Dear Editor,Since 1979 when revolution happened in Iran, this country started facing some embargos and limitations form the US side that step by step became expanded . The UniNevertheless there are disagreement on “What is the extent of the impact of sanctions?” there is no doubt that above-mentioned embargoes could impact on political relations, economy, oil price, humanities and foreign exposure and transactions of Iran. Although pharmaceuticals and medical equipment did not stand under international embargos, the country has faced reduction of medicines for treatment of several diseases such as cancer, cardiovascular and respiratory illnesses, thalassemia and multiple sclerosis (MS). A principle reason is inability of Iran to pay via international transferring systems due to sanctions . In a reUnfortunately, alongside the above mentioned embargos, there are hidden aspects of such thinking, which directly or indirectly affect the ordinary scientists, academics, researchers and also students inside or outside of the country. For instance, very recently the famous publisher Elsevier inquired its American editors and reviewers not to exert the manuscripts, in which there are any Iranian co-authors employing in the government of Iran . This waAs recently published in BMJ, several papers have been refused by journals in the US and Australia e.g. American Journal of Cardiology (published by Elsevier), the Journal of Ocular Pharmacology and Therapeutics (published in the US by Marie Ann Liebert), and the Australian journal Ophthalmic Epidemiology) in the recent months because of the sanctions. On the other hand, Dove Medical Press  turned down a paper saying that “international sanctions currently in place against Iran mean that Dove Medical Press is no longer able to process manuscripts received from Iranian authors” .Together with all the mentioned consequences, academic people of the country are facing other side effects of such sanctions during the past years. For example, they have many problems with money transaction in order to do scientific activities for example payment of publication fees, society subscription fee, or registration fee in international congresses, etc. This is due to the reason that Iran is deprived to go through the international payment systems. Boring process of getting visa for participating in academic events, international conferences and symposiums are just the instance examples of the terrible concerns for Iranian faculties and students. The students suffer problems in getting visa from the US and those who study abroad cannot receive their financial supports from their parents inside the country. These all have made extra burden to Iranian scientists and students. Traditionally, the US has been one of the goal countries to which talented Iranian students and scientists are interested to travel to achieve higher scientific positions. At the moment, the challenges of travel between these two countries for scientific collaboration are very daunting. Nonetheless, it seems that there is a silent and progressive collaboration mutually between Iranian and western  researchers and faculty members in case of international cooperation on science and technology. The science of “Toxicology” is one of the examples that is growing fast to be global, in which there are diverse countries found in SCImago for their scientific production in toxicology. Surprisingly among 10 top countries Iran from Middle East and USA from Northern America are listed while toxicology societies play a considerable role in such cooperation in presence of all embargos .Although there was a big achievement in science and technology for Iran during the past years , the ratUnfortunately, growing tensions over Iran’s nuclear program consequently affected Iranian academics and students who were going to get visa to visit abroad. It is reported that “at least half a dozen Iranian graduate students in engineering who were slated to attend universities such as Michigan State, Southern Illinois, South Carolina, Pittsburgh and Northwestern this year couldn’t come because the U.S. rejected their visa applications under the same espionage clause”, Bloomberg News has found .Taking together, as the scientist, we believe the sanctions if imposed against any country even intended or unintended hurt the scientists and the basis of science and thus it is an unfair action. Alongside diverse influences of embargoes on sanctioned countries, high graduated people face various problems which can provide many tribulations for them leading to stop or suppress their scientific works, researches and achievements. This might easily interfere in scientific findings not to be spread and published on time or at all leading to delay in reaching to important and key data.


Croatian Medical Journal (CMJ) appointed Research Integrity Editor in 2001, which paved the way for the introduction of computer detection of plagiarism  and the introduction of CrossCheck (http://www.crossref.org/crosscheck/index.html), a unique web-service for detecting plagiarism in scientific publications, marked the beginning of a new era at the CMJ.The story began when Mladen Petrovečki and Lidija Bilić-Zulle, members of the students ,5. Togetstudents ,6. The sBritish Medical Journal  containing plagiarized parts (8% true plagiarism and 3% self-plagiarism)  and manual verification of manuscripts suspected of having been plagiarized (more than 10% text similarity). The criteria for plagiarism were set according to the prior investigations carried out by Bilić-Zulle et al ,5 and Se Journal . Manual giarism) .CrossCheck is an excellent service for detecting plagiarism, which detected almost all plagiarized manuscripts in our study. eTBLAST was less informative, possibly because at the time of the investigation it only had the ability to compare the text with abstracts from the Medline database .If a suspected case of copy/paste activity was found, the investigator wrote a plagiarism report to the Editorial Board to assist in deciding on the manuscript’s status. Editors mostly accepted the suggestions and in case of disagreement, the final decision lay with the Research Integrity Editor. Cases of blatant plagiarism were easy to deal with because of text similarity in all sections of the manuscript, while those with less text similarity were sometimes more complicated and COPE’s flowcharts were not sufficient to conclude whether the manuscript was plagiarized.Special attention was paid to plagiarism in the Results section. Also, there was zero tolerance for plagiarism in the Discussion section. When manuscripts contained plagiarism in the Materials and Methods section or when the original article was not cited in follow-up investigations, accidentally or by ignorance, authors were given an opportunity to rewrite the text and publish their investigation. These examples once again show that it is of genuine importance for editors to become educators, ie, to teach authors about standards in publishing and research through continuing education .We believe that the main reasons for plagiarizing were unawareness of research integrity policies, poor English proficiency, attitudes toward plagiarism, and cultural values ,11-13. IPlagiarism is not easy to define ; there aCMJ was the first scientific journal in Croatia to begin checking all the submitted manuscripts for plagiarism (2009) and, to the best of my knowledge, together with the Chinese Journal of Zhejiang University Science, the only journal in the world that has systematically collected data on plagiarism in the submitted manuscripts. Furthermore, the CMJ is the first medical journal to publish the standard operating procedure for scanning submitted manuscripts (study protocol), as part of the journal’s “striving for excellence” policy (The ” policy ,18.Plagiarism detection software enables systematic detection and prevention of plagiarism, leading to fewer retractions. The results of our study were published  and we e


In the article “Screening Performance of Diabetes Risk Scores Among Asians and Whites in Rural Kerala, India,” an omission occurred in the Acknowledgments section. That section should read:“The research had no external funding. We thank all the study participants. Thirunavukkarasu Sathish is supported by the ASCEND Program funded by the Fogarty International Center, National Institutes of Health, under award no. D43TW008332. This article was presented as a poster display in the World Diabetes Congress organized by the International Diabetes Federation December 4–8, 2011, in Dubai, United Arab Emirates.”http://www.cdc.gov/pcd/issues/2013/12_0131.htm. We regret any confusion or inconvenience this error may have caused.The correction was made to our website on July 11, 2013, and appears online at


Journal of Community Hospital Internal Medicine Perspectives (JCHIMP), www.JCHIMP.org. It could be looked at as the journal's first birthday. It has the largest number of published manuscripts to date. The theme of this issue is case reports; it includes a perspective on case reports as well as numerous interesting cases that have been submitted by residents and faculty.This is the fourth quarterly publication of the Medical Education Online, we first called for papers 1 year ago in January 2011. Initially, we limited our manuscript call to original research, perspective pieces, case reports, medical education innovations, and an electrocardiogram column. In this, issue number 4, we have expanded to include brief reports and medical imaging. In our next issue, we expect to inaugurate the first in our History of Medicine series.Publishing case reports is part of the journal's mission. JCHIMP was organized in 2010 to respond to various needs expressed in the internal medicine educational community, including the need for a journal with community hospital orientation that would be a scholarly vehicle for residents and faculty. After contracting with the publisher Co-Action Publishing based in Stockholm, Sweden, in 2010 and developing a mentoring relationship with David Solomon, editor of At the end of the first year, the journal is thriving. The journal has a 15-member editorial board, an editor, and managing and assistant managing editors. Except for some administrative assistance and the actual publishing costs, everything is done voluntarily. Our financing has three sources: a $350 publication fee for non-invited articles, donations from our readership (fully tax deductible), and generous financial support from MedStar Health System based in Columbia, Maryland, and the Union Memorial Hospital Department of Medicine in Baltimore.If you have not read the journal, please sign up. It is a remarkable technology. Depending on the timing, it is not difficult to publish in final form articles that were submitted not more than 3 months prior. This has happened on a number of occasions so far this year.www.CHERNINFO.net). We foresee the journal as serving as an enduring publishing arm of CHERN.We believe that the future of JCHIMP lies in its constituency in the community hospital network, that is, the Association of Program Directors and the voluntary subgroup, Community Hospital Education and Research Network (We are very pleased with our peer reviewers. In the first four issues, 79 volunteers have completed reviews and are listed in What we have accomplished to date? More than 2,500 ‘unique individuals’ have read the journal from 88 countries as of December 1, 2011. We have established our manuscript and article style – brief, succinct, and with a teaching message. Trainees are included at all levels in the organization, including readers and reviewers.Where do we go from here? Our spring issue will have a diabetes treatment theme and will also include the first in our History of Medicine series. We plan to apply for ‘indexing,’ once we have the requisite number of articles published. We continue to recruit more reviewers and get them to engage in the program. As we become more widely known, we hope to have a broader scope; although, 88 countries is a good start.David Widlus (Marc Mugmon (This issue contains 11 manuscripts, including this one  and a ped Widlus . Two eled Widlus , and an c Mugmon . A perspc Mugmon . Four cac Mugmon , Moxifloc Mugmon , fatal mc Mugmon , and ‘myc Mugmon . The latWe will continue to publish quarterly. There is no limit to the number of manuscripts in each issue in our paperless journal. No limit except for the capacity of our volunteers. It is a lot of work, but it is also a lot of fun. We believe that what we are doing has an educational impact at many levels. I must confess that I love working with the students, residents, and faculty and hope that we are making a difference, raising their scholarly horizons. We believe that we are having an educational impact. We try to do it with a trace of wit because we believe that humor makes teaching fun.Robert P. Ferguson, MDEditor


The Lancet, The New England Journal of Medicine, and The British Medical Journal, reflecting developments in science and educating physicians and eventually changing clinical practice worldwide. Multiple functions assigned to scholarly journals raise the issues of trustworthiness and quality of the publications. The latter is of particular importance in view of recent trends in information flow, digitalization, and acceleration of the publishing process, which may increase the rate of errors and mistakes.The current pace of developments in virtually every aspect of our life and scientific innovations pose ever increasing challenges in ensuring the highest possible quality of publications, satisfying the needs of both publishers and readers. Scholarly journals are essential tools for communication between experts and for advancement of research and practice in various fields of science . By commsanctum sanctorum for any journal. Journals supported by learned societies, academic institutions, and leading publishers are in a privileged position, as they can afford to support the maintenance of editorial offices and secretarial services, prerequisites of a successful journal  submit good manuscripts plus invited editorial commentaries. No less important are the editors’ efforts to improve editorial policy, the quality of peer review, and the validity of publications. Editorial board meetings should be organized regularly to discuss such matters. Most top general medical journals such as The criteria for editors’ qualifications vary between general and specialized journals and from country to country, but, undoubtedly, most journals would benefit from recruiting experts familiar with international standards of science writing and editing, members of learned societies such as the Council of Science Editors (CSE), the World Association of Medical Editors (WAME), the European Association of Science Editors (EASE), and those accredited as professional editors . In addition, it is becoming increasingly important to adhere to the principles of ethical publishing outlined in the guidelines of the Committee on Publication Ethics (COPE), and most journals and individuals involved in science editing are encouraged to join COPE. Many leading publishers pay a group subscription to COPE for all their journals, eg, Elsevier, Wiley-Blackwell, and Informa Healthcare.For English language journals, particularly those published in non-Anglophone countries, language editors with qualifications from leading linguistic institutions in Oxford, Cambridge and elsewhere, membership in relevant associations , and skills in science editing are valuable assets. Language editing, correcting grammar and style of the titles, abstracts and key words can be the first step toward enhancing the quality of publications and improving the influence of the papers. Some high-impact journals even employ title and abstract editors . EditorsDepending on the rate of manuscript submissions and their quality, journal editors may choose to rely on either internal or external peer-review or both. Internal processing of the submissions is primarily aimed at filtering out manuscripts with irrelevant scope, incomprehensible language and narrative, and apparent errors in scientific design and methodology. Rapid internal review is a good service to the authors and, in case of rejections, is a tool for saving editors’ and external reviewers’ time and efforts . For jouHighly selective databases such as the Science Citation Index and MedLine/PubMed place a great importance on the originality of the journals applying for indexing. This implies a unique journal title, specific scope of interest, original content of the published articles, and defined professional and geographical representation. Additional value is given by content of international importance and of interest to scientists around the world, even if publications are based on national/local studies.Proceedings of the National Academy of Sciences of the United States of America, Science, and Nature. Exemplary are titles of the journals belonging to professional societies in certain regions: Journal of the American College of Cardiology, Journal of the Royal College of Physicians of Edinburgh, etc. Editors expecting the majority of submissions from their academic and/or clinical institutions rightly choose titles indicating journal affiliation .Correctly chosen journal titles reflecting a specific subject category, and geographical and societal affiliation are critical for attracting new submissions relevant to the declared scope of interests. Good examples of general journals covering a variety of scientific fields are Iranian Journal of Medical Sciences and Archives of Iranian Medicine, where correctly declared editorial policy and scope oriented toward local issues  allow publication of articles of interest to the local medical community, indexing in global prestigious databases . Publications on diseases rare in this region but common elsewhere  rarely find their home in this journal. In contrast, Rheumatology International publishes articles on a wide range of rare and common rheumatic diseases and therefore attracts authors from all over the world.Journal titles with the term ‘international’ imply much wider geographical representation and scope of interests. For example, Rheumatology , Heart , and Journal of Cardiovascular Medicine .Wide scope of interests is an advantage for a journal pursuing wider visibility. In some cases, the expansion of interests sometimes associated with changing a journal’s title and language can result in internationalization and substantial growth of the journal’s scientific prestige. The relevant examples are high-impact journals such as The Lancet and The New England Journal of Medicine actively publish peer reviewed, well documented, unique, comprehensively discussed, and educational case reports, which, apart from being highly readable, affect marketing of new drugs, enhance pharmacovigilance (detection of adverse drug events) and timely diagnosis of rare disorders  advertisements are disadvantaged in terms of scientific prestige and visibility in most online databases. Citability of a journal and its chances for inclusion in highly selective databases such as MedLine are reduced when editors give preference to the abstracts of meetings. The scientific merit of most biomedical journals diminishes when articles with a low level of evidence  are published in substantial proportions, negatively affecting the journals’ prestige and chances for future citations. The latter is particularly threatening for newly launched and small journals with limited indexing. In contrast, most big journals such as isorders . Interacisorders -19. UnfoIndexing of a scholarly journal in databases, catalogs, and libraries relevant to the subject of the journal is critical for enhancing its quality, attracting audience, and increasing citations. Nowadays, there are many general and specialized indexing services used for ranking journals, individuals, research and academic institutions and even countries. Of these, the most popular and prestigious are indexing services offered by Thomson Scientific (formerly the Institute for Scientific Information). Most scientific journals are either striving to get access to its highly selective Science Citation Index Expanded database or to get the highest possible 2-year Journal Impact Factor (JIF) published by Journal Citation Reports. JIF is viewed as a surrogate measure of journal quality by some experts . HoweverIt seems obvious that editors’ efforts should be directed toward improving publication standards and getting access to many relevant indexing services. Editors of the journals rejected by leading general online databases should put more efforts into attracting better quality publications, approaching alternative indexing services and widening visibility in open access repositories, regional, specialized, and sub-specialized databases.Wider visibility can become a gateway for indexing by prestigious indexing services and libraries. Although there are no specific recommendations, the least editors can do to increase journal visibility and citation chances is to publish comprehensive instructions for authors and to check title pages for inclusion of accurate and informative titles, each author’s affiliation, full address for postal and electronic correspondence, abstracts, keywords, citation options using Uniform Record Locators (URL), and validated references . This inPerhaps the most difficult task is to correctly choose keywords. Reflective words or phrases can be found in the main text of the manuscript. Ideally these should be similar to the indexing terms listed in the relevant vocabulary thesauri such as Medical Subject Headings (MeSH) used by the US National Library of Medicine for indexing articles in PubMed . A numbeReference validation and correct listing is yet another sensitive issue, implicating the correctness of citation tracking and calculation of journal impact factors by Scopus and Web of Science. First of all, it is necessary to choose the format for the references. Both the Harvard and Vancouver systems are widely used, with a preference given to the latter. In the Vancouver system, references are listed in chronological order of their citation in the text and quoted by Arabic numbers . Unless Croatian Medical Journal suggested that timeliness of a small journal publication can be reached by investing more on education of local reviewers, particularly female experts   ,42. As a trials) .To ensure the quality of scholarly publications, editors along with authors, reviewers, and the publisher should pay close attention to every detail, starting from the submission to publishing the final scientific product. Understanding of the role of biomedical journals in disseminating cutting edge information, educating readers, stimulating research activity, and influencing medical practice obliges all those taking part in science editing and publishing to assess available resources and to direct efforts at expanding international outreach and further promoting communication between experts. The process of improving quality of the journal is continuous and equally important for top and low rank, big and small, and general and specialized journals. While well established and widely visible journals are aiming to maintain high editing and publishing standards, new and small journals are struggling to meet basic requirements and to break the vicious cycle of inadequacy associated with poor scientific quality and infrequent submissions in substandard English, lack of international collaboration, inexperienced reviewers, poor representation in relevant libraries and online catalogs, etc . Of courTo overcome poor biomedical science editing, several possible solutions can be suggested. Educating editors and reviewers seems to be the most feasible task which can be fulfilled by professional associations such as WAME, COPE, CSE, EASE, regularly issuing guidelines, publishing teaching materials, organizing online discussions for its members, and arranging scientific and educational meetings worldwide. Regional medical editors associations such as those in the Eastern Mediterranean, Asian Pacific, and some other regions can also play important supportive role. A new approach to improving the quality is emerging in a form of evidence-based biomedical journalism which may distinguish “good” and “bad” journals by employing the established principles of evidence-based medicine .


International Journal of Pediatric Endocrinology (IJPE) was launched to provide the first fully electronic, open access journal for the field in an era of evolution in media and global medical interaction. IJPE was launched with the incredible support of Hindawi Publishing Corporation and has quickly become a leading journal in our field. IJPE has rapidly evolved with the help of our readers and colleagues, to whom we are grateful for choose IJPE as a platform for presenting their work to the world. Since our birthday, we have had nearly 400 submissions and have published 100 reports. IJPE is now the official or affiliated journal of six major pediatric endocrinology societies that encompass more than 80% of the pediatric endocrinologists in the world. Having exceeded our initial goals, it is now time for IJPE to continue its evolution as the premier pediatric endocrine journal by joining forces with the Biomedical Central (BMC) family of journals.Two years ago, the The BMC open access journal group includes more than 100 journals, a number of which are the leading and official journals in their field. BMC journals are highly selective with numerous journals achieving lofty impact factors. BMC features contemporary electronic platforms with electronic links with other related journals, endocrine-related publications, and endocrine society home pages. This electronic system facilitates information sharing for our field at an unmatched level.Excellence, accessibility, expansion, and evolution will be the tenets which will guide IJPE in our new partnership. To achieve excellence, we will continue to be highly selective in the reports we accept. Our goal is the dissemination of novel discoveries, be they in basic science, translational, or clinical investigation. To achieve excellence in publication standards, we will relay on our outstanding Editorial board of leading experts, who will apply high standards in report acceptance.IJPE reports available in full to all with the click of the computer key at no cost. At a time when other pediatric endocrine journals charge nearly a thousand dollars or more for personal subscriptions, IJPE is free and will always remain free for all. Our electronic platform also ensures the near immediate dissemination of IJPE reports accepted for publication, allowing us to avoid lengthy publication delays associated with print in journals.Accessibility will be achieved through a wonderful electronic platform that will make IJPE will continue as we link with other pediatric endocrine societies around the globe. IJPE is currently affiliated with Pediatric Endocrine Society (PES), The Asia Pacific Paediatric Endocrine Society (APPES), Sociedad Chilena de Endocrinology y Diabetes (SOCHED), Indian Society for Pediatric and Adolescent Endocrinology (ISPAE), Korean Society of Pediatric Endocrinology (KSPE), and the Endocrinology Chapter of the Indonesian Pediatric Society. IJPE thus is a platform for the societies to report and disseminate important guideline reports.Expansion of IJPE. As such, I, BMC and our esteemed Editorial Board will continue to strive to make IJPE your journal for your individual studies and ensure that IJPE will be our journal for our field as our journal evolution continues.It is truly our privilege and an honor to publish your work and represent your societies in Scott A. Rivkees, M.D.Professor, Yale UniversityInternational Journal of Pediatric EndocrinologyEditor-in-Chief,


Mangatangi parvum Taylor 2013 and Forsteropsalis pureora Taylor 2013. The holotypes of both species  are from Te Papa Tongarewa, Wellington, New Zealand (MONZ).The International Code of Zoological Nomenclature  requiresForsteropsalis pureroa’ at two places in the original publication. The correct spelling is Forsteropsalis pureora, as used elsewhere and in accordance with the cited type locality of Pureora.The latter species was inadvertently spelt ‘I would like to thank Stephen Thorpe  for bringing these errors to my attention.


To report endothelial corneal graft rejection after administration of topical latanoprost eye drops.Two eyes of two patients with a history of multiple intraocular procedures prior to penetrating keratoplasty developed endothelial graft rejection one month after administration of topical latanoprost. Cystoid macular edema developed simultaneously in one patient.Latanoprost may trigger endothelial graft rejection in susceptible eyes. Latanoprost  has been associated with a number of ocular side effects including increased iris pigmentation, elongation of cilia, hypertrichosis, and skin pigmentation.A 68-year-old woman underwent PKP a few months after complicated cataract surgery in the right eye in 1995. She had a second PKP in the same eye in June 2000. After intraocular pressure (IOP) became uncontrolled, latanoprost was added to her prescription of timolol. Two weeks later, best-corrected visual acuity (BCVA) was 20/400, slit-lamp examination revealed a clear, avascular graft and a quiet eye, IOP was 57 mmHg. A polymethyl methacrylate (PMMA) intraocular lens was observed, centered over an open posterior capsule. Vitreous incarceration in the cataract incision was present superonasally along with extensive iridocorneal adhesions. The optic disc seemed mildly saucerized. Moderate pigmentary changes were evident in the macula. After adding acetazolamide, IOP was reduced to 16 mmHg. Topical dorzolamide was substituted for acetazolamide with maintenance of IOP control. Two weeks later, the patient returned with a decrease in BCVA to counting fingers at 1 m having mistakenly used latanoprost four times daily. Tonometry revealed IOP of 10 mmHg. Sectoral corneal edema, multiple white keratic precipitates, and mild anterior chamber reaction were observed . CystoidA 45-year-old man with a history of bilateral trabeculectomy for primary open-angle glaucoma, underwent repeat trabeculectomy in his right eye with mitomycin C by one of the authors (MAJ). One year later, a third trabeculectomy with adjunctive mitomycin C was performed on the same eye because of uncontrolled IOP. Postoperatively, the cornea decompensated gradually and a PKP was performed. IOP increased gradually after PKP and timolol and dorzolamide were started. At that point, the graft was clear and avascular. Three months after PKP, latanoprost was started because of uncontrolled IOP. One month later, epithelial and endothelial rejection occurred in the same eye. The rejection episode partially responded to topical steroids and cyclosporine. Moderate residual corneal edema and visual acuity of counting fingers prompted a second graft in this eye 11 months after the rejection episode. Five months after the second PKP, the graft remained clear and IOP was under control on timolol and dorzolamide.We observed the occurrence of corneal graft rejection shortly after initiating topical latanoprost in 2 eyes with previous PKP. To our knowledge, this has not been previously reported in the literature.Immunologic graft rejection is particularly common during the first year after PKPSince the early days of development of prostaglandins for treatment of glaucoma, the pro-inflammatory effects of such compounds have been a concern. However, a number of early pilot studiesWe suggest that topical latanoprost may trigger immunologic graft rejection in susceptible eyes. Until further studies are performed, it seems prudent to use topical latanoprost with caution in glaucomatous eyes after PKP, especially in the presence of chronic breakdown of the blood-aqueous barrier and in eyes with other risk factors for graft rejection.


Current Genomics. Their efforts have contributed greatly to the high quality and continuous growth of the journal. Given below is the list of reviewers who reviewed articles for the Journal during 2012: A. CarvalhoAl. GjumrakchB. TaylorC. PagniniE. CornerE. ReszkaJ. ParkJ. BadanoJ. DuranJ. ZhuaJun QinA. ListonM. SzaumkesselM. HaqueM. HarperM. Kauffman.M. XiongP. AdlerP. HerrR. ChahwanR. KohliS. JohnsenU. StelzlBentham Science Publishers would like to thank and appreciate the co-operation from all reviewers for their constructive comments and feedback on the manuscripts submitted to


CCC across all stations was spatially segregated by depth of sampling locations . Accordingly, CCC was correlated with thermal stratification, nitrate and soluble reactive phosphorus . Spatial variability in CCC and temporal trends in taxa abundances were rarely correlative between sampling locations in the same lake indicating significant within lake spatiotemporal heterogeneity. Across all stations, a total of 37 bloom events were observed based on distinct increases in phycocyanin. Out of 97 taxa, a single Microcystis, and two different Aphanizomenon taxa were the dominant cyanobacteria detected during bloom events. The Microcystis and Aphanizomenon taxa rarely bloomed together and were significantly anti-correlated with each other at 9 of 12 stations with Pearson R values of -0.6 to -0.9 (p < 0.001). Of all environmental variables measured, nutrients, especially nitrate were significantly greater during periods of Aphanizomenon dominance while the nitrate+nitrite:SRP ratio was lower. This study shows significant spatial variability in CCC within and between lakes structured by depth of the sampling location. Furthermore, our study reveals specific genotypes involved in bloom formation. More in-depth characterization of these genotypes should lead to a better understanding of factors promoting bloom events in these lakes and more reliable bloom prediction models.Spatial and temporal variability in cyanobacterial community composition (CCC) within and between eutrophic lakes is not well-described using culture independent molecular methods. We analyzed CCC across twelve locations in four eutrophic lakes and within-lake locations in the Yahara Watershed, WI, on a weekly basis, for 5 months. Taxa were discriminated by length of MspI-digested  Microcystis, Anabaena, and Aphanizomenon, while Phormidinium, Planktothrix, Gloeotrichia and others occur sporadically [Cylindrospermopsisraciborskii have been detected recently in northern temperate eutrophic lakes, including this study [In many eutrophic lakes, cyanobacteria are responsible for massive accumulations of biomass, otherwise known as "blooms," whether formed through growth, horizontal and vertical migration, or physical forcings (e.g. wind) ,2. The iadically ,7. In adis study ,8. WhileMicrocystis [The success of freshwater cyanobacteria is attributed to a variety of intersecting circumstances—including warm water temperatures, pH buffering above neutrality, nitrogen fixation, vertical movement via gas vacuoles, carbon/phosphorus/nitrogen storage mechanisms, and colony formation that inhibits predation -13—whichocystis .Variability in cyanobacterial community composition (CCC) has been studied in lakes for decades resulting in a rich understanding of environmental factors involved in promoting their growth (reviewed by ). HoweveIn this study, we investigated variability in CCC on a weekly basis over the course of thirty-seven cyanobacterial bloom events occurring at twelve sampling locations in four eutrophic lakes of the Yahara Watershed, Wisconsin, USA. We used a culture-independent molecular method to characterize CCC and asked whether variability in CCC tracked with physical and chemical lake characteristics both spatially (i.e. within and between lakes) and temporally. In addition, we compared CCC and environmental conditions between bloom events to determine the number and identity of taxa responsible for each bloom event, and the prevailing environmental conditions under which blooms occurred by these cyanobacterial taxa. In the year this study was conducted (2008), Southern Wisconsin experienced the highest precipitation on record over a 24-day period in May-June resulting in record high stream flows (500 years) and significant flooding .No specific permits were required for the described field study, nor were any specific permissions needed to sample the locations. None of the lakes sampled are privately owned, and our sampling did not involve endangered or protected species.The Yahara River connects a chain of four lakes within the Southern portion of the Yahara watershed in South Central Wisconsin, USA . Lake Mewww.gleon.org). The buoy was equipped with a phycocyanin fluorometric sensor , data logger  and an RS-232 modem sending data to a shore base station in near real-time. Additional samples were taken from this location when the phycocyanin fluorescent signal was high (steady increase to >2 volts) suggesting that a bloom event may be underway. Water samples were transported back to the laboratory on ice and filtered through a 47 mm, 0.2 µm pore size, polyethersulfone membrane . Filters were placed into 2 ml cryogenic tubes containing 1 g of autoclaved 2 mm glass beads and stored at -80 °C for DNA extraction. A 50 ml aliquot of sample water was amended with 0.05 ml of concentrated HCl and stored at 4 °C for measurement of total phosphorus (TP) and 50 ml of water was filtered through a 0.7 µm glass fiber filter  and stored at -20 °C for measurement of soluble reactive phosphorus (SRP), nitrate, and nitrite.Integrated samples of the water column receiving photosynthetically active radiation  were taSRP was measured in filtered samples by the ascorbic acid method 4500 PE . TP was cpcB/A genes plus intergenic spacer region were amplified from total community DNA using primers previously published [2, 0.25 mg/ml BSA, 1 unit of GoTaq Polymerase (Promega), and 5 µl of 10X buffer supplied with Taq. The thermocycler protocol was as previously described [2O. A 3 µl aliquot was mixed with 10 µl of formamide and 0.4 µl of a ROX labeled (Carboxy-X-rhodamine) custom size standard (Bioventures) containing DNA fragments ranging from 30-1250 bp. The APISA DNA fragments were sized by capillary electrophoresis using an ABI 3700 sequencer as previously described [CCC was determined based on sizing of MspI-digested PC-IGS gene fragments on an automated sequencer, which we call automated phycocyanin intergenic spacer analysis or APISA. It is a variation on terminal restriction fragment length polymorphism analysis, except that the size of fragments is based on the MspI site as well as length of the intergenic spacer. Sizing on an automated sequencer allows for discriminating fragments that differ by 1-4 bp and an estimate of relative abundance. Briefly, DNA was extracted directly from filters using a xanthogenate-phenol-chloroform protocol previously described . The cpcublished . Each 50escribed . The PCRescribed .Electropherograms were aligned and analyzed using Genemarker® v1.75 as previously described . Peak siin silico using the MspI restriction site. A list of terminal fragment sizes with their corresponding genus classification was then exported from ARB and used as a custom database in the Phylogenetic Assignment Tool (PAT) [An attempt was made to assign OTU’s to genera based on comparison to a library of PC-IGS sequences. We previously provided a sequence alignment and phylogenetic analysis of 271 PC-IGS sequences recovered from the same samples as those analyzed in this study . An addiol (PAT) , which wol (PAT) .For this study we considered a cyanobacterial bloom to be any accumulation of phycocyanin in the photic zone (i.e. the area of the water column sampled), mathematically defined as an increase in phycocyanin 1.5X above a baseline. Each point along the baseline was calculated as a simple moving average (SMA) using all previous observations, except those identified as occurring within a bloom. The SMA is defined as:SN does not include bloom samples. Hence, the first point on the baseline is equal to the first observed phycocyanin concentration and all subsequent points are calculated as the SMA of all previously observed phycocyanin concentrations that were below 1.5X of the baseline. Excluding bloom samples from the SMA calculation prevents stepwise increases in the baseline after each bloom event, which otherwise would underestimate the number of bloom events occurring later in the year.Where ΔT). For the CA and CCA’s, a response model was chosen using indirect or direct gradient analyses, respectively. Biplot scaling was selected with focusing on inter-sample distances. The OTU data was not further transformed and only one outlier was removed. An Analysis of Similarity (ANOSIM) was conducted in Primer v5.0 using a Bray-Curtis dissimilarity matrix. All descriptive statistics, Pearson R correlations, and Mann-Whitney tests were calculated in the R statistical package.All chemical and physical data were log transformed prior to all analyses. Correspondence (CA) and canonical correspondence analyses (CCA) were conducted in CANOCO v5.4 . A matriTrends in water temperature were similar across all stations and ranged from 11.5-30 °C over the sampling period. PZD became shallow at all stations early in June and remained shallow averaging 2.7 +/- 2.0 m for the rest of the sampling period . We defiMyriophyllumspicatum).At all locations, dissolved nutrients were highest in June, well after spring mixing, possibly due to heavy rain events, and again in October due to lake mixing in autumn . Nutrienin silico. There were 94 total OTUs detected, and nine of these could be matched to the PC-IGS sequences digested in silico with MspI . Therefore, the identity of this OTU is ambiguous among these three genera and was not included when summing relative abundances of genera.To identify cyanobacteria, the APISA OTUs were matched to phylogenetically characterized PC-IGS sequences digested with MspI ith MspI . The ninibraries . One APIMicrocystis (Mcy) OTU designated Mcy215 was on average the most abundant in the entire dataset followed by unidentified taxa> AnaAphChr690> Aphanizomenon (Aph) 680> Mcy661> Mcy506> Aph700> Chroococcus (Chr) 352> Chr132, and Cylindrospermopsis (Cyl) 605. Collectively, the Microcystis taxa made up, on average, about half of the relative abundance at each sampling location (51 +/- 9%).The nine OTUs that could be identified accounted for on average 87 ± 14% of the total peak heights detected in any given sample. None of the unidentified OTUs were significantly abundant in any one sample and were rarely detected in more than three samples. However, the sum of relative abundances of all unidentified OTUs was on average the second highest at each sampling station. This suggests that a diverse community of less abundant cyanobacterial taxa exists in these lakes that are not represented by known PC-IGS sequences. The A total of 228 samples were collected across the four lakes and twelve stations (17-26 samples per station). Of these, 197 were analyzed by APISA allowing for an analysis of both temporal and spatial variability in CCC. Less samples were analyzed in Lake Wingra due to lack of PCR amplification of the PC-IGS, which is consistent with lower levels of phycocyanin in this lake . CorrespMicrocystis OTU designated Mcy215 was significantly higher at shallow water stations and was twice as high in the shallowest lake, Lake Wingra than in all other lakes . Variability in CCC along this axis correlated best with nitrate, SRP, and nitrite (p < 0.05) in CCC between several locations in the same lake indicating within lake heterogeneity. Many of these significant differences were between deep and shallow locations . In other words, the same OTU followed the same trend at all three stations. In contrast, with just a few exceptions, individual cyanobacterial taxa in the other three lakes  did not follow the same trend between locations in the same lake at a significance cutoff of p < 0.05. For example, in Lake Kegonsa on Sept. 5th, Aph680 was responsible for a bloom at the KEDH location, but was not detected on the same date, 1.9 km away in the same lake at the KEBE location. Only a few taxa followed similar trends in these three lakes. For example, Cylindrospermopsis in Lake Monona , Aph700 in Lake Kegonsa , and two Aphanizomenon taxa and Chr352 in Lake Wingra. Overall, these data indicate that with the exception of Lake Mendota, most cyanobacterial taxa follow contrasting trends in relative abundance between locations in the same lake.We asked whether relative abundance of individual taxa followed the same trend at different sampling locations in the same lake. The unidentified taxa were not included in this analysis since individual unidentified taxa were only detected on a few sampling days at each location. There was a striking difference between Lake Mendota and all other lakes. In Lake Mendota, the trends in relative abundance for any given cyanobacterium, except for one (i.e. Chr132), were similar at all three stations with Pearson R values of 0.6 or greater  or SRP (R = 0.60-0.85) along the first axis accounting for 21.2-34.9% of the variability . The secSignificant increases in phycocyanin were observed in all lakes during the sampling period resulting in blue-green colored scums on the water surface , primariA bloom event was defined as sustained levels of phycocyanin 1.5X above the simple running average of phycocyanin concentrations not including bloom samples. This definition generally agreed with qualitative observations of water quality during sampling. However, there were several events where this definition grouped multiple, often, lesser phycocyanin increases into one bloom event. These occurred in Lakes Kegonsa and Wingra . Therefop < 0.05 indicating significant within lake bloom heterogeneity. However, the start of the cyanobacterial bloom season at all stations occurred simultaneously, within one to two weeks of each other in mid-June to early-July. This was coincident with increasing water temperature, declining dissolved nutrient concentrations, and an increase in ΔT (The average bloom duration was 29 +/- 25 days. Some blooms lasted for as little as 4 days while others slowly accumulated and then declined over the entire sampling period resulting in a single event lasting > 3 months . Since sse in ΔT .Microcystis and Aphanizomenon dominated (i.e. ≥ 20% relative abundance) most bloom events (Microcystis taxa grew significantly on only a few days in primarily the deepest locations (e.g. MEDH and MODH), but their peak relative abundances did not coincide with most bloom events  and five together and/or with other taxa. Nearly all Aphanizomenon-dominated bloom events (5 out of 7) occurred early in the sampling period (i.e. June and July) and/or occurred prior to the first Microcystis bloom (st or 2nd week of June). Of all stations, only two had a Microcystis dominated bloom early in summer, but these occurred at the end of June and both stations were in Wingra where Aphanizomenon was generally absent. Seven stations did not have an Aphnizomenon- dominated bloom early in summer. In a few blooms, no dominant taxa were present at the peak of the bloom (i.e. none with > 20% relative abundance) indicating multiple taxa contributed to the bloom or the dominant organism could not be detected by our methods.The s bloom . These fMicrocystis and Aphanizomenon were the dominant taxa during most bloom events, they rarely bloomed together and only co-dominated the same bloom event on one occasion (Aphanizomenon and Microcystis taxa were significantly (p < 0.001) anti-correlated with each other at nine of twelve stations with Pearson R values of -0.7--0.9  or taxa (e.g. AnaAphChr690) were significantly anti-correlated with either Aphanizomenon or Microcystis.While 0.7--0.9 . The com October . No otheAphanizomenon taxa, Mcy215 and the sum of Microcystis or Aphanizomenon taxa were significantly correlated with nutrients and/or physical variables at 9 of 12 stations  between periods of Microcystis and Aphanizomenon dominance (p > 0.01). The nitrate plus nitrite (N+N) to SRP ratio (N+N:SRP) also differed between Microcystis and Aphanizomenon abundance (i.e. lower during Aphanizomenon abundance), but was not significant at all stations. Together, these data suggest that Aphanizomenon was most often dominant during periods when nutrient concentrations were relatively high compared to periods of Microcystis dominance, but the ratio of available inorganic N relative to P was low, possibly favoring this nitrogen fixing cyanobacterium. At two of the three stations where Microcystis and Aphanizomenon were not anti-correlated , Aphanizomenon relative abundance was negligible while in the third station (i.e. MOMB), Aphanizomenon and Microcystis were significantly anti-correlated with the exception of June samples.Average dissolved nutrient concentrations, including nitrate, nitrite, and SRP were significantly different  was responsible for most cyanobacterial bloom events across all stations.In this study, we attempted to capture both spatial and temporal variability of CCC in multiple eutrophic lakes and stations using a culture-independent molecular method. We discovered that most bloom events across all lakes and stations were dominated by just three of the more than 90 taxa or genotypes identified . Although other taxa were involved in some bloom events, at least one of these three taxa were involved in all of them. Furthermore, we found that not all Aphanizomenon taxa and occurred within 1-2 weeks of one another at all stations, while most of the subsequent blooms were dominated specifically by Microcystis, Mcy215. Additionally, the Microcystis blooms were not concurrent across stations. This suggests that Aphanizomenon responds to the change in season while Microcystis benefits from a suite of intersecting station- specific conditions. We found that seasonal trends in water column stratification predict Microcystis abundance well in two similar deep water stations in Lake Mendota, but not in any of the other lakes or stations sampled. In neighboring Lake Monona Microcystis was correlated with SRP, but not stratification. However, this was likely due to the fact that 2 of 3 Lake Monona stations were shallow. In other studies, temporal variability in Microcystis has been correlated with both stratification and SRP, but usually only in a single lake or multiple lakes with poor temporal resolution. Hence, heterogeneity in cyanobacterial ecology, genetics, and physiology within and between lakes is likely even greater than currently recognized. We should note that only a subset of all possible environmental variables were measured in this study.With respect to accumulations in cyanobacterial biomass, our observations were consistent with previous work . Blooms We showed that there is significant within lake spatial heterogeneity, particularly with respect to cyanobacterial genetic structure and overall abundance. For example, trends in phycocyanin concentration were not correlative between any two locations and except for Lake Mendota, the relative abundance of individual taxa at locations within the same lake followed contrasting trajectories through time . These dOscillatoriales are often observed to dominate shallow systems [Chroococcales such as Microcystis have been observed to dominate many shallow lakes including Lake Taihu, a well-studied shallow eutrophic lake in Eastern China [Microcystis genera were more abundant in shallow locations, especially Lake Wingra, but also emerged later in the Lake Mendota deep locations when stratification was strong. In a study by Brock et al. (1985) in Lake Mendota, Microcystis were more often observed in deep sediment traps than Aphanizomenon. Thus, strong vertical stability may be important in order for Microcystis maintain significant biomass in the photic zone of deep locations, whereas in shallow locations, the water column in thoroughly mixed with light penetrating throughout. This may be a result of poorer buoyancy control compared to Aphanizomenon, or perhaps Microcystis are better adapted to high light conditions in these lakes.We observed that CCC was significantly segregated between stations according to depth of the water column. Accordingly, of all environmental variables measured, ∆T was most strongly correlated with spatial variability in CCC , Table 2 systems ,44. Howern China . In thisΔT, dissolved inorganic nutrients were also significantly correlated with spatial variability in overall CCC. All shallow stations had slightly lower mean concentrations of standing stock SRP, which may have been due to co-occurrence of macrophytes in these areas. Thus, it appears that nutrient availability and eukaryotic competition may play a larger role in structuring CCC between shallow and deep locations within these lakes than does PZD. This agrees with the average higher coefficient of variation in nutrient levels (0.9-1.6) compared to the PZD (0.4-0.6) at all locations.The affect of depth of the water column on cyanobacterial ecology is well studied and may be explained by light and nutrient availability regulated by water column stratification ,47. In tAphanizomenon and, to a lesser extent, Microcystis quickly increased after the June rain events as nutrients and PZD declined while water temperature increased . The strong pulse of nutrients delivered during these rain events could have disrupted any seasonal trend in CCC, which was not observed in our dataset. Rather the influx of inorganic nutrients, particularly SRP, may have structured CCC during this year. Cyanobacterial blooms of ncreased . Thus, iAphanizomenon and Microcystis. This anti-correlation is primarily due to the occurrence of Aphanizomenon blooms early in summer while Microcystis had peak abundances later in summer into early autumn at most locations  are responsible for producing the bulk of biomass in lakes. In fact, only one of three Microcystis OTUs was responsible for most bloom events indicating that these “species” differ greatly in their ability to dominate the water column. Therefore, the identification of taxa that specifically contribute to blooms at a genetic level is likely to provide a better understanding of CCC and overall cyanobacterial bloom ecology.As we look to forecast the effects of management decisions, climate and land use change on the occurrence and frequency of algal bloom events, it is necessary to characterize taxa responsible for producing this biomass. We can draw some very salient parallels to the infectious disease literature, which is right now focused on the necessity of differentiating bacterial pathogens based on genetic markers rather than phenotypic morphological markers . Should Microcystis, and two different Aphanizomenon taxa were the dominant cyanobacteria detected during all bloom events at all stations including multiple stations in the same lake. The Microcystis and Aphanizomenon taxa were significantly anti-correlated with each other at most stations and Aphanizomenon was more abundant when nutrients were higher suggesting interesting interactions between these genera potentially driven by N2-fixation or other phenotypes . Overall, this study shows that temporal trends in biomass and individual taxa are heterogeneous between lakes and locations in the same lake. Furthermore, the molecular approach shows that just a few individual genotypes were responsible for most bloom events.This study provided the most comprehensive analysis to date of spatial and temporal variability in CCC across multiple lakes and within-lake stations using a culture- independent molecular approach. The CCC across all stations was most strongly segregated by depth of the sampling location and was correlated most strongly with thermal stratification and nutrients. Spatial variability in CCC and temporal trends in taxa abundance were rarely correlative between sampling stations in the same lake indicating significant heterogeneity in the x-y dimensions. More than 90 taxa were identified, yet a single Table S1Results of pair-wise comparisons of cyanobacterial community composition between locations in the same lake using ANOSIM.(DOCX)Click here for additional data file.Table S2Aphanizomenon, or Microcystis taxa and environmental variables.Significant (P<0.05) correlations (Pearson R) between the major bloom forming (DOCX)Click here for additional data file.Figure S1Trends in biological, physical, and chemical variables across all lakes and locations.For each location the top graph represents the sum of the relative abundance of all Microcystis taxa compared to that of Aphanizomenon taxa. Arrows indicate peak bloom dates based on phycocyanin. The second graph shows changes in phycocyanin and water temperature in the photic zone. The photic zone depth (PZD) was estimated from secchi disk depth, which is shown in the third graph along with the difference in water temperature from surface to lake bottom as a measure of water column stratification (ΔT). The fourth graph shows trends in nutrients . and the nitrate+nitrite to SRP ratio (N+N:SRP). Nitrate and nitrite were below detection limits in Lake Wingra.(TIF)Click here for additional data file.Figure S2Cyanobacterial surface scums on Lake Kegonsa, WI, August 2008.(TIF)Click here for additional data file.Figure S3Differences in mean relative abundance of identified taxa between deep and shallow locations.Chr352, Mcy215, and Unmatched taxa are significant differences.(TIF)Click here for additional data file.


Against the backdrop of demographic change and economic reconfiguration, recruiting international students, especially those at tertiary level, has drawn growing attention from advanced economies as part of a broad strategy to manage highly skilled migration. This comparative study focuses on three English speaking countries receiving international students: Canada, the United States, and the United Kingdom. International student policies, in particular entry and immigration regulations, and the trends in student mobility since the late 1990s are examined drawing on secondary data. By exploring the issue from the political economy perspectives, this study identifies distinct national strategies for managing student mobility, determines key factors shaping the environment of student migration in each nation, and addresses the deficiency of human capital theory in the analysis of global competition for high skills.The online version of this article (doi:10.1186/2193-1801-2-132) contains supplementary material, which is available to authorized users. Today’s global economy is characterized as a post-industrial knowledge economy, where a nation’s “knowledge advantage” in cultivating a well-educated, highly skilled, and flexible workforce has been recognized as the most critical asset for economic prosperity  have become a key indicator of innovation  and the European Economic Area (EEA), the UK has traditionally been involved in Europe-wide labour mobility and skill development programs (such as the ERASMUS programme). Besides the commitment to the European higher education market, the UK announced its strategic plans for participating as an ambitious competitor in the global higher education arena though the two Prime Minister’s Initiatives (PMI) launched in 1999 and 2006 respectively. The PMIs set specific goals of recruiting international students through marketing UK education, reducing the dependence on a small number of source countries, and ensuring the quality of student experience from application and visa process to the end of the studies , in which immigration is a fundamental part of the founding myth, historical consciousness and national identity  areas and advanced research programs  of whom 2.7 million (79.1%) studied in OECD nations  Table Table However, the extent to which host countries rely on their leading source countries varies. For instance, the proportion of international students from the top five source countries increased in Canada (from 46.2% to 54.3%) and the US (from 41.6% to 50.0%), but decreased in the UK (from 39.4% to 36.6%) during the past decade Table , which cInternational evidence of student retention can largely be drawn from two sets of data: the first one is retention rate, which is roughly the proportion of international students who gain residence in the country, ideally by cohort; the second is the proportion of residence approvals who are former students in the host country . Very fed Preliminary data show that, in 2009, 74% of all admissions through the CEC were former students  is an important pool of approved status change to either other non-immigrant categories or permanent immigrants. Up to 90% of foreigners receiving immigrant visas for employment are already in the US, especially via the pathway from students in higher education (OPT program), through H-1B visa holders, to permanent residents Dunnett . This pag Therefore, the US did not confront the urgency of reforming its student retention policy; the recent policy provisions associated with post-study work and status change, such as the H-1B advanced degree exemption and the extension of the period of the OPT program, were not initiated as proactive measures to attract international students, but rather additional offers besides the relaxed visa policy in order to re-establish the US popularity and its welcoming image to international students.The US reactive approach to international student migration has also been demonstrated through the absence of proactive measures to adjust its retention policies as a way to attract foreign talent, which is also closely related to the employment-based immigration selection. Though the difficulties associated with the issue of H-1B visas and settlement in the US have been widely criticized, the tight control on residence approvals is not a major obstacle for the country to maintain its attractiveness to international students. For those highly qualified graduates who decidedly want to stay in the country, the status change may not be the most critical concern as the pathway to settlement is embodied in the US employment-based immigrant selection in spite of the long probationary time being non-immigrant residents. The nation has faced little trouble in achieving its immigration goals while avoiding hostile public opinion towards status change of international students, as a significant portion of this temporary category go through an employment-based selection. This research suggests that rather than strictly following a single logic of global human capital, nation states address and cope with the skill challenges in a strategic and political way. The management of international student mobility, among other national strategies aiming at the high skill economy, never exists simply as an economic issue of productivity, but embraces a collective goal of national interests. Host countries’ governments in fact seek to balance the concerns of different stakeholders in order to sustain and strengthen the government’s authority and legitimacy. Therefore, it is not so much whether one immigration system is more effective than another in bringing more skilled workers, but how a country can ensure that its selection criteria are consistent with its specific objectives .fThe consequent soaring inflows of international students to Canada after the terrorist attacks drew attention to a broad range of potential benefits from educating foreigners, especially the strategic role international students play as a pool of skilled workers.gThough there are indeed negative evaluations of foreign student programs in the US (see Borjas


Chiropractic & Osteopathy changes its title to Chiropractic & Manual Therapies in January 2011. This change reflects the expanding base of submissions from clinical scientists interested in the discipline of manual therapy. It is also in accord with the findings of a review of the journal content and a joint venture between the original parent organisation the Chiropractic and Osteopathic College of Australasia and a new partner the European Academy of Chiropractic, which is a subsidiary body of the European Chiropractors' Union. The title change should encourage submissions from all professionals interested in manual therapy including chiropractors, osteopaths, physiotherapists, medical doctors and scientists interested in this field. Chiropractic & Osteopathy (C&O) to Chiropractic & Manual Therapies (CMT). This change reflects the expanding base of submissions from clinical scientists interested in the discipline of manual therapy. It is also in accord with the findings and changes suggested by Coulter and Khorsan in their invited review of our journal. They noted that the articles in C&O are overwhelmingly from chiropractors and proposed several recommendations including a change in the journal title [This first paper in 2011 marks some significant changes for the journal. The first and most noticeable change is the title from Chiropractic & Osteopathy (C&O) the official journal of the Chiropractic and Osteopathic College of Australasia (COCA) and the EAC.The decision to change the title was also influenced by successful negotiations with the European Academy of Chiropractic (EAC) to enter into a joint venture agreement on the journal. The EAC also encouraged a name change. This agreement with the EAC and its parent body the European Chiropractors' Union (ECU) was signed in June 2010 making the journal COCA is a non-profit, member-based organisation that provides continuing education to its members predominantly in Australia (COCA website ). COCA aThe ECU is a Union of nineteen European chiropractic associations from Belgium, Cyprus, Finland, France, Germany, Great Britain, Greece, Iceland, Ireland, Italy, Liechtenstein, Luxembourg, The Netherlands, Norway, Poland, Portugal, Spain, Sweden, and Switzerland (ECU website ). The ECThe EAC's purpose is to act as the academic arm of its parent organisation the ECU. It is responsible for the academic promotion of the chiropractic profession in Europe and liaises with other academic institutions (EAC website ).Chiropractic & Manual Therapies to remain an international open access journal without charge to authors during this time. Further extension of this charging policy will be discussed in early 2011. This is unusual as the vast majority of online journals charge authors to publish. The second reason to pursue a joint venture was that it provides a broader international supporter base for the journal, providing wider readership and an anticipated increase in the number of high quality manuscripts submitted. Since 2005 the journal has received over 320 submissions and accepted 130 of these for publication, rejecting or suggesting withdrawal of approximately 60% mainly due to poor methodological and scientific quality found at peer review.There were several reasons to pursue a joint venture; first were economies of scale regarding funding for the journal with EAC now contributing half the expenses incurred. This has allowed COCA and EAC to cover the cost of article-processing charges for all manuscripts submitted before April 2011. This will enable The joint venture and re-naming of the journal enhances it as a major international publication by means of greater global acceptance and marks the start of the next phase of growth of the journal including application for an impact factor and MEDLINE listing.There have also been key changes to the journal's editorial team with two new Associate Editors from Europe joining the team. Professor Charlotte Leboeuf-Yde (Denmark) and Dr Sidney Rubinstein (The Netherlands) add to the depth and breadth of the existing Associate Editorial team which includes Dr Simon French and Associate Professor Melainie Cameron , and Professor Stephen Perle (USA). The position of Editor-in-Chief remains unchanged with Dr Bruce Walker in Australia. The Editorial Board has 42 members and is extensive in its skills, experience and diversity .Chiropractic & Manual Therapies". We look forward to your comments as readers and your submissions as authors.Given these historic changes, we predict an increase of high quality submissions over the coming years with continued growth and international positioning of our newly named journal "


The series of the biennial European congresses on Telepathology reached with this Venice edition its 11th appointment: more than 20 years of research in a continuously growing field. It is also the fifth time the congress brings the additional name of International Congress of Virtual Microscopy: eight years ago the International Academy of Telepathology decided to recognize this way the importance of virtual microscopy, also called Whole Slide Imaging, in the renovation of the telepathology scenario. In the last congress the International Academy of Digital Pathology was also founded, to replace and continue the great work of the International Academy of Telepathology that organized most of this congress series. This step recollects under the single term “digital pathology” all the technologies that are tranforming the traditional, “analog” pathologist in a digital professional that work on digitized slides, with software tools that enable to better exploit his/her knowledge, leaving routine details to the computers and networks. Once slides are digitized, a whole bunch of applications come natural and available: telediagnosis, teleconsultation, e-learning, long term storage, up to image analysis, with the forthcoming field of digital immunohistochemistry. No need to carry out additional operations: slides are ready for further digital treatment, present and future.Digital Pathology is made possible not only thanks to the research grown in the last many years and presented at every Congress of this series. Every year the processors power increases, memory becomes larger and larger, and thus computers become more and more adequate to such large, information-filled objects that are the so-called digital slides.This 2012 Congress hosted more than 80 presentations from 23 countries of the world. It represents the current state of the art in the field of digital pathology: what can be read in the present proceedings will represent the future of Pathology in the short, mid and even long term, thus providing insights on a new world which the traditional and crucial work of the pathologist should remain under his/her own control, made easier and more productive through digital tools.


In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV) is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes . The CD4+ T-cell epitopes that are commonly conserved (∼556) were further screened against the Immune Epitope Database (IEDB) to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556) epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62%) when compared with other ethnicities (57.77% to 94.84%). In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs. On March 31, 2013, the China Center for Disease Control and Prevention identified a human infection by a novel avian influenza A virus (H7N9), one with multiple avian genetic reassortments In vitro studies demonstrated the protective role of CD4+ T-cell reactivity against previously the unencountered avian influenza (H5N1) strain; this protection was shown to be due to the presence of commonly conserved and shared epitopes with seasonal influenza strains, H1N1 and H3N2 The avian specific genome and the antigenically distinct nature of H7N9 surface glycoproteins, led to the absence of protective neutralizing antibodies for H7N9 in the human population Hence, preexisting CD4+ T-cell immunity can potentially limit the disease severity of H7N9 infection in antibody naïve population. Our study examines the likely presence of preexisting CD4+ T-cell immunity towards H7N9 in the human population, derived from previous exposures with human IAV subtypes . We conducted comparative whole proteome analyses and a large-scale immunoinformatics analyses to predict and identify the commonly conserved and shared CD4+ T-cell epitopes of H7N9 with human IAV subtype strains. Further, all the commonly conserved predicted epitopes among avian and human IAVs (henceforth referred as “commonly conserved”) were screened against the IEDB  to validate their immunogenic potential. Next, we conducted population coverage analysis with the commonly conserved CD4+ T-cell epitopes in the context of Human leukocyte antigen (HLA) DRB1 alleles to understand the likely distribution of preexisting CD4+ T-cell immunity in different ethnic groups, and further discussed with previously reported influenza mortality/morbidity rates.All eleven protein segments, namely polymerase B2 (PB2), polymerase B1 (PB1), PB1-F2, polymerase (PA), HA, nucleocapsid protein (NP), NA, matrix proteins 1 & 2 (M1 & M2), and nonstructural proteins 1 & 2 (NS1 & NS2) of H7N9 isolated from humans in China during 2013 were obtained from the Global Initiative on Sharing All Influenza Data (GISAID) Epiflu database (Table S1 in ROC>0.9) A comprehensive evaluation of the Major Histocompatibility Complex (MHC) class II or HLA class II peptide binding prediction servers reported NETMHCIIPAN (epitope binding prediction tool); they based their evaluation in terms of the area under the receiver operating characteristic curve  Predicted CD4+ T-cell epitopes of H7N9 are matched with the sequence database of each subtype of IAVs i.e. H1N1 1918–76, seasonal H1N1 1977–2009, pandemic H1N1 2009–2013, H2N2 1957–1968, and H3N2 1968–2013. Epitopes that have ≥90% conservancy are categorized into conserved epitopes of H7N9 with each of the subtype. Epitopes that have <90% conservancy are regarded as epitopes unique to H7N9. Data thus generated is used to calculate whether conserved/unique epitopes in H7N9 are more/less than expected in H7N9 than other strains; 2) Each subtype specific predicted CD4+ T-cell epitopes are matched with the database of H7N9 sequence database. Epitopes that have ≥90% conservancy are categorized into conserved epitopes of specific subtype compared to H7N9. Epitopes that have <90% conservancy are regarded as epitopes unique to specific subtype compared to H7N9. We used two-tailed Chi-square test to compare the observed and expected conserved and unique epitopes.in-vitro ) and in-vivo  assays. So, comparing conserved predicted CD4+ T-cell epitopes with the experimentally defined CD4+ T-cell epitope datasets (IEDB) would help in assessing for possible preexisting immunity The predicted CD4+ T-cell epitopes of H7N9 were screened against the IEDB repository, which contains the experimentally defined epitope information on the B-cell, and T-cell of various pathogens present in the published literature Commonly conserved CD4+ T-cell epitopes among avian and human IAVs were screened through a population coverage analysis tool Amino acid (AA) sequences of H7N9 HA and NA shared 39.2% to 47.2% and 41.6% to 45.4% sequence homology, respectively with HA and NA proteins of IAVs . When coOverall, conserved epitopes of internal proteins were less than expected, and unique epitopes of internal proteins were more than expected between H7N9 vs. each of other IAVs. This could be due to the distinct genetic nature of H7N9 when compared to other IAV subtypes. This reasoning is exemplified when H7N9 was compared to the oldest strain i.e. H1N1 1918 (p = 0.0001). For H2N2 and pandemic 2009 H1N1, the results were not significant (p = 0.7242)  experimentally defined CD4+ T-cell epitopes contain CD8+ T-cell epitopes as presented in column 4 (D) of HLA alleles likely bind to highly conserved regions of viral proteins H7N9 remains a global public health concern because of its pandemic potential: its persistent evolution Based on our population coverage analyses, it can be said that preexisting CD4+ T-cell immunity to H7N9 virus varies across different ethnicities especially with lower coverage observed in indigenous population . This coPrevious studies have reported, epitopes that can generate both CD4+ and CD8+ T-cell responses due to their sharing of epitope regions are particularly suitable as vaccine antigens and generate robust immune responses Our study has several limitations that should be considered when interpreting findings of our study. Most notably, the binding affinity between epitope-HLA predicts the potential epitope, which is not necessarily reflective of T-cell response. Therefore, T-cell proliferations assays are needed to evaluate the predicted epitopes. Nevertheless, our study provides compelling experimental evidence from published reports and epitope data repository (IEDB). Next, our epitope prediction analysis was restricted to only fourteen HLA-DRB1 alleles - albeit highly prevalent ones - and could be extended to other HLA class II genes: HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DP and HLA-DQ. The updated NETMHCIIPAN 3.0 predictor To conclude, this study demonstrates the likely evidence for preexisting cross-reactive CD4+ T-cell immunity directed towards commonly conserved epitopes within internal proteins of H7N9 in different ethnicities due to previous exposures to different IAVs either through natural infections or through the seasonal influenza immunizations. The study also provides insights into vulnerability of indigenous population to H7N9 virus in case of H7N9 pandemic. This information is crucial for public health policy people in targeting priority groups for immunization programs. Information on overlapping immunogenic CD4+ and CD8+ T-cell epitopes that are commonly conserved within internal proteins is also useful towards the design of universal vaccines against emerging influenza viruses.File S1Supporting Tables. Table S1. Avian influenza A(H7N9) virus gene segments sequences isolated (from human) in 2013 from China used in the study (collected from GISAID Epiflu Database). Table S2. Protein sequences of human IAV subtypes used in the analysis. Table S3. Conserved and unique predicted CD4+ T-cell epitopes of H7N9 in comparison with human IAVs. Table S4. CD4+ T-cell epitopes that are commonly conserved between avian H7N9 and human IAV subtypes and their experimental verification using IEDB. Table S5. Experimentally defined CD8+ T-cell epitopes nested within commonly conserved CD4+ T-cell epitopes.(DOC)Click here for additional data file.


The left internal mammary artery (LIMA) is the choice for grafting of the left anterior descending coronary artery (LAD). One possible mechanism of the rare graft failure involve the presence of competitive flow.105 patients who had undergone coronary bypass grafting between 1998 and 2000 were included in this observational study. The recatheterizations were performed 28 months after the operations. The rate of patency the LIMA grafts was determined, and the cases with graft failure were analyzed.The LIMA graft was patent in 99 patients (94%). Six patients (6%) exhibited diffuse involution of the graft (string sign). The string sign was always associated with competitive flow as the basis of the LIMA graft involution. In one case quantitative re-evaluation of the preoperative coronary angiography revealed merely less than 50% diameter stenosis on the LAD with a nonligated side-branch of the LIMA. At recatheterization in two patients the pressure wire measurements demonstrated only a non-significant decrease of the fractional flow reserve (0.83 and 0.89), despite the 53% and 57% diameter stenosis in the angiogram. Another patient displayeda significant regression of the LAD lesion between the pre- and postoperative coronary angiography (from 76% to 44%) as the cause of the development of the competitive flow. In one instance, a radial artery graft on the LAD during a redo bypass operation resulted in competitive flow in the radial graft due to the greater diameter than that of the LIMA. In a further patient, competitive flow developed from a short sequential part of the LIMA graft between the nonsignificantly stenosed diagonal branch and the LAD, with involution of the main part of the graft to the diagonal branch.The most common cause of the development of the string sign of a LIMA graft due to competitive flow is overassessment of the lesion of the LAD. Regression of a previous lesion or some other neighboring graft can also cause the phenomenon. Prospective angiography in the Bypass Angioplasty Revascularization Investigation trial indicated a 91.6% 1-year patency (< 50% stenosis) for left internal mammary artery (LIMA) grafts. The atherosclerosis of LIMA grafts is rare, and the long-term patency rate of left LIMA-to-left anterior descending (LAD) coronary artery grafts is approximately 90% .The high patency of the LIMA-to-LAD graft also leads to an improved clinical outcome. Extensive observational studies showed that patients who received a LIMA-to-LAD graft had a better survival, and experienced fewer adverse cardiac events as compared to patients who received only saphenous venous grafts (SVGs) ,4.However, there are increasing reports of LIMA graft failure due to diffuse narrowing.Barner described the longitudinal thinning of IMA grafts in 1974, referring to it as "disuse atrophy", because the native coronary arteries to which the IMAs were anastomosed appeared to be patent and to have good flow . SeveralThe most common cause of the distal narrowing phenomenon appears to be grafting of the LIMA to a coronary artery with noncritical stenosis (< 50%), but several other causes for this phenomenon have been emerged, including damage during harvesting and mobilization of the LIMA, spasm, inflammation as part of a post-pericardiotomy syndrome or a steal phenomenon arising from a large undivided proximal branch of the LIMA ,8.CABG to moderately stenotic target vessels may lead to competitive flow between the native vessel and the graft. Because of individual variations in the effects of stenotic lesions on the coronary flow during resting and exercise conditions and variations in the ability of the LIMA graft to adapt to the flow requirements, there is some controversy as regards the implication of competitive flow on the patency of LIMA bypass grafts -11.Our present aim was to investigate the frequency of string sign of LIMA grafts in a series of patients 2-4 years after bypass surgery and to analyze the cases with regard to the role of competitive flow.105 patients  operated on between 1998 and 2000 were enrolled in this observational study. All of them had received a LIMA graft to the LAD, individually or sequentially with the diagonal branch; 1-3 further distal SVG anastomoses or radial grafts were applied, with an average of 3.1 ± 1 distal anastomoses. The recatheterizations, performed 28 ± 11 months after the operations, were indicated by the clinical symptoms.The rate of patency of the LIMA grafts was determined, and the cases with LIMA graft failure were analyzed.The native coronary artery stenosis and graft patency were evaluated independently by expert readers according to the American Heart Association guidelines. The most severe stenosis in the luminal diameter of the coronary artery proximal to the anastomotic site was regarded as stenosis of the target coronary branch.QCA was performed with Philips Integris software from multiple projections in all patients. Reference diameter, minimal luminal diameter, and stenotic diameter were calculated, using the guiding catheter as a scaling device. The most extreme values were chosen for the study. The measurements were carried out both retrospectively on the preoperative coronary angiography and on the index angiography obtained during the recatheterization.Competitive flow was analyzed by the method of Nakajima et al.: the target coronary branch and anastomotic site are clearly opacified in the native coronary angiography, but not in the graft angiography. Selective LIMA angiography  was an inclusion criterion of the study ,13.Pd/Pa at maximal hyperemia, where Pd is the mean distal pressure in the coronary artery (recorded by the pressure wire) and Pa is the mean aortic pressure (recorded by the guiding catheter).After the administration of 5000 U of heparin, a left coronary guiding catheter was advanced in the left main coronary ostium. 100 μg of nitroglycerine was administered intracoronarily, and a 0.014-inch sensor-tipped pressure guidewire  was advanced to the tip of the guiding catheter. After equal pressures were confirmed at that location, the wire was advanced into a coronary artery. 100 μg of adenosine was administered intracoronarily to induce maximum coronary hyperemia. FFR was calculated by the ratio Six of the 105 patients (6%) exhibited diffuse involution of the graft (string sign). These cases were analyzed individually.A 60-year-old male patient who had participated in CABG 4 years previously  underwent repeated coronary angiography because of chest pain and a positive stress test. The angiography revealed an unligated thick side-branch of the left mammary artery with a high run-off, which probably contributed to the string sign of the main branch of the mammary graft Figure . The posA 62-year-old male, who had undergone bilateral mammary bypass grafting on the LAD and the right coronary artery (RCA) 4 years earlier. Coronary angiography showed an almost occluded LIMA graft (string sign) Figure  with 50-A 61-year-old man after an inferior myocardial infarction underwent surgical revascularization involving a LIMA graft on the LAD and a venous graft on the aberrant left circumflex artery (LCx) from the right Valsalva sinus. One year later, the repeated coronary angiography detected string sign of the LIMA graft Figure . and totst obtuse marginal branch (OM), -RCA), a 65-year-male patient was recatheterized because of the recurrence of angina-like symptoms. The venous grafts were occluded, while the LIMA graft was widely patent, with an intermediate lesion in the run-off under the anastomosis of the LIMA. A total arterial revascularization redo operation was decided on, and radial grafts were applied on the LAD, OM and RCA. After 3 years repeated coronary angiography revealed the string sign of the previously patent LIMA graft because the competitive flow of the new radial graft supplied the LAD more intensively than the previous LIMA graft , a 75-year-old man underwent recatheterization because of angina-like symptoms. Coronary angiography showed the string sign of the LIMA graft, while the venous grafts were patent  excluded s significant flow limitation of the stenoses. Of the 6 cases demonstrating the string sign, 3 (50%) had nonsignificant stenosis according to the FFR or QCA criteria.The FFR  has been shown to be an accurate and lesion-specific index for determining if an intermediate stenosis is functionally significant and responsible for reversible ischemia. A threshold value of 0.75 clearly distinguishes lesions responsible (FFR < 0.75) or not responsible (FFR ≥ 0.75) for reversible ischemia during exercise. On the basis of the published data, our observations are in line with the value of the functional assessment of lesion severity by FFR measurement as a potential guide for a decision concerning grafting of an intermediate lesion .In 3 cases, we identified relatively rare sources of the competitive flow in the background of the string sign: a new radial graft on the LAD, significant regression of the LAD lesion, and a sequential LIMA graft to the diagonal branch without a significant lesion.Our results suggest that the most common cause of the string sign is a functionally nonsignificant lesion on the target vessel, but other scenarios leading to competitive flow must also be considered. Table Even though previous observations did indicate clinical relevance of an occluded bypass graft on a nonsignificant lesion, we consider that careful analysis of the clinical scenarios is mandatory for a correct decision regarding grafting: an operation that is too early may lead to the inappropriate use of grafts without prevention of the consequences of the future progression of the disease.Written informed consent was obtained from patients.The authors declare that they have no competing interests.RK participated in the design and coordination of the study. ZG participated in coordination of the study. TU participated in evaluating the results. GS participated in choosing the cases. IR participated in choosing the cases. TS participated in choosing the cases. IH participated in drawing conclusions. IE participated in coordination of the study. AP participated in choosing the cases. ZK participated in all part of the study. All authors read and approved the final manuscript.


There is currently no functioning national antibiotic policy or a national policy to contain antimicrobial resistance in India.“A Roadmap to Tackle the Challenge of Antimicrobial Resistance –the first ever joint meeting of Medical Societies and other stakeholders in India” was held at Chennai on 24th August 2012. The consensus of this historic event was “The Chennai Declaration” which was published in the Indian Journal of Cancer in December 2012.1. The “Roadmap symposium”, per se received extensive coverage in news papers and magazines like “Nature”.2. Within 2 months of publication of the “Declaration” reputed journal like CID, Lancet ID, JAMA and BMJ published reviews and editorials.3. Reviews by many other international and Indian journals will be published in the coming months.4. Popular newspapers in India wrote about the article (“The Hindu” wrote reviews on the document “thrice”).5. This document is already submitted to the Government and is currently being studied by the highest officials. As a result of the Chennai declaration Ministry of Health (MOH) issued an advertisement regarding antibiotic usage in many Indian news papers. This is only a beginning of a series of changes.6. The document has also caught serious attention of high level political circles.7. The article is already accessed by more than 1400 visitors till date from the parent journal website in which it was published. This is in addition to more than 5000 viewers through the ISCCM news letter and also by more than 10,000 physicians in the country, through Association of physicians of India conference update.1. The article, within 2 and a half month of publication has literally created a stir among the Indian and international scientific media, public media and the authorities.2. The paper has in fact changed the attitude of the Indian government towards resistance issue.3. The declaration has provided an opportunity to the international community to view the problem of antimicrobial resistance in developing countries in a different perspective-A “practical and not a perfect policy” being the ideal approach.The Chennai Declaration is a historic document and will be the driving force behind an antibiotic policy in India and other developing countries.None declared.


Advanced atherosclerosis or thrombosis of iliac vessels can constitute an absolute contraindication for heterotopic kidney transplantation. We report the case of a 42-year-old women with end-stage renal disease due to lupus nephritis and a history of bilateral thrombosis of iliac arteries caused by antiphospholipid antibodies. Occlusion had been treated by the bilateral placement of wall stents which precluded vascular anastomosis. The patient was transplanted with a right kidney procured by laparoscopic nephrectomy from her HLA semi-identical sister. The recipient had left nephrectomy after laparoscopical transperitoneal dissection. The donor kidney was orthotopically transplanted with end-to-end anastomosis of graft vessels to native renal vessels and of the graft and native ureter. Although, the patient received full anticoagulation because of a cardiac valve and antiphospholipid antibodies, she had no postoperative complication in spite of a short period of delayed graft function. Serum creatinine levels three months after transplantation were at 1.0 mg/dl. Our case documents that orthotopical transplantation of laparoscopically procured living donor kidneys at the site of recipient nephrectomy is a feasible procedure in patients with surgical contraindication of standard heterotopic kidney transplantation. We report the case of a 42-year-old woman who underwent orthotopic renal transplantation for the first time, using a kidney from her sister. The patient had developed end-stage renal disease secondary to lupus nephritis. She had a medical history of bilateral thrombosis of both common and external iliac arteries due to lupus anticoagulant and antiphospholipid antibodies that had required bilateral percutaneous angioplasty with wall stenting. The medical workup had documented thrombosis of both iliac veins and of the lower portion of the lower part of the inferior vena cava as well as extensive atherosclerotic lesions of the abdominal aorta. In addition, she had a history of mitral valve replacement with a St. Jude prosthetic valve and received anticoagulation therapy with acenocoumarol. The patient had an HLA semi-identical sister who was willing to donate a kidney. The donor workup had documented a slightly lower tubular mass of the right kidney which was chosen for procurement. The “classic” extraperitoneal pelvic transplantation of a kidney graft was contraindicated because of stented iliac arteries and extended atheromatosis of the aorta . An alteThe graft was procured by laparoscopic right donor transperitoneal nephrectomy with utilization of linear stapler Endo-GIA as previously described . The warThe recipient was placed in a modified lateral decubitus position and The native renal vessels were found to be sufficient and were used for the end-to-end anastomoses with prolene 6/00 for the artery and prolene 5/00 for the vein.The left native ureter was then spatulated and anastomosed in an end-to-end fashion to the transplant ureter with vicryl 3–0, over double J stent. A lombonephropexy of the graft was performed and a silicone Jackson-Pratt drain was inserted. The abdominal wall was closed using running vicryl 2–0 suture for the peritoneum, interrupted vicryl 0 suture for the muscle, and running vicryl 1 for the aponeurosis, and the skin incisions were closed with intradermal suture. The second warm ischemia time was 17 minutes and blood loss in the recipient was 15 mL. 2, respectively.At the moment of transplantation, the patient had maintenance immunosuppression with azathioprine and steroids for her systemic lupus erythematosus. Basiliximab and tacrolimus were added for prevention of acute graft rejection. The patient had delayed graft function up to day 4 but did not require renal replacement therapy because of the residual function of her native kidney. Anticoagulation consisted first of low molecular weight heparine (enoxaparin 20 mg per day) with resumption of acenocoumarol on postoperative day 6. The only medical complication was a urinary infection with Pseudomonas Aeruginosa treated with ciprofloxacine. The patient left the department two weeks after transplantation with a serum creatinine of 1.2 mg/dL. The double-J stent was removed 4 weeks after transplantation. Three months after transplantation a control angio-MRI showed normal a normal kidney and graft vessels . At thisWe present a first case of orthotopic transplantation of a living-donor kidney using laparoscopic techniques for nephrectomy of both the donor and recipient kidneys in young patients with complex vascular disease contraindicating classical heterotopic transplantation. Our case demonstrates that these surgical procedures permit successful renal transplantation in selected candidates that would otherwise be forced undergo life-long renal replacement therapy.We chose laparoscopic donor nephrectomy as these technique better aesthetic outcomes, a shortened hospital stay and overall better quality of life as compared to the open procedure while resulting in equivalent graft outcomes . In addiWe chose a laparoscopic technique for recipient nephrectomy to minimize surgical trauma and the risk of bleeding in this patient treated with chronic anticoagulation because of a metallic prosthetic valve and taking in the consideration that the postoperative complications after classic lumbotomy or mini-incision open donor nephrectomy described in 12% of cases , 8. The In summary our case shows that living donor orthotopic kidney transplantation with laparoscopic donor and recipient nephrectomy is a feasible procedure associated with low morbidity and excellent graft outcome that can allow successful transplantation in patients with surgical contra-indications to classical heterotopic transplantation.