Health Ministries, COMPUS identifies and promotes optimal drug therapy and encourages evidence-based information in decision making among healthcare providers and consumers. COMPUS hosts the Rx for Change database, EPOC maintains and updates the evidence from published systematic reviews on professional interventions that impact on the delivery of care, as well as organisational, financial, and regulatory interventions that influence prescribing behaviour. For the purpose of this paper, the methods used to identify and evaluate interventions targeting prescribing will be described.EPOC produces systematic reviews of interventions to improve healthcare delivery and healthcare systems, such as audit and feedback, distribution of educational materials, and decision-support tools using a well-established taxonomy of interventions and methods. In addition, EPOC has conducted overviews of existing Cochrane reviews as well as non-Cochrane systematic reviews to assess and synthesise the evidence in the area of professional behavior change ,5. For tRx for Change database, the CC&CRG is responsible for maintaining and updating the evidence on the effect of consumer-targeted interventions, such as providing consumers with information or education on medicines use, or promoting medicines self-management skills among consumers.The CC&CRG produces systematic reviews of interventions targeted at consumers (patients and their family members or carers) to promote consumer participation in healthcare. The CC&CRG has developed resources and tools to help organise and synthesise the evidence in relation to consumer communication and participation, and members of the group are currently undertaking an overview of systematic reviews of interventions directed at consumers to improve medicines use . For theRx for Change equals four highly trained staff members shared between both Cochrane groups, in addition to supervision from senior research staff.Using the combined expertise of the two Cochrane review groups, we developed the methods used for the synthesis and the presentation of the findings for this database. Human resources required in successfully maintaining With the assistance of an information specialist, we conduct comprehensive regular searches of electronic databases, including MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects (DARE), and the Cochrane Database of Systematic Reviews (CDSR). In addition, we systematically hand-search the CDSR and DARE databases as interventions targeting consumers' use of medicines are not well indexed.http://www.cadth.ca/index.php/en/compus/optimal-ther-resources/interventions/methods). A flow diagram illustrating the methods and procedures for the database can be found in Figure Each year, we identify several thousand potentially eligible citations. Using explicit inclusion criteria, two researchers independently screen titles, abstracts and full text articles for relevance, and compare results. We resolve disagreements through discussion and, when necessary, through consultation with a senior team member  out of the total number of studies for each comparison. We also include any additional review data, such as meta-analyses or effect sizes. We then compile the results from each comparison and present them in a 'Table of Results.' We use standardised decision rules and statements to descriptively report on the general and medicines-specific 'Results' and 'Conclusions' of each review. For example, we use the term 'generally effective' if two-thirds or more of the studies favor the intervention.We organize the reviews of interventions directed to professionals and the delivery of care using the EPOC taxonomy of interventions. This taxonomy groups interventions into five broad categories: interventions targeting healthcare professionals, changing the organization of healthcare, financial interventions, regulatory interventions, and structural changes. Each category includes a number of specific interventions. Examples of interventions targeting professionals include reminders, educational meetings, and audit and feedback. Because the consumer literature on medicines use had not been previously well organised, the CC&CRG developed a taxonomy of consumer directed interventions ,10. ExamWith each update of the database, we combine new evidence with existing evidence and intervention summaries are updated. We display flags that indicate which interventions have been recently updated with new evidence.We present the database in a multilevel approach. In the first level, we provide a list of interventions grouped into five categories: professional, consumer, organisational, financial, and regulatory Figure . In the Rx for Change database on professional behaviour change [We launched the database in April 2007 and have since updated it three times Table . We initr change  and consRx for Change is a well-designed database containing valuable information for researchers, healthcare providers, and policy makers. Since its inception, we have received positive feedback about the database from international users about its value, applicability, and quality. Within a year of its launch, it had accumulated more than 25,000 page views. With increasing awareness of the database and its ongoing updates, we anticipate that this interest will continue to grow. We will continue to disseminate key messages to local and international groups about which interventions are effective, and where gaps in the evidence exist. We will continue to explore methods to disseminate and translate key messages to end users, particularly as new evidence is found and added to the database.Rx for Change database has provided the opportunity for EPOC and CC&CRG to collaborate with organizations that have strong links with healthcare decision makers . This collaboration promotes the use of research evidence and ensures that the data is available to the general public, healthcare professionals, and policy makers.The Rx for Change database to facilitate and improve the processes of accessing, searching, identifying, and using research to inform evidence-based prescribing and medicines use. It provides reliable, up-to-date, evidence for a wide range of users and is organised in an easy-to-browse format. We take the quality of the evidence into consideration to provide useable summaries that are relevant to decision-makers. This database is a first-in-class tool, and we will continue to promote it to ensure that it is utilized to its full potential.We created the BL is currently employed by CADTH. MW, AM, JW, and AS have been or are currently employed by EPOC. JG is the Coordinating Editor of EPOC. RR, NS and DL are currently employed by CC&CRG. SH is the Coordinating Editor of CC&CRG.MW participated in the design, data collection, analysis, coordination of the study, and drafted the manuscript. RR, AM, JW, NS, DL, AS, and SH participated in the design, data collection, analysis, and coordination of the study and contributed to the manuscript. BL participated in the design of the study and provided feedback on the manuscript. JG conceived of the study, participated in its design and coordination and provided feedback on the manuscript. All authors read and approved the final manuscript.


In our consistently doing what we know is right and important for "Medicine and Life", we can express selfesteem and satisfaction after full honest effort with the successful carrying out of the First International Congress "Health – Food – Welfare" which took place at Aro Palace Hotel, Brasov, 15-17 October, 2011, under the patronage of the Romanian Patriarchate, The Romanian Academy, The Ministry of Public Health, The Ministry of Agriculture and Rural Development, The Ministry of Education, Research, Innovation and Sport in collaboration with the International Association of Distribution (A.I.D.A Bruxelles) and EHI Retail Institute. The quality of leadership has been demonstrated by the considerable willingness for cooperation proved by all the stakeholders. That is the reason why we are experiencing a real joy, because, as William Shakespeare said, joy’s soul lies in the doing.Professor Florian Popa, Rector of the "Carol Davila" University of Medicine and Pharmacy, Bucharest and President of the Organizing Committee, and the three Honorary Presidents, Professor Eliot Sorel/George Washington University/USA, Professor Bernd Hallier/Germany, Professor John L. Stanton/University of Philadelphia, USA and other leading professors attending the event to cooperate in the future on the following topics: - a Romanian Competence Center for Global good agricultural practices  and “smartagrifood”; enriching the Eurasian Youth Forum by a "Black Sea/Caspian Sea Area Initiative" to promote together higher education, innovation and the Bologna process; pushing that initiative of cosmopolitan Youth Organizations also via the Astana Economic Forum in Kazakhstan organized among others by the Eurasian Club of Scientists, the Club of Madrid and the G 20. The parties concerned want to use those three activities to create student exchanges by EU-projects like Tempus, Erasmus and Leonardo da Vinci as well as with transatlantic cooperation involving the USAID, USDA and identify the link between higher education, innovation the business community and future employment opportunities and sustainable development in the Eurasia region.As it is already well known, on that occasion a letter of intent had been signed  by


After publication of this work , we noteMr. Meseret and Ms. Fanaye have held supervisions, consultancies and follow up while we are conducting our research. The other authors declare no conflicts of interest.YW: Participated in conception and design of the study, data collection, analysis and interpretations of the findings, reviewed the manuscript; GF: Participated in conception and design of the study, analysis and interpretations of the findings, drafting the manuscript and write up; GY: Supervision of the study, analysis and interpretations of the findings, reviewed the manuscript; DM: Participated in analysis and interpretations of the findings, reviewed the manuscript; MA: supervision of the study, consultation, follow up and reviewed the manuscript; FA: supervision of the study, consultation, follow up and reviewed the manuscript


After publication of this work , we noteThe authors declare that they have no competing interests.CWC, CLC, LKH, HJT and HHC participated in the design of the study and draft the manuscript. SWC, HYS and CWH participated data collection and performed the statistical analysis. CJS conceived of the study. All authors read and approved the final manuscript.


Hospital acquired infections are a major cause of morbidity and mortality and markedly increased health care costs. Critically ill patients who require management in an Intensive Care Unit are particularly susceptible to these infections which are associated with a very high mortality. Selective decontamination of the digestive tract (SDD) may reduce these infections and improve mortality but it has not been widely adopted into practice. We aim to 1. Clarify reasons why clinicians have avoided implementing SDD into clinical practice despite the current best-evidence 2. Describe barriers to SDD implementation and 3. Identify what further evidence is required before full scale clinical implementation would be considered appropriate and feasible.We have developed an international 'multi-lens' approach to investigate SDD from several perspectives. In case studies we will identify accounts of implementation of SDD in practice, in terms of the behaviours performed by the full range of individual clinicians, accounts of how SDD was first introduced into the Unit and specific content that may be used to populate the content of behaviour change techniques to be used in an implementation intervention and procedures to consider in order to deliver an implementation trial. In a 4 round Delphi study we will identify the range of stakeholders' beliefs, views and perceived barriers relating to the use of SDD. We will generate hypotheses about key beliefs about SDD and will inform the feasibility of any future randomised controlled trial. In large-scale nationwide postal questionnaire surveys of the state of current practice we will identify the factors predicting acceptability of an effectiveness or implementation trial using, and informed by, the theoretical domains structure. In semi-structured interviews with active international clinical trialists we will assess the feasibility of a randomised controlled trial and identify challenges and barriers to undertaking research in the field of SDD research.We believe these methods will allow us to determine whether clinical implementation trials or further large effectiveness trials are required before full scale implementation into clinical practice. Each year in the UK 140,000 patients are admitted to an intensive care unit (ICU) and of these almost 60,000 will die within a year of admission. Hospital acquired infections (HAI) are a major clinical problem for modern health services as they are associated with morbidity and mortality as well as high additional health care costs. Critically ill patients are extremely susceptible to HAI and these are associated with a high additional mortality, prolonged hospital stays and a large health care resource utilisation. Between 20 and 50% of ICU patients suffer from such infections and major efforts are being undertaken to improve these outcomes [An intervention that has gained much interest in reducing HAI is selective decontamination of the digestive tract (SDD). SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of intravenous antibiotics -14. The Despite this evidence base, ICU practitioners have not widely adopted this intervention with only 10-15 ICUs (out of 240) reporting that they undertake SDD in the UK ,15. ExisIt seems that until there is high quality evidence demonstrating clinical effectiveness, cost-effectiveness and the ecological impact of SDD in a range of health care systems, this intervention is unlikely to be implemented and thus patients will be denied a potentially life saving therapy. However, despite the clear importance of HAI in critically ill patients, and despite a multi-national appreciation and prioritisation of the importance and urgency of this research topic, it remains unclear why this intervention has not been implemented. Little is known about clinicians' beliefs about the existing evidence base, the perceived benefits and risks of SDD in clinical practice, the factors that influence current practice and likely barriers to implementation. Further, it is also unclear whether there is a requirement for further high level evidence of effectiveness before implementation would become acceptable and what sort of study would be feasible and acceptable to clinicians and trialists. This multi-method study will address these issues in three regions .The overall aim of this study is to identify the perceived risks, benefits and barriers to the use of SDD in critical care units. To achieve this aim, the following objectives are proposed  listed):1. To identify and precisely describe the clinical intervention in units and hospitals that deliver SDD:RQ1: What are the components of the intervention of SDD?• RQ2: How has SDD been implemented and delivered into practice?• 2. To identify the range of beliefs, interpretation and views about the current evidence base relating to the use of SDD in key stakeholder groups:RQ3: What are the views of key stakeholders about the likely positive and negative consequences of implementing SDD in ICUs?• RQ4: What are the views of key stakeholders about the likely barriers to implementing SDD in ICUs?• RQ5: What are the views of key stakeholders of the internal/external validity and adequacy of the existing evidence base for SDD?• 3. To identify current practice and assess the acceptability of further randomised controlled trials in the field of SDD in a wide group of intensive care clinicians and infectious disease clinicians/medical microbiologists:RQ6: What are the current practices and intentions of intensivists and infectious disease clinicians/medical microbiologists about SDD?• RQ7: If there are uncertainties in the evidence base, do these clinicians believe they could be addressed in a clinical trial and what research questions, trial design(s) and interventions would be optimal and what predicts these beliefs?• 4. To assess the feasibility of a proposed effectiveness randomised controlled trial comparing SDD against a control group in ICUs among international intensive care clinical trialists:RQ8: What are the likely challenges in undertaking a large multi-national randomised controlled study of SDD in ICU?• The study will use a 'multi-lens' approach to investigate SDD from several perspectives and in three national regions  to allow greater understanding and international comparisons of the issues that relate to the implementation of this therapy. The investigation will involve four inter-related stages , we will sequentially build a picture of respondents' beliefs and views on SDD. We will further assess the likely factors influencing the acceptability of any future randomised controlled trial comparing SDD against a control group (not including SDD) in ICUs and/or a proposed randomised controlled trial comparing implementation strategies for SDD against a control group in ICUs. Rounds 1 to 3 will be conducted independently within each region, whilst round 4 will be multi-region.There is a broad range of estimates of suitable sizes for a Delphi panel, but smaller sizes (such as 10 per stakeholder group) have been deemed appropriate where panel members have similar training . Four keThe Delphi study report will present (i) the perceived importance of each specific belief about the use of SDD in ICUs; (ii) the acceptability and feasibility of conducting an effectiveness trial; and (iii) the acceptability and feasibility of conducting an implementation trial. In round 4, the data from each regional setting will be presented to all international participants by email. The international comparisons in this round are important, to increase the generalisability of the results and of any future study result, since lack of generalisability may have been a major factor limiting the uptake and implementation of SDD in the past. This round will require that the investigations conducted in each country use a broadly parallel time frame, so that the feedback is presented to all participants with similar time intervals. The full Delphi results will allow us to consider how best to elaborate the key findings from the nationwide survey of the state of current practice, described below.This stage will be conducted in all three regions using large-scale postal questionnaire surveys using existing databases of intensivists and infectious disease clinicians/medical microbiologists in each region. This questionnaire design will be informed by the theoretical domains structure  but onlyParticipants from all three regions as well as European investigators will take part in this stage. We will interview expert national and international clinical trialists in the intensive care field including trialists with experience in SDD to identify challenges and barriers to undertaking research in the field of SDD research. We will seek to recruit 10 participants from across the UK, Europe, Canada and Australia. Semi-structured one-to-one interviews using a topic guide developed from the previous phases as well as from expert experience will be used to study this area. Questions will address potential trial design issues (e.g. need for cluster randomisation), specification of the SDD intervention and of control group care; outcome measurement; recruitment; ethical considerations and other issues raised in the observational and Delphi studies. Data will be transcribed and analysed using content analysis . A full This research will lead to an evidence-based decision about whether to proceed to a clinical trial to evaluate an SDD intervention or an implementation trial . The applicant team/project steering group will make an assessment of whether a trial is necessary, justifiable, acceptable and feasible based on possible patterns of results from the national surveys, for example:1. If intention to implement SDD is low or variable, and predicted by attitude scores and/or scores for specific beliefs about the consequences (benefits and harms) of implementing SDD, it will be judged appropriate to proceed to trial.2. If intention to implement SDD is low or variable and predicted by scores relating to social influence (e.g. pressure from colleagues in other disciplines), this would suggest that an implementation intervention could be effective if delivered by an identified opinion leader, clinical lead or local 'champion' through team meetings. We would proceed to an implementation trial to evaluate such an intervention.3. If intention to implement SDD is low or variable and predicted by beliefs relating to lack of capacity to implement SDD (e.g. resource issues), this would suggest that an implementation intervention could be effective if it focuses on barrier identification and generation of strategies to overcome barriers, known as 'coping planning' , we woul4. If intention to implement SDD is low or variable and predicted (in the multi-level model) at the Unit level, rather than by individual clinicians' views of the evidence, we would design an intervention directed at ICUs rather than individual clinicians. This would be informed by the behavioural analysis of SDD implementation in ICUs where it is currently practised. We would proceed to an implementation trial to evaluate such an intervention.5. By contrast, if intention to implement SDD is high , then the current low level of implementation will be attributable to an 'intention-behaviour gap', suggesting that external barriers prevent clinicians from translating their intentions into action. This pattern of results would suggest that an implementation trial to test strategies for facilitating uptake would be appropriate.Findings about acceptability and feasibility of a clinical trial would also inform the decision about how best to proceed. Specifically:1. If willingness (intention) to participate in a trial is low we will not proceed to a clinical trial.2. If willingness (intention) to participate in a trial is high this will indicate that the trial is sufficiently acceptable to proceed. We will also take into account scores for perceived ease or difficulty of participating.We will also use the consensus data from the Delphi study and the investigation of two ICUs where SDD has been implemented, to decide: (i) behavioural  issues that would need to be addressed in order to mount a trial; (ii) ethical issues relating to informed acceptance of trial entry among eligible patients; (iii) trial design issues including measurement of outcome and process variables. If any one stakeholder group seems to be uniformly of the opinion that there are no design features that would make a trial acceptable, and/or if a third (or more) of the members of two (or more) groups deem any such trial unacceptable, the clinical trial should not be pursued further. Depending on the views expressed about the existing evidence base  we will consider the place of an implementation trial to change clinical practice. If appropriate, the change techniques that would form the components of such a trial will be selected using methods previously reported by members of the research team ,28. The The issue of hospital acquired infections in critically ill patients is a significant issue causing excess morbidity and mortality as well as an excess health care delivery costs. The intervention SDD has the promise to improve these outcomes and is not widely used. This rigorous multi-national study intends to identify the perceived risks, benefits and barriers to the use of SDD in critical care units. This research could lead to a variety of further interventions including a multi-centre effectiveness RCT or implementation study.The authors declare that they have no competing interests.BHC has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper. JF has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper.MKC has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper. LM has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper. IS has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper. JG has participated fully in the design of this study and in the writing this paper and has seen and approved the final version of the paper.BHC is the chief of the Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto and Professor of Anaesthesia at the University of Toronto. JF is an academic Health Psychologist at the University of Aberdeen, Aberdeen, UK. MKC is a clinical trialist and Director of the Health Services Research Unit at the University of Aberdeen, Aberdeen, UK. Lauralyn MacIntyre is a critical care specialist and associate scientist in clinical epidemiology at the Ottawa Health Research Institute, Ottawa, Canada. IS is a Staff Specialist in intensive care at the Nepean Hospital, Penrith, New South Wales, Australia. JMG is a Professor in the Department of Clinical Epidemiology at the Ottawa Health Research Institute, Ottawa, Canada.The SuDDICU groups include-SuDDICU UK study group - Jill Francis, International methods lead, Reader in Health Psychology, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Geoff Bellingan, UK clinical lead, Director, Intensive Care Unit, University College Hospital, London, UK; Marion Campbell, Director, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Brian Cuthbertson, Canadian and International lead, Chief, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Martin Eccles, Professor of Clinical Effectiveness, University of Newcastle, Newcastle, UK; Marie Johnston, Professor of Health Psychology, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK; Graeme MacLennan, Senior Statistician, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Craig Ramsay, Director, Health Care Assessment Programme, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Louise Rose, Assistant Professor of Nursing, University of Toronto, Toronto, Ontario, Canada; Kathy Rowan, Director and Professor, Intensive Care National Audit and Research Committee, London, UK; Rob Shulman, ICU Pharmacist, University College Hospital, London, UK.SuDDICU Canadian study group - Brian Cuthbertson, Canadian and International lead, Chief, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Jill Francis, International methods lead, Reader in Health Psychology, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK; Karen Burns, Clinician Scientist and Attending Physician, St Michaels Hospital, Toronto, Ontario, Canada; Deborah Cook, Canada Research Chair in Critical Care, McMaster University, Hamilton, Ontario, Canada; Peter Dodeck, Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada; Niall Ferguson, Assistant Professor and Attending Physician, University Health Network, Toronto, Ontario, Canada; Richard Hall, Professor of Anesthesiology and Pharmacology Associate Professor of Surgery Dalhousie University and The Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada; Lynn Johnston, Professor of Medicine, Chief of Infectious Diseases, Dalhousie University, Halifax, Nova Scotia, Canada; Salmann Kanji, ICU pharmacist, Critical Care Unit, The Ottawa Hospital, Ottawa, Ontario, Canada; John Marshall, Professor of Surgery, University of Toronto and Attending Surgeon, St Michaels Hospital, Toronto, Ontario, Canada; Lauralyn McIntyre, Clinical Epidemiology, Ottawa Health Research Institute, Ottawa, Canada; John Muscedere, Associate Professor of Medicine, Queen's University, Intensivist Kingston General Hospital, Kingston, Ontario, Canada; Joe Pagliarello, University of Ottawa, Ottawa, Ontario, Canada; Louise Rose, Assistant Professor of Nursing, University of Toronto, Toronto, Ontario, Canada; Fiona Webster, Knowledge Translation Scientist, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Merrick Zwarenstein, Director Centre for Health Services Science, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.SuDDICU Australia and New Zealand Study Group - Ian Seppelt, Australia/New Zealand lead, Nepean Hospital, Penrith, New South Wales, Australia; Simon Finfer, Professor of Intensive Care and Staff Specialist, Royal North Shore Hospital and the George Institute, Sydney, Australia; Jeff Lipman, Professor and Head ICU, Royal Brisbane and Women's Hospital, Brisbane, Australia; John Myburgh, Professor, Intensive Care Unit, St George Hospital Sydney and the George Institute, Sydney, Australia; David Paterson, Professor Infectious Diseases and Microbiology, Royal Brisbane and Women's Hospital, Brisbane, Australia; Brian Cuthbertson, Canadian and International lead, Chief, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Jill Francis, International methods lead, Reader in Health Psychology, Health Services Research Unit, University of Aberdeen, Aberdeen, Scotland, UK;


It is mandatory for sponsors of clinical trials and contract research organizations alike to establish, manage and monitor their quality control and quality assurance systems and their integral standard operating procedures and other quality documents to provide high-quality products and services to fully satisfy customer needs and expectations. Quality control and quality assurance systems together constitute the key quality systems. Quality control and quality assurance are parts of quality management. Quality control is focused on fulfilling quality requirements, whereas quality assurance is focused on providing confidence that quality requirements are fulfilled. The quality systems must be commensurate with the Company business objectives and business model. Top management commitment and its active involvement are critical in order to ensure at all times the adequacy, suitability, effectiveness and efficiency of the quality systems. Effective and efficient quality systems can promote timely registration of drugs by eliminating waste and the need for rework with overall financial and social benefits to the Company. High levels of quality are essential to achieve Company business objectives. Quality, a source of competitive advantage, should remain a hallmark of Company products and services. High quality is not an added value; it is an essential basic requirement. Quality does not only relate solely to the end products and services a Company provides but also relates to the way the Company employees do their job and the work processes they follow to produce products or services. The work processes should be as efficient as possible and continually improving. Company employees constitute the most important resource for improving quality. Each employee in all organizational units is responsible for ensuring that their work processes are efficient and continually improving.Top management should provide the training and an appropriate motivating environment to foster teamwork both within and across organizational units for employees to improve processes.Ultimately, everyone in a Company is responsible for the quality of its products and services.A Company in the role of a sponsor of clinical trials can best achieve its business objectives by establishing and managing robust quality systems with their integral quality documents including standard operating procedures (SOPs).A quality system is defined as the organizational structure, responsibilities, processes, procedures and resources for implementing quality management. Quality management includes those aspects of the overall management function that determine and implement the Company quality policy and quality objectives. Both quality control and quality assurance are parts of quality management.th principle in the International Conference on Harmonization Good Clinical Practice (ICH GCP) guideline clearly states that systems and procedures that assure the quality of every aspect of the  trial should be implemented. The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented (recorded) and reported in compliance with the protocol, Good Clinical Practice (GCP) and the applicable regulatory requirements. Although a sponsor may transfer any or all of its trial-related duties and functions to a contract research organization (CRO), the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor., and local, national, regional and international legal, ethical and regulatory requirements.The quality assurance department under the leadership of a Quality Assurance Manager will ensure the following:Appropriate global and affiliate-specific quality documents  are determined, developed and implemented.Personnel involved in clinical research and development are, and remain, properly qualified and trained for job roles for which they are made responsible. The training will include new staff induction, ongoing quality awareness training including training in applicable SOPs and other quality documents, training for changing roles within and between functional units, and training resulting from an analysis of needs including the results of audits and regulatory inspections, top management reviews and employee appraisals. Further education and additional training needs should be constantly assessed by the Company.All clinical research and development activities are conducted according to Company quality standards, current GxPs, and all applicable local, national, regional and international legal, ethical and regulatory requirements as defined in the quality documents, to meet with Company quality objectives and customer requirements.A system is put in place to track all global and affiliate-specific quality documents and to maintain an up-to-date overall inventory of all historical and effective quality documents.Personnel will have written job descriptions which will clearly define their roles and responsibilities, and the processes and SOPs which they have to follow.A system is put in place to initiate and maintain a personal file on each employee, containing his/her current curriculum vitae, job description, education and training records and personal and professional development plan.An auditing function, independent of the operational units and the quality control system, is created to plan, conduct, and report internal and external audits and to support and monitor their close-out via appropriate corrective actions and preventive actions (CAPA) plan.4 The effA system is put in place to oversee customer audits, regulatory inspections and Company certifications/accreditations as applicable.A system is put in place to a) share audit and regulatory inspection findings and learning with the relevant functional units and top management, b) promote auditing-in-tandem, and cross-pollination of auditors, c) track all internal and external audits, customer audits and regulatory inspections, and d) track status of findings  made during audits and regulatory inspections.Liaison is maintained with functional units, affiliates, and human resources for continued personal and professional development (basic and advanced knowledge-based and skill-based training and retraining) of employees worldwide.Liaison is maintained with and between functional units and affiliates to promote standardization, improve communication, and to enhance efficiency of quality systems through cooperation.All functional units and affiliates are kept up-to-date with various established and emerging local, national, regional and international legal, ethical and regulatory standards.Continual quality improvement initiatives  are identified, implemented and monitored via the Plan–Do–Check–Act (P–D–C–A) cycle.6Persons responsible for the quality assurance system are available in an advisory role to employees worldwide on matters related to the quality systems, regulations in force including GxPs and regulatory compliance.Standardization is defined as an activity that gives rise to solutions for repetitive application to problems in various disciplines including science and it is aimed at achieving the optimum degree of order in a given context. Generally, the activity consists of the process of establishing  and implementing standards. Therefore, standards are the ultimate result of a standardization activity and within the context of quality systems consist of quality documents or documents related to the quality systems.The quality documents consist of Company policies, quality management plan, SOPs, working instructions, conventions, guidelines, forms, templates, logs, tags and labels. They are established by consensus and approved by a nominated body and they provide for common and repeated use, rules, guidelines or characteristics for activities or their results with a view to promote transparency, consistency, reproducibility, interchangeability and to facilitate communication. The hierarchy and types of quality documents relevant to quality systems will depend upon Company business objectives and business model. SOPs are Level 2 quality documents and, along with other relevant quality documents, ensure the effectiveness and efficiency of quality systems.The ICH GCP guideline defines SOPs as “detailed, written instructions to achieve uniformity of the performance of a specific function”. Simply pFor an activity to become the topic of an SOP, it must be either subject to regulations or it must address a task important within quality systems or between quality systems and other functional units. Quality systems related SOPs should generally cover the following topics in order to capture the core quality control and quality assurance activities and processes:Definition, format, content, compilation, indexing, review, approval, update, distribution and archiving of quality documents;Definition, format, content, review, approval, update, distribution and archiving of quality management plan;Definition of and activities related to quality control of clinical trials and compilation of trial-specific quality control plan;Initiation and maintenance of personnel files including format and content of curriculum vitae, job description, training records and personal and professional development plan;Top management reviews of quality systems and issuance of management review reports;Selection and management of contract auditors;Format, content, compilation, review, approval, update, distribution and archiving of audit program;Format, content, compilation, review, approval, update, distribution and archiving of audit plan;Planning, conduct, reporting and close-out of risk-based internal and external audits;Planning, conduct, reporting and close-out of specific audits of sites, processes, systems and documents: sponsor site, third party  site, investigator site, quality management system including SOP management, education and training and auditing, document management system including archives, data management system including information technology support, serious adverse events management system, pharmacovigilance system, medical dictionary management system, and regulatory submission documents ;Planning, conduct, reporting and close-out of for cause/directed audits;Hosting of customer audits;Preparation of sites for regulatory inspections;Coordination and management of regulatory inspections;Format, content, compilation, review, approval, update, distribution and archiving of CAPA plan, and assessment of its effectiveness;Change control to ensure that changes and the current status of quality systems related components including documents are identified; andRoles and responsibilities of quality assurance in handling of scientific misconduct/fraud.The importance of properly established and managed quality control and quality assurance systems with their integral well-written SOPs and other quality documents for the achievement of Company business objectives cannot be ignored. They serve as a passport to success by assisting the Company to achieve high-quality processes, procedures, systems, and people, with eventual high-quality products and services and enhancement of the following:Customer satisfaction, and therefore, customer loyalty and repeat business and referral;Timely registration of drugs by eliminating waste and the need for rework;Operational results such as revenue, profitability, market share and export opportunities;Alignment of processes with achievement of better results;Understanding and motivation of employees toward the Company quality policy and business objectives, as well as participation in continual quality improvement initiatives; andConfidence of interested parties in the effectiveness and efficiency of the Company as demonstrated by the financial and social gains from Company performance and reputation.


Originals were translated into popular reproductions on matchboxes, postcards, calendars, and home designs, all illustrated with a richness reminiscent of the Byzantine icons he loved and collected. Accessible and dynamic, they became part of the vernacular, their figures harmoniously integrated with the surroundings in complex linear compositions. Curves, spirals, and intricate ornamentation spilled over into architectural and folk designs and dominated graphic art."We can't allow a split… ranking one art above the others," wrote artist Henry van de Velde in 1895, articulating a doctrine of art nouveau: art should affect the lives of all people, should enter their homes and influence their furnishings, uniting beauty and utility  to glassware (Louis Comfort Tiffany in New York).For Mucha the astonishing success of his popular designs was only a prelude to what he considered his best work, The Slav Epic, a monumental painting inspired by his devotion to the Czech people. He died of pneumonia before the work was finished. Reaction to the painting was mixed, and his fame, particularly among his compatriots, diminished, to be revived again during the 1960s and remain strong to this day.Zodiac, on this month's cover, shows why Mucha's work was instantly popular. The image exudes comfortable familiarity even as it invites contemplation. The human figure and its surroundings, harmonious and integrated, are evocative of nature. Floral and celestial elements are arranged symmetrically around a portrait, the focus of the intricate composition. Gaze and posture show directness, innate confidence, a sense of self. Filled with energy and movement, she is the dominant star in the celestial sphere. And "flowering" into the complex botanical frame, she captivates with poise and modesty. An exotic gypsy queen, she holds the mysteries of the zodiac, the flow of time, the riddles of nature, the fortunes of the world, deriving her power and magnetism from the symbols surrounding her, in perfect harmony and balance with the content of the universe.A common motif in Mucha's work, the zodiac alludes to the birth of life and tries to identify and define it, predict its course, and control its outcome. Derived from the artist's faith in the spiritual aspect of art and the power of tradition as source of inspiration, it does what art nouveau sought to do, elevate folk elements to fine art accessible to everyone.The desire near the end of the 19th century to beautify and advance the world culturally as it was advancing and evolving scientifically is understandable. Social purpose in art, which graces the mundane for the common people, is no different from social purpose in medicine, which improves and extends their lives. Public service for the greater good is like fine art for the masses. Mucha's Zodiac seems a fitting astrologic birthday card, as the Centers for Disease Control and Prevention celebrates 60 years of identifying, describing, explaining, and preventing unknown elements for the benefit of humanity.


Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and controlling the release of drugs and, therefore, improving therapies, nanoparticles have been the subject of research and patent applications in the pharmaceutical field. According to the Organization for Economic Co-operation and Development (OCDE), patent data can be used as a source of information in order to measure science and technology activities. Thereby, this paper presents an analysis based on patent documents related to nanotechnology in the pharmaceutical sector. As a result, the analysis of patents demonstrate primarily that nanobiotechnology attracts high levels of R&D investments, including nanoparticle-based chemotherapeutic agents/drugs, monoclonal antibody nanoparticle complexes and their role in drug delivery or contrast agents with non-toxic effects. The global nanotechnology industry was valuing $300 billion (bn) in 2011 and is expected to be worth $1.6 trillion at the end of 2013 and $35,000 bn by 2041. Nanotechnology’s fastest growing sector—nanobiotechnology—is poised for a rapid growth, especially in the field of targeted drug delivery therapies in the oncology sector. The nanobiotechnology market will reach $6 bn by 2017 [There is a myriad of new opportunities in terms of advances in medical science and the treatment of diseases affecting humans. Applications of nanotechnology in medicine and physiology are represented by material and equipment designed to interact with the body on a sub-cellular (or molecular) scale, with a high level of specificity . In moreIt has become increasingly necessary to understand the effects and level of application of biological systems together with nanostructures in the development of research linked with the areas of medicine and health.The applications of nanobiotechnology allow the creation of material and equipment at the same level as the live organisms, bacteria and even plants. The ability to work on this scale not only provides more control of the biological world, but also leads to empowerment from the use of extraordinary inventions that nature itself has produced after thousands of millions of years of evolution .Not only biomedicines and conventional drugs, such as those used for chemotherapy, but also short strands of interference RNA (gene silencers) are frequently incorporated in vehicles, such as polymers or lipidoid molecules, for the purpose of directing a preferential trajectory in the human organism .The utilization of nanoparticles allows the liberation of a therapeutic agent in a pre-defined location in the organism, the treatment of a huge number of diseases, including diabetes, Alzheimer’s disease, several inflammatory infections, such as arthritis and rheumatism and asthma, as well as cancer.A plethora of other potential benefits of nanobiotechnology in the area of health can be cited, including:✓The new techniques involving molecular images, which allow us to understand the physiological processes of the human body on the nanoscale, thus leading to the development of methods to diagnose and treat diseases more accurately and sensitively. One example in particular is superparamagnetic nanoparticles using proteins for the molecular imaging of cancer;✓ex vivo tests;The new qualitative tools of analysis that will allow for a better understanding of the working of cells at a molecular level and, particularly, the cells related to diseases. The union of proteomic and metabolomic genes into nanobiotechnology will allow for the development of more efficient and specific medicines for each type of disease. Another benefit will be the development of more sensitive and specific ✓Nanosensors and nanorobots, which when introduced into the body orally or intravenously, can identify and destroy cancerous cells or those infected by a virus, as well as regenerate damaged issue. These nanorobots can also be used to monitor vital functions  in patients that require constant medical care.The use of bibliometric indicators can be an efficient method to analyze research activities. Patent documents are the most important source of technological information, as they contain 71% of all the technology developed around the world, as well as the advantage of being globally standardized. Statistics on patents have been used as indicators of the results of invention-related activities . This paThe aim of this paper is to analyze the main trends of patenting related to nanotechnology applied to the pharmaceutical sector.For the recovery of patent documents, the database selected was the Derwent Innovations Index (DII), with the coverage of more than 11 million patent documents filed, published—and eventually granted—from 1963, in more than 40 countries. This database contains patent applications in the areas of chemistry, electricity and electronics and engineering, and its main advantage is the fact that all the patent documents in it are indexed, and their summaries were drawn up by specialists in the area. As such, the summaries are full of keywords and available in English, together with their titles, independent to the country the patent application was filed in and published, which facilitates the recovery of the documents using defined search strategies.The main reasons for the choice of this patent database were:✓®[The possibility of exporting the patent documents recovered in the search, in their entirety, using software designed to work with this type of information, such as, for example, the commercial software, Vantage Point®, used in✓The availability of Manual Codes, a classification attributed in the database to all the patent documents indexed in it. This classification also has a hierarchical structure, such as the International Classification of Patents (IPC) , althougFor the search of patent documents related to nanotechnology applied to the pharmaceutical sector, the classifications in the Manual Codes were selected as listed below , which aRemoving the patent documents that were in more than one of the nine series in For the purposes of restricting the series of patent documents obtained, focusing on the special issue “Bioactive Nanoparticle 2012” in the section “Biochemistry, Molecular Biology and Biophysics” of this journal, searches were made in the “abstract” field of the documents, using the keywords listed in The keywords used define different areas of nanobiotechnology, and some are significantly intersected. Of the 17 documents related to the toxicity of nanomaterials, 11 are also contained in the area of nanoparticle toxicity, and the others have a similar focus on this group. In addition, in the areas of nanoparticle cell interaction and nanoparticle protein interactions, the documents of the top-ranked entities filing patent applications are also largely included in the area of nanoparticles used for drug delivery.Given this, the main focal points and the analysis of the main patent applications filed fall into the following four areas:✓Toxicity of nanoparticle;✓Nano-imaging agent;✓Nanoparticle for drug delivery;✓Cancer-targeting nanoparticle.The analysis was based on the top applicants of patents in the four focal points cited above. Based on The trends of the main applicants for each area in A total of 347 patent applications were filed under this subject around the world in the last ten years and involved 268 different applicants, either in partnerships or not, of which 216 have single applications. This means only one patent application per applicant.The leader in patent applications filed in this field is General Electric, with 10 patents, followed by the Massachusetts Institute of Technology (MIT), with eight patents. Four other entities filed seven patents each: the Irish company; Abraxis Bioscience LLC (a Celgene Corporation subsidiary), the French Institute, Centre National de La Recherche Scientifique (CNRS), the Irish Elan Pharma International, Ltd and the University of California, in the United States. Only the patent applications filed by the main institutions were considered in this analysis.As cited, General Electric (GE) is the company holding the most patent documents under the subject of toxicity and nanoparticles. There are no partnerships in the documents analyzed, and the focus of the use of nanoparticles is related to compositions. The composition for a magnetic resonance imaging contrast agent useful for obtaining a magnetic resonance image (MRI) of a tissue or organ of an animal or human that minimizes toxicity or other discomfort to patients is the main issue in US2006018835 . Along tIn second place under this topic is MIT, with eight patents, of which two were filed in partnerships. The patent application filed in partnership with Brigham & Women’s Hospital Inc. relates to the new composition comprising a nanoparticle and a biocompatible polymer. The composition is useful in delivering drugs for treating pathologic conditions, e.g., cancer. The composition reduces the amount of a drug present in tissues of the body that are not targeted . The parThe seven patent applications identified and attributable to Abraxis Bioscience are mainly based on administering compositions comprising nanoparticles , useful for treating pulmonary hypertension, lung cancer, esophagus cancer and that reduce side effects and are non-toxic –23.The Irish company, Elan Pharma, which focuses on the area of biotechnology, has seven patent applications filed under the same topic, with only one in partnership with Alkermes Pharma Ireland Ltd. The patents filed by this company concern, for example, nanoparticulate composition comprising a drug that exhibits chemical stability under environmental conditions, such as prolonged storage periods, and does not require the addition of potentially toxic solvents . AnotherBeing a research institute, the Centre National de La Recherche Scientifique (CNRS) has partners in six of the seven patent documents selected. Most of these partners are universities or other research centers, such as Université Paris Sud, Lyon University, the University of Versailles Saint Quentin En Yveline, University Fourier Joseph, the University of Strasbourg, the Macromolecular Chemical ASCR Institute, Montpellier University, Rennes University and Institute National Sante & Recherche Medicale. Only one company was identified as a CNRS partner, Ethypharm SA. The patent documents filed by CNRS with its partners, Université Paris Sud and Ethypharm, are related to, for example, biodegradable polymeric nanoparticle composite useful for the manufacturing of a drug used to treat cancer, bacterial or viral systemic infections and the encapsulation and vectorization of molecules having a therapeutic effect. The polymer exhibits less instability and toxicity on non-cancerous cells .The patent documents filed by the University of California in this area did not include any partners and are related to determining the toxic potential of nanomaterials (NMs) and comprises providing a culture of cells, adding a quantity of NMs and performing assays for oxidative stress on the cells. The invention provides test procedures to ensure the safe manufacturing and use of NMs . AnotherConcerning the patent documents related to the application of nanotechnology in the sector of agents of molecular imagery, 327 patent applications were filed between 2002 and 2012. Of particular note in this universe is the total of 241 patent applications made, either in partnership or not, of which 178 were made by a single entity, and that four entities filed more than five patent applications.The leader in this field is General Electric, with 20 patents, followed by the University of California, with nine patents, Konink Philips Electronics, with eight, and the University of Texas System, with six.in vivo magnetic resonance imaging measurements and comprises carbon-13-enriched fullerene or carbon nanotube molecules [General Electric (GE) is the company with the most patent documents filed in the field of nanotechnology related to image agents. Of the 20 documents analyzed, only two were made with partners, one with Oxford University (USA) and another with the company, Hammersmith Imanet Ltd. In the patent documents filed by GE alone, the technological focus is mainly related to contrast agents used in magnetic resonance, as in patent application, US2005260137, related to a contrast agent useful for magnetic resonance imaging that comprises several nanoparticles and provides enhanced relaxation, high signal-to-noise ratios and targeting abilities . The conolecules . Patent olecules .in vivo imaging and therapy that detects diseased cells by MRI, PET or deep tissue near-infrared (NIR) imaging. Patent application, WO2010096828, is related to a layered nanoparticle comprising a biocompatible layer useful for manufacturing multi-model imaging reagent for imaging living tissue and for treating cancer [The University of California, second in the ranking in this field, filed nine patent applications, all in partnerships. The abstract supporting patent application, US2006003464, presents a nano-crystal that emits light when energized and an affinity molecule linked to the semiconductor useful for determining the presence of detectable substance in a biological material and for imaging the same sample by both light and electron microscopy . AnotherKonink Phillips Electronics filed eight patents in the area of nanotechnology associated with image agents, and only one was made in partnership with FEI Corp. As examples, we can cite WO2005070473, which refers to a contrast agent, useful for manufacturing an ultrasound contrast agent comprised of solid metal nanoparticles having an acoustic impedance useful in diagnosing ultrasound contrast imaging and imaging an isolated tissue sample or organ; and patent application, WO2006054240, is related to a contrast agent for medical diagnostic and imaging, comprising metal nanoparticles encapsulated in and/or attached to non-proteinaceous biocompatible or biodegradable matrix particles ,36.in vitro diagnosing of cancer in a subject [The University of Texas System filed six patents, with partners in only two, one with the University of Rice William Marsh and the other with the University of Ohio States. Their focus on nanotechnology is mainly linked to imaging agents. For example, patent application, US2008124281, relates to a magnetic resonance imaging contrast agent for molecular imaging applications in cancer . The MRI subject .A total of 294 patents were filed in this field by 224 institutions, of which 166 were single entities. Of this last group, approximately 60% were made by universities and/or research centers, suggesting that although still an emerging technology, significant advances have been made over the past few years, with applications in several different areas and that already account for some of the applied research and innovations in the biomedical area. Most of these patents were filed by American institutions, with around 80 of the applications. This data can be corroborated when looking at the timing of the patent filings, excluding those still not published, due to the statutory 12-month grace period for a public disclosure.The National University of Tsing Hua, in Taiwan, was the leader in terms of patent applications in this field; with 12 filings, of which 11 were made in partnership with GP Medical Inc. Nine of these patent applications involved a composition of nanoparticles, which uses a shell of chitosan, a non-toxic and soft-tissue compatible molecule that enhances diffusion across mucosal epithelia, loaded with the drug to be administered. It is known that hydrophilic medicines, such as peptides and proteins, do not diffuse easily to the blood flow through the intestinal epithelium, and the acid environment in the stomach can degrade these medicines when administered orally, which emphasizes the therapeutic relevance of these new pharmaceutical compositions .In second place was the University of California, with seven patent applications. Patent application, WO2008066965, highlights a manufacturing product that provides biocompatible nanostructures with an increased surface area for enhanced cell and bone growth used in a drug delivery orthopedic device or dental implant, while WO2011143201 presents a new multi-drug conjugate with the main advantage that it controls the molar ratio among multiple drugs and their concentration taken up by the same target cell, optimizing combination therapy regimes ,41.The Massachusetts Institute of Technology is next, with a total of six applications, of which two were made in partnership with Brigham & Women’s Hospital Inc. and one with the Children’s Hospital in Boston. Of note among these, WO2008011561, is an application protection for new end-modified poly (beta-amino esters) polymers useful for delivering polynucleotides, contrast agents, RNAi and siRNA for delivering nucleic acids in gene therapy, which have the great advantage that the polymers exhibit improved chemical properties, such as degradation time and ionizability . AnotherA total of 245 patent documents were retrieved in this category. Most of the applications were based on a pharmaceutical composition containing nanoparticles for treatment, not for a specific type of tumor, but several types, including prostate, breast, ovarian, lung, colon, bladder, lymph and melanoma.The main patent filer is the Massachusetts Institute of Technology, with a total of 11, of which six were made in partnership with Brigham & Women’s Hospital, one with Bind Biosciences Inc., another with Cornell University, one with Northwestern University and, finally, one with the Children’s Hospital in Boston.In general terms, the patent applications are for new methods and compositions for delivering drugs for cancer or for treating cancer. Patent application, WO2008124639, for example, relates to a controlled-release system comprising target-specific stealth nanoparticles useful for target-specific treatment of a disease and the delivery of a therapeutic agent . It is wThe possible uses cited in the abstracts include not only the treatment of tumors, but also various other diseases. The already cited application, WO2008124639, includes the treatment of atherosclerosis and restenosis, for example . On the in vivo imaging and therapy that detects diseased cells with greater sensitivity than is possible with existing technologies and targets molecules that localize normal or diseased cells initiating the apoptosis of diseased cells [The University of California is in second place in this field, with a total of nine patents. Approximately 90% of patent applications are related to the treatment of several types of tumors, using some extremely original ideas. US patent, 2006019900, illustrates the utilization of a protein in cellular adhesion, alpha-4-beta-1 integrin, for treating cancer and an inflammatory or autoimmune disease. The big advantage is that the ligand displays high binding affinity, specificity and stability and is more resistant to cleavage or degradation from proteases found in plasma, gastrointestinal tract and tumor cells . The apped cells .To illustrate the existing partnerships between entities, we drew up the following chart  for the As can be seen in In the toxicity and nanoparticles area, the partners of MIT are Brigham & Women’s Hospital Inc. and the University of Northwestern. In nano-imaging agents, the patents were filed by MIT with General Hospital Corporation, University of Cornell and Brigham & Women’s Hospital Inc. In nanoparticles for drug delivery, MIT has patents with Brigham & Women’s Hospital Inc. and Children Hospital Boston, and in cancer-targeting nanoparticles, the partners of MIT are the University of Northwestern, the University of Cornell, Children Hospital Boston, Harvard College, the Immune Disease Institute and Brigham & Women’s Hospital Inc. Furthermore, Brigham & Women’s Hospital Inc. has partnerships with the Immune Disease Institute and Harvard College in this area. It is remarkable that the partnership between Harvard College and the Immune Disease Institute is the strongest one, as can be seen by the intensity of the line connecting the two institutions in The rising development of nanotechnology in the area of biomedicine can be attributed to the technological advantages, including better distribution profiles of medicines in the organism and directing them to specific organs, which reduces the necessary doses and, consequently, the toxicity and adverse effects. In addition, the possibility of the controlled release of therapeutic agents makes therapy far more efficient and convenient for users, with better patient adhesion to the treatment, particularly those with chronic diseases that require continued administration and repeated doses of medicines.Also, the toxicity of the nanoparticles and nanomaterial in general is a question that has had an impact in terms of the development of innovations, mainly due to the scarcity of information related to the potential risks to human and environmental health. However, an analysis of the patents that combine toxicity with nanotechnology appears to justify the use of nanoparticles, generally encapsulated as drug delivery or contrast agents, with a non-toxic effect.One of the main challenges faced in the development and use of medicines for cancer is to ensure that they are concentrated primarily in the affected organs, at selected levels of toxicity in cancerous cells, thus preserving the healthy ones. Due to their reduced size, nanoparticles tend to accumulate in tumors, with less effect on other parts of the organism, which increases the therapeutic efficacy and reduces the main adverse effects caused by chemotherapy, such as vomiting, diarrhea and hair loss.Dynamic, proactive and socially responsible research will drive nanomedicine as it plays an increasingly integral and transformative role in medicine and public health in the 21st century.


There are post-mortem investigations of serious scoliosis with a LILF of the DM. In early research, it was considered to be a secondary phenomenon, as a consequence of the vertebra’s edges pressure in the vertebral channel, towards the dura mater..First, to prove that the LILF of the DM is not the secondary phenomenon. On the contrary, the LILF of the DM, like a hooked bowstring, causes a serious idiopathic scoliosis. Second, to create an MRI test, so any competent scoliosis expert, could see an initial LILF of the DM, and predict early a dangerous development of scoliosis.We used the Cheneau - Abbott type braces with the non-magnetic parts, and the side position of patient for MRI-test. We investigated the form, and the locations, of the spinal cord in the corrected position of the scoliosis spine.We find that the starting scoliosis has LILF of DM in several cases. These are serious scoliosis in future.The MRI test, for a LILF of the DM, can help to make a forecast of the future development of scoliosis. We can make the early scoliosis treatment easy, by separation of the LILF of the DM, like Edville Gerhardt Abbott (1913), by overcorrection brace, or maybe by micro invasive surgical releasing in the future.