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1.  Something going on in Milan: a review of the 4th International PhD Student Cancer Conference 
ecancermedicalscience  2010;4:198.
The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19–21 May 2010 http://www.semm.it/events_researchPast.php
The Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.
The core participanting institutes included: European School of Molecular Medicine (SEMM)—IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam
‘You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!’ Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that’s how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.
The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19–21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.
The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch with other prestigious research centres and to create connections for future post docs or job experiences. And last but not least, it is a golden chance for penniless PhD students to spend a couple of extra days visiting a foreign country (this motivation will of course never be voiced to supervisors).
The network of participating institutes has a three-nation core, made up of the Netherlands Cancer Institute, the Italian European School of Molecular Medicine (SEMM) and five UK Cancer Research Institutes (The London Research Institute, The Cambridge Research Institute, The Beatson Institute for Cancer Research in Glasgow, The Patterson Institute for Cancer Research in Manchester and the MRC Gray Institute for Radiation Oncology and Biology in Oxford).
The conference is hosted and organised every year by one of the core institutes; the first was in Cambridge in 2007, Amsterdam in 2008 and London in 2009, this year was the turn of Milan.
In addition to the core institutes, PhD students from several other high-profile institutes are invited to attend the conference. This year participants applied from the Spanish National Cancer Centre (CNIO, Madrid), the German Cancer Research Centre (DKFZ, Heidelberg), the European Molecular Biology Labs (EMBL, Heidelberg) and the San Raffaele Institute (HSR, Milan). Moreover four ‘special guests’ from the National Centre for Biological Sciences of Bangalore (India) attended the conference in Milan. This represents a first step in widening the horizons beyond Europe into a global worldwide network of talented PhD students in life sciences.
The conference spread over two and a half days (Wednesday 19th to Friday 21st May) and touched on a broad spectrum of topics: from basic biology to development, from cancer therapies to modelling and top-down new generation global approaches. The final selection of presentations has been a tough task for us organisers (Chiara Segré, Federica Castellucci, Francesca Milanesi, Gianluca Varetti and Gian Maria Sarra Ferraris), due to the high scientific level of the abstracts submitted. In the end, 26 top students were chosen to give a 15-min oral presentation in one of eight sessions: Development & Differentiation, Cell Migration, Immunology & Cancer, Modelling & Large Scale approaches, Genome Instability, Signal Transduction, Cancer Genetics & Drug Resistance, Stem Cells in Biology and Cancer.
The scientific programme was further enriched by two scientific special sessions, held by Professor Pier Paolo di Fiore and Dr Giuseppe Testa, Principal Investigators at the IFOM-IEO-Campus and by a bioethical round table on human embryonic stem cell research moderated by Silvia Camporesi, a senior PhD student in the SEMM PhD Programme ‘Foundation of Life Science and their Bioethical Consequences’.
On top of everything, we had the pleasure of inviting, as keynote speakers, two leading European scientists in the fields of cancer invasion and biology of stem cells, respectively: Dr Peter Friedl from The Nijmegen Centre for Molecular Life (The Netherlands) and Professor Andreas Trumpp from The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (Heidelberg).
All the student talks have distinguished themselves for the impressive quality of the science; an encouraging evidence of the high profile level of research carried out in Europe. It would be beyond the purposes of this report to summarise all 26 talks, which touched many different and specific topics. For further information, the Conference Abstract book with all the scientific content is available on the conference Web site (http://www.semm.it/events_researchPast.php). In what follows, the special sessions and the keynote lectures will be discussed in detail.
doi:10.3332/ecancer.2010.198
PMCID: PMC3234021  PMID: 22276043
2.  The Chilling Effect: How Do Researchers React to Controversy? 
PLoS Medicine  2008;5(11):e222.
Background
Can political controversy have a “chilling effect” on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies.
Methods and Findings
Drawing on interview (n = 30) and survey data (n = 82), this study examines the reactions of scientists whose National Institutes of Health (NIH)-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were “a waste of taxpayer money.” The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely.
Conclusions
These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events.
Drawing on interview and survey data, Joanna Kempner's study finds that political controversies shape what many scientists choose not to study.
Editors' Summary
Background.
Scientific research is an expensive business and, inevitably, the organizations that fund this research—governments, charities, and industry—play an important role in determining the directions that this research takes. Funding bodies can have both positive and negative effects on the acquisition of scientific knowledge. They can pump money into topical areas such as the human genome project. Alternatively, by withholding funding, they can discourage some types of research. So, for example, US federal funds cannot be used to support many aspects of human stem cell research. “Self-censoring” by scientists can also have a negative effect on scientific progress. That is, some scientists may decide to avoid areas of research in which there are many regulatory requirements, political pressure, or in which there is substantial pressure from advocacy groups. A good example of this last type of self-censoring is the withdrawal of many scientists from research that involves certain animal models, like primates, because of animal rights activists.
Why Was This Study Done?
Some people think that political controversy might also encourage scientists to avoid some areas of scientific inquiry, but no studies have formally investigated this possibility. Could political arguments about the value of certain types of research influence the questions that scientists pursue? An argument of this sort occurred in the US in 2003 when Patrick Toomey, who was then a Republican Congressional Representative, argued that National Institutes of Health (NIH) grants supporting research into certain aspects of sexual behavior were “much less worthy of taxpayer funding” than research on “devastating diseases,” and proposed an amendment to the 2004 NIH appropriations bill (which regulates the research funded by NIH). The Amendment was rejected, but more than 200 NIH-funded grants, most of which examined behaviors that affect the spread of HIV/AIDS, were internally reviewed later that year; NIH defended each grant, so none were curtailed. In this study, Joanna Kempner investigates how the scientists whose US federal grants were targeted in this clash between politics and science responded to the political controversy.
What Did the Researchers Do and Find?
Kempner interviewed 30 of the 162 principal investigators (PIs) whose grants were reviewed. She asked them to describe their research, the grants that were reviewed, and their experience with NIH before, during, and after the controversy. She also asked them whether this experience had changed their research practice. She then used the information from these interviews to design a survey that she sent to all the PIs whose grants had been reviewed; 82 responded. About half of the scientists interviewed and/or surveyed reported that they now remove “red flag” words (for example, “AIDS” and “homosexual”) from the titles and abstracts of their grant applications. About one-fourth of the respondents no longer included controversial topics (for example, “abortion” and “emergency contraception”) in their research agendas, and four researchers had made major career changes as a result of the controversy. Finally, about 10% of respondents said that their experience had strengthened their commitment to see their research completed and its results published although even many of these scientists also engaged in some self-censorship.
What Do These Findings Mean?
These findings show that, even though no funding was withdrawn, self-censoring is now common among the scientists whose grants were targeted during this particular political controversy. Because this study included researchers in only one area of health research, its findings may not be generalizable to other areas of research. Furthermore, because only half of the PIs involved in the controversy responded to the survey, these findings may be affected by selection bias. That is, the scientists most anxious about the effects of political controversy on their research funding (and thus more likely to engage in self-censorship) may not have responded. Nevertheless, these findings suggest that the political environment might have a powerful effect on self-censorship by scientists and might dissuade some scientists from embarking on research projects that they would otherwise have pursued. Further research into what Kempner calls the “chilling effect” of political controversy on scientific research is now needed to ensure that a healthy balance can be struck between political involvement in scientific decision making and scientific progress.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050222.
The Consortium of Social Science Associations, an advocacy organization that provides a bridge between the academic research community and Washington policymakers, has more information about the political controversy initiated by Patrick Toomey
Some of Kempner's previous research on self-censorship by scientists is described in a 2005 National Geographic news article
doi:10.1371/journal.pmed.0050222
PMCID: PMC2586361  PMID: 19018657
3.  2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research 
BMC Genomics  2010;11(Suppl 3):I1.
Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT Austin), Dr. Aidong Zhang (Buffalo) and Dr. Zhi-Hua Zhou (Nanjing) for their significant contributions to the field of intelligent biological medicine.
doi:10.1186/1471-2164-11-S3-I1
PMCID: PMC2999338  PMID: 21143775
4.  Guidelines, Editors, Pharma And The Biological Paradigm Shift 
Mens Sana Monographs  2007;5(1):27-30.
Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.
There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.
Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.
A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.
Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a relatively recent survey of 2002, it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. There is a strong case for making CPGs based not just on effectivity but cost effectivity. The various ramifications of this need to be spelt out. Work of bodies like the Appraisal of Guidelines Research and Evaluation (AGREE) Collaboration and Guidelines Advisory Committee (GAC) are also worth a close look.
Even the actions of Foundations that work for disease amelioration have come under scrutiny. The process of setting up ‘Best Practices’ Guidelines for interactions between the pharmaceutical industry and clinicians has already begun and can have important consequences for patient care. Similarly, Good Publication Practice (GPP) for pharmaceutical companies have also been set up aimed at improving the behaviour of drug companies while reporting drug trials
The rapidly increasing trend toward influence and control by industry has become a concern for many. It is of such importance that the Association of American Medical Colleges has issued two relatively new documents - one, in 2001, on how to deal with individual conflicts of interest; and the other, in 2002, on how to deal with institutional conflicts of interest in the conduct of clinical research. Academic Medical Centers (AMCs), as also medical education and research institutions at other places, have to adopt means that minimize their conflicts of interest.
Both medical associations and research journal editors are getting concerned with individual and institutional conflicts of interest in the conduct of clinical research and documents are now available which address these issues. The 2001 ICMJE revision calls for full disclosure of the sponsor's role in research, as well as assurance that the investigators are independent of the sponsor, are fully accountable for the design and conduct of the trial, have independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.
There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a ‘gold standard’ or which that player thinks has still some ‘juice’ left.
Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.
An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.
We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.
The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady techniques of the upstart new entrant. Secrecy of marketing/sales tactics, of the process of manufacture, of other strategies and plans of business expansion, of strategies to tackle competition are fine business tactics. But it is critical that secrecy as a tactic not extend to reporting of research findings, especially those contrary to one's product.
Pharma has no option but to make a quality product, do comprehensive adverse reaction profiles, and market it only if it passes both tests.
Why does pharma adopt questionable tactics? The reasons are essentially two:
What with all the constraints, a drug comes to the pharmacy after huge investments. There are crippling overheads and infrastructure costs to be recovered. And there are massive profit margins to be maintained. If these were to be dependent only on genuine drug discoveries, that would be taking too great a risk.Industry players have to strike the right balance between profit making and credibility. In profit making, the marketing champions play their role. In credibility ratings, researchers and paid spokes-persons play their role. All is hunky dory till marketing is based on credibility. When there is nothing available to make for credibility, something is projected as one and marketing carried out, in the calculated hope that profits can accrue, since profit making must continue endlessly. That is what makes pharma adopt even questionable means to make profits.
Essentially, there are four types of drugs. First, drugs that work and have minimal side-effects; second, drugs which work but have serious side-effects; third, drugs that do not work and have minimal side-effects; and fourth, drugs which work minimally but have serious side-effects. It is the second and fourth types that create major hassles for industry. Often, industry may try to project the fourth type as the second to escape censure.
The major cat and mouse game being played by conscientious researchers is in exposing the third and fourth for what they are and not allowing industry to palm them off as the first and second type respectively. The other major game is in preventing the second type from being projected as the first. The third type are essentially harmless, so they attract censure all right and some merriment at the antics to market them. But they escape anything more than a light rap on the knuckles, except when they are projected as the first type.
What is necessary for industry captains and long-term players is to realise:
Their major propelling force can only be producing the first type. 2. They accept the second type only till they can lay their hands on the first. 3. The third type can be occasionally played around with to shore up profits, but never by projecting them as the first type. 4. The fourth type are the laggards, real threat to credibility and therefore do not deserve any market hype or promotion.
In finding out why most pharma indulges in questionable tactics, we are lead to some interesting solutions to prevent such tactics with the least amount of hassles for all concerned, even as both profits and credibility are kept intact.
doi:10.4103/0973-1229.32176
PMCID: PMC3192391  PMID: 22058616
Academia; Pharmaceutical Industry; Clinical Practice Guidelines; Best Practice Guidelines; Academic Medical Centers; Medical Associations; Research Journals; Clinical Research; Public Welfare; Pharma Image; Corporate Welfare; Biological Psychiatry; Law Suits Against Industry
5.  Measurement Issues in the Use of Cognitive Neuroscience Tasks in Drug Development for Impaired Cognition in Schizophrenia: A Report of the Second Consensus Building Conference of the CNTRICS Initiative 
Schizophrenia Bulletin  2008;34(4):613-618.
This overview describes the goals and objectives of the second conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This second conference was informed by a series of online surveys and brought together basic and clinical scientists from academia and industry to address the concerns central to each field of research. Our goal was to develop recommendations for future research addressing the psychometric and practical challenges involved in translating paradigms from cognitive neuroscience into tasks that are feasible for use in the treatment discovery and development process. In this overview article, we describe the series of talks that were presentations at the conference. This article serves as an introduction to the set of articles included in this special issue that provide overviews and discussions of the issues raised and the recommendations made in these talks and in the subsequent discussions at the meeting. In addition, we describe the online surveys conducted in the month before the conference that were used to obtain suggestions from the field as to important task selection criteria and to generate initial benchmark goals for psychometric development for cognitive neuroscience tasks.
doi:10.1093/schbul/sbn037
PMCID: PMC2632448  PMID: 18499705
treatment; translation; pharmacology
6.  Vascular Contributions to Cognitive Impairment and Dementia 
Background and Purpose
This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment.
Methods
Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee.
Results
The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury—not solely stroke—ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular unit and mechanisms regulating cerebral blood flow are likely to be important components of the pathophysiological processes underlying VCI. Cerebral amyloid angiopathy is emerging as an important marker of risk for Alzheimer disease, microinfarction, microhemorrhage and macrohemorrhage of the brain, and VCI. The neuropathology of cognitive impairment in later life is often a mixture of Alzheimer disease and microvascular brain damage, which may overlap and synergize to heighten the risk of cognitive impairment. In this regard, magnetic resonance imaging and other neuroimaging techniques play an important role in the definition and detection of VCI and provide evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common. In many cases, risk markers for VCI are the same as traditional risk factors for stroke. These risks may include but are not limited to atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia. Furthermore, these same vascular risk factors may be risk markers for Alzheimer disease. Carotid intimal-medial thickness and arterial stiffness are emerging as markers of arterial aging and may serve as risk markers for VCI. Currently, no specific treatments for VCI have been approved by the US Food and Drug Administration. However, detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of VCI, even in older people.
Conclusions
Vascular contributions to cognitive impairment and dementia are important. Understanding of VCI has evolved substantially in recent years, based on preclinical, neuropathologic, neuroimaging, physiological, and epidemiological studies. Transdisciplinary, translational, and transactional approaches are recommended to further our understanding of this entity and to better characterize its neuropsychological profile. There is a need for prospective, quantitative, clinical-pathological-neuroimaging studies to improve knowledge of the pathological basis of neuroimaging change and the complex interplay between vascular and Alzheimer disease pathologies in the evolution of clinical VCI and Alzheimer disease. Long-term vascular risk marker interventional studies beginning as early as midlife may be required to prevent or postpone the onset of VCI and Alzheimer disease. Studies of intensive reduction of vascular risk factors in high-risk groups are another important avenue of research.
doi:10.1161/STR.0b013e3182299496
PMCID: PMC3778669  PMID: 21778438
AHA Scientific Statements; vascular dementia; Alzheimer disease; risk factors; prevention; treatment
7.  Diabetes and oral disease: implications for health professionals 
“Diabetes and Oral Disease: Implications for Health Professionals” was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the inter-professional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them and ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event.
doi:10.1111/j.1749-6632.2011.06460.x
PMCID: PMC3429365  PMID: 22409777
diabetes; oral disease; meeting report
8.  ISMB/ECCB 2009 Stockholm 
Bioinformatics  2009;25(12):1570-1573.
The International Society for Computational Biology (ISCB; http://www.iscb.org) presents the Seventeenth Annual International Conference on Intelligent Systems for Molecular Biology (ISMB), organized jointly with the Eighth Annual European Conference on Computational Biology (ECCB; http://bioinf.mpi-inf.mpg.de/conferences/eccb/eccb.htm), in Stockholm, Sweden, 27 June to 2 July 2009. The organizers are putting the finishing touches on the year's premier computational biology conference, with an expected attendance of 1400 computer scientists, mathematicians, statisticians, biologists and scientists from other disciplines related to and reliant on this multi-disciplinary science. ISMB/ECCB 2009 (http://www.iscb.org/ismbeccb2009/) follows the framework introduced at the ISMB/ECCB 2007 (http://www.iscb.org/ismbeccb2007/) in Vienna, and further refined at the ISMB 2008 (http://www.iscb.org/ismb2008/) in Toronto; a framework developed to specifically encourage increased participation from often under-represented disciplines at conferences on computational biology. During the main ISMB conference dates of 29 June to 2 July, keynote talks from highly regarded scientists, including ISCB Award winners, are the featured presentations that bring all attendees together twice a day. The remainder of each day offers a carefully balanced selection of parallel sessions to choose from: proceedings papers, special sessions on emerging topics, highlights of the past year's published research, special interest group meetings, technology demonstrations, workshops and several unique sessions of value to the broad audience of students, faculty and industry researchers. Several hundred posters displayed for the duration of the conference has become a standard of the ISMB and ECCB conference series, and an extensive commercial exhibition showcases the latest bioinformatics publications, software, hardware and services available on the market today. The main conference is preceded by 2 days of Special Interest Group (SIG) and Satellite meetings running in parallel to the fifth Student Council Symposium on 27 June, and in parallel to Tutorials on 28 June. All scientific sessions take place at the Stockholmsmässan/Stockholm International Fairs conference and exposition facility.
Contact: bj@iscb.org
doi:10.1093/bioinformatics/btp280
PMCID: PMC2687994  PMID: 19447790
9.  Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research 
BMC Genomics  2008;9(Suppl 2):I1.
Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA.
doi:10.1186/1471-2164-9-S2-I1
PMCID: PMC3226104  PMID: 18831773
10.  Tobacco Company Efforts to Influence the Food and Drug Administration-Commissioned Institute of Medicine Report Clearing the Smoke: An Analysis of Documents Released through Litigation 
PLoS Medicine  2013;10(5):e1001450.
Stanton Glantz and colleagues investigate efforts by tobacco companies to influence Clearing the Smoke, a 2001 Institute of Medicine report on harm reduction tobacco products.
Please see later in the article for the Editors' Summary
Background
Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco “harm reduction,” leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report.
Methods and Findings
We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes (“substantial equivalence”) without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act.
Conclusions
Tobacco companies strategically interacted with the IOM to win several favored scientific and regulatory recommendations.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Up to half of tobacco users will die of cancer, lung disease, heart disease, stroke, or another tobacco-related disease. Cigarettes and other tobacco products cause disease because they expose their users to nicotine and numerous other toxic chemicals. Tobacco companies have been working to develop a “safe” cigarette for more than half a century. Initially, their attention focused on cigarettes that produced lower tar and nicotine yields in machine-smoking tests. These products were perceived as “safer” products by the public and scientists for many years, but it is now known that the use of low-yield cigarettes can actually expose smokers to higher levels of toxins than standard cigarettes. More recently, the tobacco companies have developed other products (for example, products that heat aerosols of nicotine, rather than burning the tobacco) that claim to reduce harm and the risk of tobacco-related disease, but they can only market these modified risk tobacco products in the US after obtaining Food and Drug Administration (FDA) approval. In 1999, the FDA commissioned the US Institute of Medicine (IOM, an influential source of independent expert advice on medical issues) to assess the science base for tobacco “harm reduction.” In 2001, the IOM published its report Clearing the Smoke: Assessing the Science Base for Tobacco Harm and Reduction, which, although controversial, set the tone for the development and regulation of tobacco products in the US, particularly those claiming to be less dangerous, in subsequent years.
Why Was This Study Done?
Tobacco companies have a long history of working to shape scientific discussions and agendas. For example, they have produced research results designed to “create controversy” about the dangers of smoking and secondhand smoke. In this study, the researchers investigate how tobacco companies organized to try to influence the IOM committee that prepared the Clearing the Smoke report on modified risk tobacco products by analyzing tobacco industry and IOM documents.
What Did the Researchers Do and Find?
The researchers searched the Legacy Tobacco Documents Library (a collection of internal tobacco industry documents released as a result of US litigation cases) for documents outlining how tobacco companies tried to influence the IOM Committee to Assess the Science Base for Tobacco Harm Reduction and created a timeline of events from the 1,000 or so documents they retrieved. They confirmed and supplemented this timeline using information in 80 files that detailed written interactions between the tobacco companies and the IOM committee, which they obtained through a public records access request. Analysis of these documents indicates that the tobacco companies considered the IOM report to have important regulatory implications, that they developed and implemented strategies with consulting and legal firms to access the IOM proceedings, and that tobacco company lawyers, consultants, and regulatory staff shaped presentations to the IOM committee by company scientists on various aspects of tobacco harm reduction products. The analysis also shows that tobacco companies were pleased with the final report, particularly its recommendation that tobacco products can be marketed with exposure or risk reduction claims provided the products substantially reduce exposure and provided the behavioral and health consequences of these products are determined in post-marketing surveillance and epidemiological studies (“tiered testing”) and its recommendation that, provided no claim of reduced exposure or risk is made, new products comparable to existing conventional cigarettes (“substantial equivalence”) can be marketed without prior regulatory approval.
What Do These Findings Mean?
These findings suggest that tobacco companies used their legal and regulatory staff to access the IOM committee that advised the FDA on modified risk tobacco products and that they used this access to deliver specific, carefully formulated messages designed to serve their business interests. Although these findings provide no evidence that the efforts of tobacco companies influenced the IOM committee in any way, they show that the companies were satisfied with the final IOM report and its recommendations, some of which have policy implications that continue to reverberate today. The researchers therefore call for the FDA and other regulatory bodies to remember that they are dealing with companies with a long history of intentionally misleading the public when assessing the information presented by tobacco companies as part of the regulatory process and to actively protect their public-health policies from the commercial interests of the tobacco industry.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001450.
This study is further discussed in a PLOS Medicine Perspective by Thomas Novotny
The World Health Organization provides information about the dangers of tobacco (in several languages); for information about the tobacco industry's influence on policy, see the 2009 World Health Organization report Tobacco interference with tobacco control
A PLOS Medicine Research Article by Heide Weishaar and colleagues describes tobacco company efforts to undermine the Framework Convention on Tobacco Control, an international instrument for tobacco control
Wikipedia has a page on tobacco harm reduction (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The IOM report Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction is available to read online
The Legacy Tobacco Documents Library is a public, searchable database of tobacco company internal documents detailing their advertising, manufacturing, marketing, sales, and scientific activities
The University of California, San Francisco Center for Tobacco Control Research and Education is the focal point for University of California, San Francisco (UCSF) scientists in disciplines ranging from the molecular biology of nicotine addiction through political science who combine their efforts to eradicate the use of tobacco and tobacco-induced cancer and other diseases worldwide
SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking
Smokefree.gov, from the US National Cancer Institute, offers online tools and resources to help people quit smoking
doi:10.1371/journal.pmed.1001450
PMCID: PMC3665841  PMID: 23723740
11.  Implementing the 2009 Institute of Medicine recommendations on resident physician work hours, supervision, and safety 
Long working hours and sleep deprivation have been a facet of physician training in the US since the advent of the modern residency system. However, the scientific evidence linking fatigue with deficits in human performance, accidents and errors in industries from aeronautics to medicine, nuclear power, and transportation has mounted over the last 40 years. This evidence has also spawned regulations to help ensure public safety across safety-sensitive industries, with the notable exception of medicine.
In late 2007, at the behest of the US Congress, the Institute of Medicine embarked on a year-long examination of the scientific evidence linking resident physician sleep deprivation with clinical performance deficits and medical errors. The Institute of Medicine’s report, entitled “Resident duty hours: Enhancing sleep, supervision and safety”, published in January 2009, recommended new limits on resident physician work hours and workload, increased supervision, a heightened focus on resident physician safety, training in structured handovers and quality improvement, more rigorous external oversight of work hours and other aspects of residency training, and the identification of expanded funding sources necessary to implement the recommended reforms successfully and protect the public and resident physicians themselves from preventable harm.
Given that resident physicians comprise almost a quarter of all physicians who work in hospitals, and that taxpayers, through Medicare and Medicaid, fund graduate medical education, the public has a deep investment in physician training. Patients expect to receive safe, high-quality care in the nation’s teaching hospitals. Because it is their safety that is at issue, their voices should be central in policy decisions affecting patient safety. It is likewise important to integrate the perspectives of resident physicians, policy makers, and other constituencies in designing new policies. However, since its release, discussion of the Institute of Medicine report has been largely confined to the medical education community, led by the Accreditation Council for Graduate Medical Education (ACGME).
To begin gathering these perspectives and developing a plan to implement safer work hours for resident physicians, a conference entitled “Enhancing sleep, supervision and safety: What will it take to implement the Institute of Medicine recommendations?” was held at Harvard Medical School on June 17–18, 2010. This White Paper is a product of a diverse group of 26 representative stakeholders bringing relevant new information and innovative practices to bear on a critical patient safety problem. Given that our conference included experts from across disciplines with diverse perspectives and interests, not every recommendation was endorsed by each invited conference participant. However, every recommendation made here was endorsed by the majority of the group, and many were endorsed unanimously. Conference members participated in the process, reviewed the final product, and provided input before publication. Participants provided their individual perspectives, which do not necessarily represent the formal views of any organization.
In September 2010 the ACGME issued new rules to go into effect on July 1, 2011. Unfortunately, they stop considerably short of the Institute of Medicine’s recommendations and those endorsed by this conference. In particular, the ACGME only applied the limitation of 16 hours to first-year resident physicans. Thus, it is clear that policymakers, hospital administrators, and residency program directors who wish to implement safer health care systems must go far beyond what the ACGME will require. We hope this White Paper will serve as a guide and provide encouragement for that effort.
Resident physician workload and supervision
By the end of training, a resident physician should be able to practice independently. Yet much of resident physicians’ time is dominated by tasks with little educational value. The caseload can be so great that inadequate reflective time is left for learning based on clinical experiences. In addition, supervision is often vaguely defined and discontinuous. Medical malpractice data indicate that resident physicians are frequently named in lawsuits, most often for lack of supervision. The recommendations are: The ACGME should adjust resident physicians workload requirements to optimize educational value. Resident physicians as well as faculty should be involved in work redesign that eliminates nonessential and noneducational activity from resident physician dutiesMechanisms should be developed for identifying in real time when a resident physician’s workload is excessive, and processes developed to activate additional providersTeamwork should be actively encouraged in delivery of patient care. Historically, much of medical training has focused on individual knowledge, skills, and responsibility. As health care delivery has become more complex, it will be essential to train resident and attending physicians in effective teamwork that emphasizes collective responsibility for patient care and recognizes the signs, both individual and systemic, of a schedule and working conditions that are too demanding to be safeHospitals should embrace the opportunities that resident physician training redesign offers. Hospitals should recognize and act on the potential benefits of work redesign, eg, increased efficiency, reduced costs, improved quality of care, and resident physician and attending job satisfactionAttending physicians should supervise all hospital admissions. Resident physicians should directly discuss all admissions with attending physicians. Attending physicians should be both cognizant of and have input into the care patients are to receive upon admission to the hospitalInhouse supervision should be required for all critical care services, including emergency rooms, intensive care units, and trauma services. Resident physicians should not be left unsupervised to care for critically ill patients. In settings in which the acuity is high, physicians who have completed residency should provide direct supervision for resident physicians. Supervising physicians should always be physically in the hospital for supervision of resident physicians who care for critically ill patientsThe ACGME should explicitly define “good” supervision by specialty and by year of training. Explicit requirements for intensity and level of training for supervision of specific clinical scenarios should be providedCenters for Medicare and Medicaid Services (CMS) should use graduate medical education funding to provide incentives to programs with proven, effective levels of supervision. Although this action would require federal legislation, reimbursement rules would help to ensure that hospitals pay attention to the importance of good supervision and require it from their training programs
Resident physician work hours
Although the IOM “Sleep, supervision and safety” report provides a comprehensive review and discussion of all aspects of graduate medical education training, the report’s focal point is its recommendations regarding the hours that resident physicians are currently required to work. A considerable body of scientific evidence, much of it cited by the Institute of Medicine report, describes deteriorating performance in fatigued humans, as well as specific studies on resident physician fatigue and preventable medical errors.
The question before this conference was what work redesign and cultural changes are needed to reform work hours as recommended by the Institute of Medicine’s evidence-based report? Extensive scientific data demonstrate that shifts exceeding 12–16 hours without sleep are unsafe. Several principles should be followed in efforts to reduce consecutive hours below this level and achieve safer work schedules. The recommendations are: Limit resident physician work hours to 12–16 hour maximum shiftsA minimum of 10 hours off duty should be scheduled between shiftsResident physician input into work redesign should be actively solicitedSchedules should be designed that adhere to principles of sleep and circadian science; this includes careful consideration of the effects of multiple consecutive night shifts, and provision of adequate time off after night work, as specified in the IOM reportResident physicians should not be scheduled up to the maximum permissible limits; emergencies frequently occur that require resident physicians to stay longer than their scheduled shifts, and this should be anticipated in scheduling resident physicians’ work shiftsHospitals should anticipate the need for iterative improvement as new schedules are initiated; be prepared to learn from the initial phase-in, and change the plan as neededAs resident physician work hours are redesigned, attending physicians should also be considered; a potential consequence of resident physician work hour reduction and increased supervisory requirements may be an increase in work for attending physicians; this should be carefully monitored, and adjustments to attending physician work schedules made as needed to prevent unsafe work hours or working conditions for this group“Home call” should be brought under the overall limits of working hours; work load and hours should be monitored in each residency program to ensure that resident physicians and fellows on home call are getting sufficient sleepMedicare funding for graduate medical education in each hospital should be linked with adherence to the Institute of Medicine limits on resident physician work hours
Moonlighting by resident physicians
The Institute of Medicine report recommended including external as well as internal moonlighting in working hour limits. The recommendation is: All moonlighting work hours should be included in the ACGME working hour limits and actively monitored. Hospitals should formalize a moonlighting policy and establish systems for actively monitoring resident physician moonlighting
Safety of resident physicians
The “Sleep, supervision and safety” report also addresses fatigue-related harm done to resident physicians themselves. The report focuses on two main sources of physical injury to resident physicians impaired by fatigue, ie, needle-stick exposure to blood-borne pathogens and motor vehicle crashes. Providing safe transportation home for resident physicians is a logistical and financial challenge for hospitals. Educating physicians at all levels on the dangers of fatigue is clearly required to change driving behavior so that safe hospital-funded transport home is used effectively. Fatigue-related injury prevention (including not driving while drowsy) should be taught in medical school and during residency, and reinforced with attending physicians; hospitals and residency programs must be informed that resident physicians’ ability to judge their own level of impairment is impaired when they are sleep deprived; hence, leaving decisions about the capacity to drive to impaired resident physicians is not recommendedHospitals should provide transportation to all resident physicians who report feeling too tired to drive safely; in addition, although consecutive work should not exceed 16 hours, hospitals should provide transportation for all resident physicians who, because of unforeseen reasons or emergencies, work for longer than consecutive 24 hours; transportation under these circumstances should be automatically provided to house staff, and should not rely on self-identification or request
Training in effective handovers and quality improvement
Handover practice for resident physicians, attendings, and other health care providers has long been identified as a weak link in patient safety throughout health care settings. Policies to improve handovers of care must be tailored to fit the appropriate clinical scenario, recognizing that information overload can also be a problem. At the heart of improving handovers is the organizational effort to improve quality, an effort in which resident physicians have typically been insufficiently engaged. The recommendations are: Hospitals should train attending and resident physicians in effective handovers of careHospitals should create uniform processes for handovers that are tailored to meet each clinical setting; all handovers should be done verbally and face-to-face, but should also utilize written toolsWhen possible, hospitals should integrate hand-over tools into their electronic medical records (EMR) systems; these systems should be standardized to the extent possible across residency programs in a hospital, but may be tailored to the needs of specific programs and services; federal government should help subsidize adoption of electronic medical records by hospitals to improve signoutWhen feasible, handovers should be a team effort including nurses, patients, and familiesHospitals should include residents in their quality improvement and patient safety efforts; the ACGME should specify in their core competency requirements that resident physicians work on quality improvement projects; likewise, the Joint Commission should require that resident physicians be included in quality improvement and patient safety programs at teaching hospitals; hospital administrators and residency program directors should create opportunities for resident physicians to become involved in ongoing quality improvement projects and root cause analysis teams; feedback on successful quality improvement interventions should be shared with resident physicians and broadly disseminatedQuality improvement/patient safety concepts should be integral to the medical school curriculum; medical school deans should elevate the topics of patient safety, quality improvement, and teamwork; these concepts should be integrated throughout the medical school curriculum and reinforced throughout residency; mastery of these concepts by medical students should be tested on the United States Medical Licensing Examination (USMLE) stepsFederal government should support involvement of resident physicians in quality improvement efforts; initiatives to improve quality by including resident physicians in quality improvement projects should be financially supported by the Department of Health and Human Services
Monitoring and oversight of the ACGME
While the ACGME is a key stakeholder in residency training, external voices are essential to ensure that public interests are heard in the development and monitoring of standards. Consequently, the Institute of Medicine report recommended external oversight and monitoring through the Joint Commission and Centers for Medicare and Medicaid Services (CMS). The recommendations are: Make comprehensive fatigue management a Joint Commission National Patient Safety Goal; fatigue is a safety concern not only for resident physicians, but also for nurses, attending physicians, and other health care workers; the Joint Commission should seek to ensure that all health care workers, not just resident physicians, are working as safely as possibleFederal government, including the Centers for Medicare and Medicaid Services and the Agency for Healthcare Research and Quality, should encourage development of comprehensive fatigue management programs which all health systems would eventually be required to implementMake ACGME compliance with working hours a “ condition of participation” for reimbursement of direct and indirect graduate medical education costs; financial incentives will greatly increase the adoption of and compliance with ACGME standards
Future financial support for implementation
The Institute of Medicine’s report estimates that $1.7 billion (in 2008 dollars) would be needed to implement its recommendations. Twenty-five percent of that amount ($376 million) will be required just to bring hospitals into compliance with the existing 2003 ACGME rules. Downstream savings to the health care system could potentially result from safer care, but these benefits typically do not accrue to hospitals and residency programs, who have been asked historically to bear the burden of residency reform costs. The recommendations are: The Institute of Medicine should convene a panel of stakeholders, including private and public funders of health care and graduate medical education, to lay down the concrete steps necessary to identify and allocate the resources needed to implement the recommendations contained in the IOM “Resident duty hours: Enhancing sleep, supervision and safety” report. Conference participants suggested several approaches to engage public and private support for this initiativeEfforts to find additional funding to implement the Institute of Medicine recommendations should focus more broadly on patient safety and health care delivery reform; policy efforts focused narrowly upon resident physician work hours are less likely to succeed than broad patient safety initiatives that include residency redesign as a key componentHospitals should view the Institute of Medicine recommendations as an opportunity to begin resident physician work redesign projects as the core of a business model that embraces safety and ultimately saves resourcesBoth the Secretary of Health and Human Services and the Director of the Centers for Medicare and Medicaid Services should take the Institute of Medicine recommendations into consideration when promulgating rules for innovation grantsThe National Health Care Workforce Commission should consider the Institute of Medicine recommendations when analyzing the nation’s physician workforce needs
Recommendations for future research
Conference participants concurred that convening the stakeholders and agreeing on a research agenda was key. Some observed that some sectors within the medical education community have been reluctant to act on the data. Several logical funders for future research were identified. But above all agencies, Centers for Medicare and Medicaid Services is the only stakeholder that funds graduate medical education upstream and will reap savings downstream if preventable medical errors are reduced as a result of reform of resident physician work hours.
doi:10.2147/NSS.S19649
PMCID: PMC3630963  PMID: 23616719
resident; hospital; working hours; safety
12.  The developing brain and the environment: an introduction. 
Environmental Health Perspectives  2000;108(Suppl 3):373-374.
mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester conference came from both public and private sources. The National Institute of Environmental Health Sciences (NIEHS), the National Institute of Child Health and Human Development, and the EPA represented the federal government. The conference also received grants from several foundations: the Jennifer Altman Foundation, the Heinz Family Foundation, the National Alliance for Autism Research, the Violence Research Foundation, the Wacker Foundation, and the Winslow Foundation. The second of these conferences helped launch a new Center for Children's Health and the Environment at the Mount Sinai School of Medicine. It was held in New York City on 24-25 May 1999, and was convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference title was Environmental Influences on Children: Brain, Development, and Behavior. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its (italic)Handbook of Pediatric Environmental Health (/italic)((italic)17(/italic)), the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline.
PMCID: PMC1637828  PMID: 10852830
13.  Advancing drug discovery for schizophrenia 
Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia.
doi:10.1111/j.1749-6632.2011.06216.x
PMCID: PMC3787879  PMID: 22032400
schizophrenia; genetics; GWAS; neuronal function; small molecules; therapeutics
14.  The need for academic generalists 
Molecular Biology of the Cell  2011;22(11):1807-1809.
Academia should be willing to shoulder some of the responsibility for the current dearth of new therapeutic drugs. Our research funding is predicated on the assumption that it will bring value to society, but our emphasis on scientific specialization hinders our ability to add value when a broader vision is required. A solution is the creation of an academy of science generalists motivated to bring together clinical and basic scientists, academia and the private sector, government legislators and industry. A small investment in academic generalists could yield benefits far beyond its modest cost.
doi:10.1091/mbc.E11-03-0187
PMCID: PMC3103397  PMID: 21622898
15.  The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception 
The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities whereas MRI measures of change were shown to be the most efficient outcome measures; 6) the confirmation of the AD risk loci CLU, CR1 and PICALM and the identification of novel candidate risk loci; 7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia and Australia; 8) understanding the biology and pathobiology of normal aging, MCI and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD thereby advancing efforts to find disease modifying drugs for AD; and 9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a two year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI2) in October, 2010 through to 2016, with enrollment of an additional 550 participants.
doi:10.1016/j.jalz.2011.09.172
PMCID: PMC3329969  PMID: 22047634
16.  The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception 
The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants.
doi:10.1016/j.jalz.2013.05.1769
PMCID: PMC4108198  PMID: 23932184
Alzheimer's disease; Mild cognitive impairment; Amyloid; Tau; Biomarker
17.  “A Good Personal Scientific Relationship”: Philip Morris Scientists and the Chulabhorn Research Institute, Bangkok 
PLoS Medicine  2008;5(12):e238.
Background
This paper examines the efforts of consultants affiliated with Philip Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005.
Methods and Findings
This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships.
Conclusions
The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently awarded status as a WHO Collaborating Centre. Since the network of WHO Collaborating Centres rests on the principle of “using national institutions for international purposes,” the documents presented below suggest that more rigorous safeguards are required to ensure that such use advances public health goals rather than the objectives of transnational corporations.
Jeff Collin and Ross MacKenzie analyze tobacco industry documents and find that Philip Morris consultants were able to gain access to a Thai research institute that is a WHO Collaborating Centre.
Editors' Summary
Background.
Tobacco use kills 5.4 million people a year (one person every six seconds) and accounts for one in ten adult deaths worldwide. Globally, the use of tobacco is on the rise, especially in developing countries, which have become a major target for tobacco industry marketing. The tobacco industry has worked hard to try and influence public perceptions about the risks of smoking and the risk of inhaling secondhand smoke (passive smoking). The industry has used a variety of tactics to downplay the health hazards of smoking or inhaling secondhand smoke—two examples are publishing articles casting doubts about the health hazards of tobacco and funding research that is biased toward giving pro-industry results. Another tactic is for tobacco industry consultants to try and gain entry to universities and other academic centers to see if they can influence research and teaching activities.
Why Was This Study Done?
The researchers were concerned that consultants from the tobacco company Philip Morris had gained access to an academic research center in Thailand called the Chulabhorn Research Institute (CRI). The CRI is an internationally renowned teaching institution for a variety of scientific disciplines, including environmental toxicology (the study of how chemicals in the environment, such as tobacco smoke, can affect human health), biomedicine, and biotechnology. The institute has secured funding from the Thai government, the Association of Southeast Nations and the United Nations Development Programme. In 2005 the institute's environmental toxicology unit was designated a World Health Organization (WHO) Collaborating Centre. WHO Collaborating Centres are “institutions such as research institutes, parts of universities or academies, that are designated by the Director-General of the WHO to carry out activities in support of the WHO's programs” (http://www.who.int/collaboratingcentres/en/). The researchers were concerned that Philip Morris consultants had been able to develop relationships with the CRI to help advance the company's interests.
What Did the Researchers Do and Find?
The researchers analyzed previously confidential tobacco industry documents that were made publicly available online following litigation in the United States. They searched two online collections of industry documents—the Legacy Tobacco Documents Library and Tobacco Documents Online—as well as the online collections operated by US-based tobacco companies. They found that consultants to Philip Morris were able to gain access to the scientific community in Thailand. A Philip Morris scientist named Roger Walk was able to establish close connections to the CRI, and he used these connections to influence research and teaching activities at the CRI on environmental toxicology. Walk was also able to build relationships with government officials and scientists in Thailand to help advance the interests of Philip Morris in the country and across Asia.
What Do these Findings Mean?
This study provides evidence that the tobacco industry has established close links with a research institute in Thailand that collaborates with the WHO, and has been able to influence the institute's teaching curriculum and research. Such links are of great concern to the public health community, which is working hard to reduce deaths and disease due to tobacco. These links raise the possibility that the tobacco industry is managing to influence medical research and teaching at academic institutions. The WHO has stated that a firewall is in place between itself and the tobacco industry—but the study authors argue, based on their findings, that “this firewall is not impenetrable.” The study findings, they conclude, highlight a challenge posed to international tobacco control efforts, especially with respect to Article 5.3 of an international treaty called the WHO Framework Convention on Tobacco Control; Article 5.3 addresses the need to protect public health policies from the vested interests of the tobacco industry. The authors say that better safeguards must be put in place to prevent tobacco companies from thwarting public health goals.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050238.
The Legacy Tobacco Documents Library contains over 9.7 million documents created by tobacco companies
Tobacco Documents Online contains over 4 million tobacco industry documents
Over 900 WHO Collaborating Centres are at work in 99 Member States on many health disciplines
The WHO held an inquiry in 2000 into possible tobacco industry influence over the organization (and over other UN agencies), and has published its recommendations in response to this inquiry
The WHO Framework Convention on Tobacco Control is an international treaty on controlling tobacco
doi:10.1371/journal.pmed.0050238
PMCID: PMC2605886  PMID: 19108600
18.  Mary S. Easton Center of Alzheimer’s Disease Research at UCLA: Advancing the Therapeutic Imperative 
The Mary S. Easton Center for Alzheimer’s Disease Research (UCLA-Easton Alzheimer’s Center) is committed to the “therapeutic imperative” and is devoted to finding new treatments for Alzheimer’s disease (AD) and to developing technologies (biomarkers) to advance that goal. The UCLA-Easton Alzheimer’s Center has a continuum of research and research-related activities including basic/foundational studies of peptide interactions; translational studies in transgenic animals and other animal models of AD; clinical research to define the phenotype of AD, characterize familial AD, develop biomarkers, and advance clinical trials; health services and outcomes research; and active education, dissemination, and recruitment activities. The UCLA-Easton Alzheimer’s Center is supported by the National Institutes on Aging, the State of California, and generous donors who share our commitment to developing new therapies for AD. The naming donor (Jim Easton) provided substantial funds to endow the center and to support projects in AD drug discovery and biomarker development. The Sidell-Kagan Foundation supports the Katherine and Benjamin Kagan Alzheimer’s Treatment Development Program, and the Deane F. Johnson Alzheimer’s Research Foundation supports the Deane F. Johnson Center for Neurotherapeutics at UCLA. The John Douglas French Alzheimer’s Research Foundation provides grants to junior investigators in critical periods of their academic development. The UCLA-Easton Alzheimer’s Center partners with community organizations including the Alzheimer’s Association California Southland Chapter and the Leeza Gibbons memory Foundation. Collaboration with pharmaceutical companies, biotechnology companies, and device companies is critical to developing new therapeutics for AD and these collaborations are embraced in the mission of the UCLA-Easton Alzheimer’s Center. The Center supports excellent senior investigators and serves as an incubator for new scientists, agents, models, technologies and concepts that will significantly influence the future of AD treatment and AD research.
doi:10.3233/JAD-2010-1286
PMCID: PMC2855886  PMID: 20110588
19.  Eurocan plus report: feasibility study for coordination of national cancer research activities 
Summary
The EUROCAN+PLUS Project, called for by the European Parliament, was launched in October 2005 as a feasibility study for coordination of national cancer research activities in Europe. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people, the largest Europe–wide consultation ever conducted in the field of cancer research.
Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
It is essential to include the patients’ voice in the establishment of priority areas in cancer research at the present time. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community is evident. A top priority should be the development of translational research (in its widest form), leading to the development of effective and innovative cancer treatments and preventive strategies. Translational research ranges from bench–to–bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
The EUROCAN+PLUS Project recommends the creation of a small, permanent and independent European Cancer Initiative (ECI). This should be a model structure and was widely supported at both General Assemblies of the project. The ECI should assume responsibility for stimulating innovative cancer research and facilitating processes, becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ organizations, European institutions, Member States, industry and small and medium enterprises (SMEs), putting into practice solutions aimed at alleviating barriers to collaboration and coordination of cancer research activities in the European Union, and dealing with legal and regulatory issues. The development of an effective ECI will require time, but this entity should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co–operation between comprehensive cancer centres and basic research laboratories throughout Europe and (3) networking between funding bodies at the European level.
The European Parliament and its instruments have had a major influence in cancer control in Europe, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
Executive Summary
Cancer is one of the biggest public health crises facing Europe in the 21st century—one for which Europe is currently not prepared nor preparing itself. Cancer is a major cause of death in Europe with two million casualties and three million new cases diagnosed annually, and the situation is set to worsen as the population ages.
These facts led the European Parliament, through the Research Directorate-General of the European Commission, to call for initiatives for better coordination of cancer research efforts in the European Union. The EUROCAN+PLUS Project was launched in October 2005 as a feasibility study for coordination of national cancer research activities. Over the course of the next two years, the Project process organized over 60 large meetings and countless smaller meetings that gathered in total over a thousand people. In this respect, the Project became the largest Europe-wide consultation ever conducted in the field of cancer research, implicating researchers, cancer centres and hospitals, administrators, healthcare professionals, funding agencies, industry, patients’ organizations and patients.
The Project first identified barriers impeding research and collaboration in research in Europe. Despite a strong tradition in biomedical science in Europe, fragmentation and lack of sustainability remain the formidable challenges for implementing innovative cancer research and cancer care improvement. There is an enormous duplication of research effort in the Member States, which wastes time, wastes money and severely limits the total intellectual concentration on the wide cancer problem. There is a striking lack of communication between some of the biggest actors on the European scene, and there are palpable tensions between funders and those researchers seeking funds.
In addition, there is a shortage of leadership, a multiplicity of institutions each focusing on its own agenda, sub–optimal contact with industry, inadequate training, non–existent career paths, low personnel mobility in research especially among clinicians and inefficient funding—all conspiring against efficient collaboration in cancer care and research. European cancer research today does not have a functional translational research continuum, that is the process that exploits biomedical research innovations and converts them into prevention methods, diagnostic tools and therapies. Moreover, epidemiological research is not integrated with other types of cancer research, and the implementation of the European Directives on Clinical Trials 1 and on Personal Data Protection 2 has further slowed the innovation process in Europe. Furthermore, large inequalities in health and research exist between the EU–15 and the New Member States.
The picture is not entirely bleak, however, as the European cancer research scene presents several strengths, such as excellent basic research and clinical research and innovative etiological research that should be better exploited.
When considering recommendations, several priority dimensions had to be retained. It is essential that proposals include actions and recommendations that can benefit all Member States of the European Union and not just States with the elite centres. It is also essential to have a broader patient orientation to help provide the knowledge to establish cancer control possibilities when we exhaust what can be achieved by the implementation of current knowledge. It is vital that the actions proposed can contribute to the Lisbon Strategy to make Europe more innovative and competitive in (cancer) research.
The Project participants identified six areas for which consensus solutions should be implemented in order to obtain better coordination of cancer research activities. The required solutions are as follows. The proactive management of innovation, detection, facilitation of collaborations and maintenance of healthy competition within the European cancer research community.The establishment of an exchange portal of information for health professionals, patients and policy makers.The provision of guidance for translational and clinical research including the establishment of a translational research platform involving comprehensive cancer centres and cancer research centres.The coordination of calls and financial management of cancer research projects.The construction of a ‘one–stop shop’ as a contact interface between the industry, small and medium enterprises, scientists and other stakeholders.The support of greater involvement of healthcare professionals in translational research and multidisciplinary training.
In the course of the EUROCAN+PLUS consultative process, several key collaborative projects emerged between the various groups and institutes engaged in the consultation. There was a collaboration network established with Europe’s leading Comprehensive Cancer Centres; funding was awarded for a closer collaboration of Owners of Cancer Registries in Europe (EUROCOURSE); there was funding received from FP7 for an extensive network of leading Biological Resource Centres in Europe (BBMRI); a Working Group identified the special needs of Central, Eastern and South–eastern Europe and proposed a remedy (‘Warsaw Declaration’), and the concept of developing a one–stop shop for dealing with academia and industry including the Innovative Medicines Initiative (IMI) was discussed in detail.
Several other dimensions currently lacking were identified. There is an absolute necessity to include the patients’ voice in the establishment of priority areas in cancer research at the present time. It was a salutary lesson when it was recognized that all that is known about the quality of life of the cancer patient comes from the experience of a tiny proportion of cancer patients included in a few clinical trials. The necessity to have dialogue between funders and scientists to establish the best mechanisms to meet the needs of the entire community was evident. A top priority should be the development of translational research (in its widest form) and the development of effective and innovative cancer treatments and preventative strategies in the European Union. Translational research ranges from bench-to-bedside innovative cancer therapies and extends to include bringing about changes in population behaviours when a risk factor is established.
Having taken note of the barriers and the solutions and having examined relevant examples of existing European organizations in the field, it was agreed during the General Assembly of 19 November 2007 that the EUROCAN+PLUS Project had to recommend the creation of a small, permanent and neutral ECI. This should be a model structure and was widely supported at both General Assemblies of the project. The proposal is based on the successful model of the European Molecular Biology Organisation (EMBO), and its principal aims include providing a forum where researchers from all backgrounds and from all countries can meet with members of other specialities including patients, nurses, clinicians, funders and scientific administrators to develop priority programmes to make Europe more competitive in research and more focused on the cancer patient.
The ECI should assume responsibility for: stimulating innovative cancer research and facilitating processes;becoming the common voice of the cancer research community and serving as an interface between the cancer research community and European citizens, patients’ and organizations;European institutions, Member States, industry and small and medium enterprises;putting into practice the aforementioned solutions aimed at alleviating barriers and coordinating cancer research activities in the EU;dealing with legal and regulatory issues.
Solutions implemented through the ECI will lead to better coordination and collaboration throughout Europe, more efficient use of resources, an increase in Europe’s attractiveness to the biomedical industry and better quality of cancer research and education of health professionals.
The Project considered that European legal instruments currently available were inadequate for addressing many aspects of the barriers identified and for the implementation of effective, lasting solutions. Therefore, the legal environment that could shelter an idea like the ECI remains to be defined but should be done so as a priority. In this context, the initiative of the European Commission for a new legal entity for research infrastructure might be a step in this direction. The development of an effective ECI will require time, but this should be established immediately. As an initial step, coordination efforts should be directed towards the creation of a platform on translational research that could encompass: (1) coordination between basic, clinical and epidemiological research; (2) formal agreements of co-operation between comprehensive cancer centres and basic research laboratories throughout Europe; (3) networking between funding bodies at the European level. Another topic deserving immediate attention is the creation of a European database on cancer research projects and cancer research facilities.
Despite enormous progress in cancer control in Europe during the past two decades, there was an increase of 300,000 in the number of new cases of cancer diagnosed between 2004 and 2006. The European Parliament and its instruments have had a major influence in cancer control, notably in tobacco control and in the implementation of effective population–based screening. To make further progress there is a need for novelty and innovation in cancer research and prevention in Europe, and having a platform such as the ECI, where those involved in all aspects of cancer research can meet, discuss and interact, is a decisive development for Europe.
doi:10.3332/ecancer.2011.84
PMCID: PMC3234055  PMID: 22274749
20.  Cholinesterase Inhibitors in Mild Cognitive Impairment: A Systematic Review of Randomised Trials 
PLoS Medicine  2007;4(11):e338.
Background
Mild cognitive impairment (MCI) refers to a transitional zone between normal ageing and dementia. Despite the uncertainty regarding the definition of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs) currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD), in preventing progression from MCI to AD. The objective of this review is to assess the effects of ChEIs (donepezil, rivastigmine, and galantamine) in delaying the conversion from MCI to Alzheimer disease or dementia.
Methods and Findings
The terms “donepezil”, “rivastigmine”, “galantamine”, and “mild cognitive impairment” and their variants, synonyms, and acronyms were used as search terms in four electronic databases (MEDLINE, EMBASE, Cochrane, PsycINFO) and three registers: the Cochrane Collaboration Trial Register, Current Controlled Trials, and ClinicalTrials.gov. Published and unpublished studies were included if they were randomized clinical trials published (or described) in English and conducted among persons who had received a diagnosis of MCI and/or abnormal memory function documented by a neuropsychological assessment. A standardized data extraction form was used. The reporting quality was assessed using the Jadad scale. Three published and five unpublished trials met the inclusion criteria (three on donepezil, two on rivastigmine, and three on galantamine). Enrolment criteria differed among the trials, so the study populations were not homogeneous. The duration of the trials ranged from 24 wk to 3 y. No significant differences emerged in the probability of conversion from MCI to AD or dementia between the treated groups and the placebo groups. The rate of conversion ranged from 13% (over 2 y) to 25% (over 3 y) among treated patients, and from 18% (over 2 y) to 28% (over 3 y) among those in the placebo groups. Only for two studies was it possible to derive point estimates of the relative risk of conversion: 0.85 (95% confidence interval 0.64–1.12), and 0.84 (0.57–1.25). Statistically significant differences emerged for three secondary end points. However, when adjusting for multiple comparisons, only one difference remained significant (i.e., the rate of atrophy in the whole brain).
Conclusions
The use of ChEIs in MCI was not associated with any delay in the onset of AD or dementia. Moreover, the safety profile showed that the risks associated with ChEIs are not negligible. The uncertainty regarding MCI as a clinical entity raises the question as to the scientific validity of these trials.
A systematic review of trials of cholinesterase inhibitors for preventing transition of mild cognitive impairment (MCI) to dementia, conducted by Roberto Raschetti and colleagues, found no difference between treatment and control groups and concluded that uncertainty regarding the definition of MCI casts doubts on the validity of such trials.
Editors' Summary
Background.
Worldwide, more than 24 million people have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. The commonest form of dementia is Alzheimer disease (AD). The risk of developing AD increases with age—AD is rare in people younger than 65 but about half of people over 85 years old have it. The earliest symptom of AD is usually difficulty in remembering new information. As the disease progresses, patients may become confused and have problems expressing themselves. Their behavior and personality can also change. In advanced AD, patients need help with daily activities like dressing and eating, and eventually lose their ability to recognize relatives and to communicate. There is no cure for AD but a class of drugs called “cholinesterase inhibitors” can sometimes temporarily slow the worsening of symptoms. Three cholinesterase inhibitors—donepezil, rivastigmine, and galantamine—are currently approved for use in mild-to-moderate AD.
Why Was This Study Done?
Some experts have questioned the efficacy of cholinesterase inhibitors in AD, but other experts and patient support groups have called for these drugs to be given to patients with a condition called mild cognitive impairment (MCI) as well as to those with mild AD. People with MCI have memory problems that are more severe than those normally seen in people of their age but no other symptoms of dementia. They are thought to have an increased risk of developing AD, but it is not known whether everyone with MCI eventually develops AD, and there is no standardized way to diagnose MCI. Despite these uncertainties, several clinical trials have investigated whether cholinesterase inhibitors prevent progression from MCI to AD. In this study, the researchers have assessed whether the results of these trials provide any evidence that cholinesterase inhibitors can prevent MCI progressing to AD.
What Did the Researchers Do and Find?
The researchers conducted a systematic review of the medical literature to find trials that had addressed this issue, which met criteria that they had defined clearly in advance of their search. They identified three published and five unpublished randomized controlled trials (studies in which patients randomly receive the test drug or an inactive placebo) that investigated the effect of cholinesterase inhibitors on the progression of MCI. The researchers obtained the results of six of these trials—four examined the effect of cholinesterase inhibitors on the conversion of MCI to clinically diagnosed AD or dementia (the primary end point); all six examined the effect of the drugs on several secondary end points (for example, individual aspects of cognitive function). None of the drugs produced a statistically significant difference (a difference that is unlikely to have happened by chance) in the probability of progression from MCI to AD. The only statistically significant secondary end point after adjustment for multiple comparisons (when many outcomes are considered, false positive results can occur unless specific mathematical techniques are used to prevent this problem) was a decrease in the rate of brain shrinkage associated with galantamine treatment. More patients treated with cholinesterase inhibitors dropped out of trials because of adverse effects than patients given placebo. Finally, in the one trial that reported all causes of deaths, one participant who received placebo and six who received galantamine died.
What Do These Findings Mean?
These findings suggest that the use of cholinesterase inhibitors is not associated with any delay in the onset of clinically diagnosed AD or dementia in people with MCI. They also show that the use of these drugs has no effect on most surrogate (substitute) indicators of AD but that the risks associated with their use are not negligible. However, because MCI has not yet been clearly defined as a clinical condition that precedes dementia, some (even many) of the patients enrolled into the trials that the researchers assessed may not actually have had MCI. Thus, further clinical trials are needed to clarify whether cholinesterase inhibitors can delay the progression of MCI to dementia, but these additional trials should not be done until the diagnosis of MCI has been standardized.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040338.
An essay by Matthews and colleagues, in the October 2007 issue of PLoS Medicine, discusses how mild cognitive impairment is currently diagnosed
The US Alzheimer's Association provides information about all aspects of Alzheimer disease, including fact sheets on treatments for Alzheimer disease and on mild cognitive impairment
The UK Alzheimer's Society provides information for patients and caregivers on all aspects of dementia, including drug treatments and mild cognitive impairment
The UK charity DIPEx provides short video clips of personal experiences of care givers of people with dementia
doi:10.1371/journal.pmed.0040338
PMCID: PMC2082649  PMID: 18044984
21.  A Boost for the Emerging Field of RNA Nanotechnology 
ACS Nano  2011;5(5):3405-3418.
This Nano Focus article highlights recent advances in RNA nanotechnology as presented at the First International Conference of RNA Nanotechnology and Therapeutics, which took place in Cleveland, OH, USA (October 23–25, 2010) (http://www.eng.uc.edu/nanomedicine/RNA2010/), chaired by Peixuan Guo and co-chaired by David Rueda and Scott Tenenbaum. The conference was the first of its kind to bring together more than 30 invited speakers in the frontier of RNA nanotechnology from France, Sweden, South Korea, China, and throughout the United States to discuss RNA nanotechnology and its applications. It provided a platform for researchers from academia, government, and the pharmaceutical industry to share existing knowledge, vision, technology, and challenges in the field and promoted collaborations among researchers interested in advancing this emerging scientific discipline. The meeting covered a range of topics, including biophysical and single-molecule approaches for characterization of RNA nanostructures; structure studies on RNA nanoparticles by chemical or biochemical approaches, computation, prediction, and modeling of RNA nanoparticle structures; methods for the assembly of RNA nanoparticles; chemistry for RNA synthesis, conjugation, and labeling; and application of RNA nanoparticles in therapeutics. A special invited talk on the well-established principles of DNA nanotechnology was arranged to provide models for RNA nanotechnology. An Administrator from National Institutes of Health (NIH) National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer discussed the current nanocancer research directions and future funding opportunities at NCI. As indicated by the feedback received from the invited speakers and the meeting participants, this meeting was extremely successful, exciting, and informative, covering many groundbreaking findings, pioneering ideas, and novel discoveries.
doi:10.1021/nn200989r
PMCID: PMC3102291  PMID: 21604810
22.  Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis 
PLoS Medicine  2013;10(5):e1001454.
Jürgen Barth and colleagues use network meta-analysis - a novel methodological approach - to reexamine the comparative efficacy of seven psychotherapeutic interventions for adults with depression.
Please see later in the article for the Editors' Summary
Background
Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.
Methods and Findings
We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = −0.62 to d = −0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = −0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = −0.30, 95% credibility interval [CrI] [−0.54 to −0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [−0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [−0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions.
Conclusions
Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Depression is a very common condition. One in six people will experience depression at some time during their life. People who are depressed have recurrent feelings of sadness and hopelessness and might feel that life is no longer worth living. The condition can last for months and often includes physical symptoms such as headaches, sleeping problems, and weight gain or loss. Treatment of depression can include non-drug treatments (psychotherapy), antidepressant drugs, or a combination of the two. Especially for people with mild or intermediate depression, psychotherapy is often considered the preferred first option. Psychotherapy describes a range of different psychotherapies, and a number of established types of psychotherapies have all shown to work for at least some patients.
Why Was This Study Done?
While it is broadly accepted that psychotherapy can help people with depression, the question of which type of psychotherapy works best for most patients remains controversial. While many scientific studies have compared one psychotherapy with control conditions, there have been few studies that directly compared multiple treatments. Without such direct comparisons, it has been difficult to establish the respective merits of the different types of psychotherapy. Taking advantage of a recently developed method called “network meta-analysis,” the authors re-examine the evidence on seven different types of psychotherapy to see how well they have been shown to work and whether some work better than others.
What Did the Researchers Do and Find?
The researchers looked at seven different types of psychotherapy, which they defined as follows. “Interpersonal psychotherapy” is short and highly structured, using a manual to focus on interpersonal issues in depression. “Behavioral activation” raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment. “Cognitive behavioral therapy” focuses on a patient's current negative beliefs, evaluates how they affect current and future behavior, and attempts to restructure the beliefs and change the outlook. “Problem solving therapy” aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution. “Psychodynamic therapy” focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation. In “social skills therapy,” patients are taught skills that help to build and maintain healthy relationships based on honesty and respect. “Supportive counseling” is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.
The researchers started with a systematic search of the medical literature for relevant studies. The search identified 198 articles that reported on such clinical trials. The trials included a total of 15,118 patients and compared one of the seven psychotherapies either with another one or with a common “control intervention”. In most cases, the control (no psychotherapy) was deferral of treatment by “wait-listing” patients or continuing “usual care.” With network meta-analysis they were able to summarize the results of all these trials in a meaningful way. They did this by integrating direct comparisons of several psychotherapies within the same trial (where those were available) with indirect comparisons across all trials (using no psychotherapy as a control intervention).
Based on the combined trial results, all seven psychotherapies tested were better than wait-listing or usual care, and the differences were moderate to large, meaning that the average person in the group that received therapy was better off than about half of the patients in the control group. When comparing the therapies with each other, the researchers saw small or no differences, meaning that none of them really stood out as much better or much worse than the others. They also found that the treatments worked equally well for different patient groups with depression (younger or older patients, or mothers who had depression after having given birth). Similarly, they saw no big differences when comparing individual with group therapy, or person-to-person with internet-based interactions between therapist and patient.
However, they did find that smaller and less rigorous studies generally found larger benefits of psychotherapies, and most of the studies included in the analysis were small. Only 36 of the studies had at least 50 patients who received the same treatment. When they restricted their analysis to those studies, the researchers still saw clear benefits of cognitive-behavioral therapy, interpersonal therapy, and problem-solving therapy, but not for the other four therapies.
What Do these Findings Mean?
Similar to earlier attempts to summarize and make sense of the many study results, this one finds benefits for all of the seven psychotherapies examined, and none of them stood as being much better than some or all others. The scientific support for being beneficial was stronger for some therapies, mostly because they had been tested more often and in larger studies.
Treatments with proven benefits still do not necessarily work for all patients, and which type of psychotherapy might work best for a particular patient likely depends on that individual. So overall this analysis suggests that patients with depression and their doctors should consider psychotherapies and explore which of the different types might be best suited for a particular patient.
The study also points to the need for further research. Whereas depression affects large numbers of people around the world, all of the trials identified were conducted in rich countries and Western societies. Trials in different settings are essential to inform treatment of patients worldwide. In addition, large high-quality studies should further explore the potential benefits of some of therapies for which less support currently exists. Where possible, future studies should compare psychotherapies with one another, because all of them have benefits, and it would not be ethical to withhold such beneficial treatment from patients.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001454.
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish); information on psychotherapy includes information on its most common forms
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
The UK nonprofit Mind provides information on depression, including an explanation of the most common psychotherapies in the UK
MedlinePlus provides links to other resources about depression (in English and Spanish)
The UK nonprofit healthtalkonline.org has a unique database of personal and patient experiences on depression
doi:10.1371/journal.pmed.1001454
PMCID: PMC3665892  PMID: 23723742
23.  The international effort: building the bridge for Translational Medicine: Report of the 1st International Conference of Translational Medicine (ICTM) 
Background
Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad.
Findings
The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two-way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation.
Conclusions
It was the meeting participants’ realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two-fold: to accelerate the two-way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state-of-art translational research and salient aspects of the ensuing discussions.
doi:10.1186/2001-1326-1-15
PMCID: PMC3561055  PMID: 23369397
Translational Medicine (TM); International Society for Translational Medicine (ISTM); the International Conference on Translational Medicine (ICTM); Biomarkers; Biobank globalization and networking
24.  The Connection Between Academia and Industry 
Mens Sana Monographs  2005;3(1):5-35.
The growing commercialization of research with its effect on the ethical conduct of researchers, and the advancement of scientific knowledge with its effect on the welfare or otherwise of patients, are areas of pressing concern today and need a serious, thorough study. Biomedical research, and its forward march, is becoming increasingly dependent on industry-academia proximity, both commercial and geographic. A realization of the commercial value of academic biomedical research coupled with its rapid and efficient utilization by industry is the major propelling force here. A number of well-intentioned writers in the field look to the whole development with optimism. But this partnership is a double-edged sword, for it carries with it the potential of an exciting future as much as the prospect of misappropriation and malevolence. Moreover, such partnerships have sometimes eroded public trust in the research enterprise itself.
Connected to the growing clout of industry in institutions is concern about thecommercialization of research and resolving the ‘patient or product’ loyalty.
There is ambivalence about industry funding and influence in academia, and a consequent ‘approach-avoidance’ conflict. If academia has to provide the patients and research talent, industry necessarily has to provide the finances and other facilities based on it. This is an invariable and essential agreement between the two parties that they can walk out of only at their own peril. The profound ethical concerns that industry funded research has brought center-stage need a close look, especially as they impact patients, research subjects, public trust, marketability of products, and research and professional credibility.
How can the intermediate goal of industry (patient welfare) serve the purpose of the final goal of academia is the basic struggle for conscientious research institutions /associations. And how best the goal of maximizing profits can be best served, albeit suitably camouflaged as patient welfare throughout, is the concern of the pharmaceutical industry.
A very great potential conflict of interest lies in the fact that academia needs the sophisticated instruments that only big funding can provide, while at the same time resists the attempts of the fund provider to set the agenda of research, protocol, design, publication, the works. Conflicts arise at many steps and levels of functioning, and are related to the expectations, competing interests, and conflicting priorities of the different entities involved, whether they are the academic medical centers, the funding agencies, the patients and their families, or the investors and venture capitalists.
The public expects access to new treatments. Its appetite for innovation has been bolstered by the constant attention given by the press to new treatments and by the implicit promise from researchers of continuing advances. Similarly, patients demand privacy and control over information about themselves.
It makes greater sense for genuine researchers to associate with large long-term industry players who have a track record of genuine hard-core discoveries, even if the process is slow (maybe), and the funding less (may not be).
The element of control venture capitalists exert over the pharmaceutical industry is an under researched area for obvious reasons. But it needs further probing, for that will lay bare the pulls and pressures under which industry works.
It makes sense for ethically minded researchers and institutions not to fall in the trap of stocks and equity investments in industry, howsoever attractive they appear, and get rid of them as soon as possible if they have them. If at all they want, it makes more sense to own stocks of larger well established concerns, for the stock upheavals being less, the pressure of the market-place, and of venture sharks, is likely to be lower too.
While active participation by the researcher in the commercialization process may be greatly desired by industry, ostensibly in the name of creating value, academia must realize it is a bait it might find hard to swallow in the long run. It makes more sense for the researcher and institution to forego such temptations and/or walk out of such investments as soon as possible.
While mainstream medicine and research are booming, as is connected industry, concerns about professional commitment to patient welfare are growing too. Increasing corporate influence is challenging certain long held and fundamental values of patient care, which will have far reaching implications for biomedical care and the future progress of mainstream medicine.
doi:10.4103/0973-1229.27876
PMCID: PMC3369181  PMID: 22679346
Academia; Pharmaceutical Industry; Academia-Industry Proximity; Biomedical Research; Commercialization of Research; Pharmaceutical Funding; Public Accountability and Academic Freedom of Universities
25.  Alzheimer’s Disease and Age-Related Memory Decline (Preclinical) 
An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function.
doi:10.1016/j.pbb.2011.02.002
PMCID: PMC3113643  PMID: 21315756
cognition; drug development; pro-cognitive; neurotransmitter receptors; Mild Cognitive Impairment; dementia

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