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1.  Tobacco industry strategies to undermine the 8th World Conference on Tobacco or Health 
Tobacco Control  2003;12(2):195-202.
Objective: To demonstrate that Philip Morris and British American Tobacco Company attempted to initiate a wide ranging campaign to undermine the success of the 8th World Conference on Tobacco or Health held in Buenos Aires, Argentina, in 1992.
Data sources: Publicly available tobacco industry documents housed in Minneapolis, Minnesota, USA; Guilford, UK; on-line document websites; and telephone interviews with informed parties.
Study selection: Those documents determined to be relevant to the companies' campaigns against the 8th World Conference on Tobacco or Health.
Data extraction: Revision of chapter VIII of the July 2000 WHO report by a committee of experts, entitled: Tobacco company strategies to undermine tobacco control activities at the World Health Organization: report of the committee of experts on tobacco industry documents.
Data synthesis: Internal documents describe proposed media and science orientated campaigns developed by BAT, Philip Morris, and their consultants to divert attention away from the conference.
Results and conclusion: This work shows that the tobacco industry has the resources and vested interest to combat perceived threats in its regional operating markets, in this case its Latin American market. It is important for the worldwide public heath community to become aware of the numerous ways in which the tobacco industry and its front groups can work against international tobacco control meetings, even including the manipulation of or working with other public health groups to oppose tobacco control efforts. Future world conference planners and participants should be aware that the tobacco industry is likely to continue to employ such methodology. There is no reason to think that the industry is paying less attention to such conferences in the present or future. Rather, it is likely the industry will adopt and expand strategies that were successful while abandoning those that were not effective. Required disclosure of financial support by all participants at all tobacco scientific conferences is recommended. For the tobacco control community, we also recommend careful coalition building and networking with other public health groups on the ways tobacco is implicated in other public health issues.
PMCID: PMC1747698  PMID: 12773731
2.  Interactions between Non-Physician Clinicians and Industry: A Systematic Review 
PLoS Medicine  2013;10(11):e1001561.
In a systematic review of studies of interactions between non-physician clinicians and industry, Quinn Grundy and colleagues found that many of the issues identified for physicians' industry interactions exist for non-physician clinicians.
Please see later in the article for the Editors' Summary
With increasing restrictions placed on physician–industry interactions, industry marketing may target other health professionals. Recent health policy developments confer even greater importance on the decision making of non-physician clinicians. The purpose of this systematic review is to examine the types and implications of non-physician clinician–industry interactions in clinical practice.
Methods and Findings
We searched MEDLINE and Web of Science from January 1, 1946, through June 24, 2013, according to PRISMA guidelines. Non-physician clinicians eligible for inclusion were: Registered Nurses, nurse prescribers, Physician Assistants, pharmacists, dieticians, and physical or occupational therapists; trainee samples were excluded. Fifteen studies met inclusion criteria. Data were synthesized qualitatively into eight outcome domains: nature and frequency of industry interactions; attitudes toward industry; perceived ethical acceptability of interactions; perceived marketing influence; perceived reliability of industry information; preparation for industry interactions; reactions to industry relations policy; and management of industry interactions. Non-physician clinicians reported interacting with the pharmaceutical and infant formula industries. Clinicians across disciplines met with pharmaceutical representatives regularly and relied on them for practice information. Clinicians frequently received industry “information,” attended sponsored “education,” and acted as distributors for similar materials targeted at patients. Clinicians generally regarded this as an ethical use of industry resources, and felt they could detect “promotion” while benefiting from industry “information.” Free samples were among the most approved and common ways that clinicians interacted with industry. Included studies were observational and of varying methodological rigor; thus, these findings may not be generalizable. This review is, however, the first to our knowledge to provide a descriptive analysis of this literature.
Non-physician clinicians' generally positive attitudes toward industry interactions, despite their recognition of issues related to bias, suggest that industry interactions are normalized in clinical practice across non-physician disciplines. Industry relations policy should address all disciplines and be implemented consistently in order to mitigate conflicts of interest and address such interactions' potential to affect patient care.
Please see later in the article for the Editors' Summary
Editors' Summary
Making and selling health care goods (including drugs and devices) and services is big business. To maximize the profits they make for their shareholders, companies involved in health care build relationships with physicians by providing information on new drugs, organizing educational meetings, providing samples of their products, giving gifts, and holding sponsored events. These relationships help to keep physicians informed about new developments in health care but also create the potential for causing harm to patients and health care systems. These relationships may, for example, result in increased prescription rates of new, heavily marketed medications, which are often more expensive than their generic counterparts (similar unbranded drugs) and that are more likely to be recalled for safety reasons than long-established drugs. They may also affect the provision of health care services. Industry is providing an increasingly large proportion of routine health care services in many countries, so relationships built up with physicians have the potential to influence the commissioning of the services that are central to the treatment and well-being of patients.
Why Was This Study Done?
As a result of concerns about the tension between industry's need to make profits and the ethics underlying professional practice, restrictions are increasingly being placed on physician–industry interactions. In the US, for example, the Physician Payments Sunshine Act now requires US manufacturers of drugs, devices, and medical supplies that participate in federal health care programs to disclose all payments and gifts made to physicians and teaching hospitals. However, other health professionals, including those with authority to prescribe drugs such as pharmacists, Physician Assistants, and nurse practitioners are not covered by this legislation or by similar legislation in other settings, even though the restructuring of health care to prioritize primary care and multidisciplinary care models means that “non-physician clinicians” are becoming more numerous and more involved in decision-making and medication management. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the researchers examine the nature and implications of the interactions between non-physician clinicians and industry.
What Did the Researchers Do and Find?
The researchers identified 15 published studies that examined interactions between non-physician clinicians (Registered Nurses, nurse prescribers, midwives, pharmacists, Physician Assistants, and dieticians) and industry (corporations that produce health care goods and services). They extracted the data from 16 publications (representing 15 different studies) and synthesized them qualitatively (combined the data and reached word-based, rather than numerical, conclusions) into eight outcome domains, including the nature and frequency of interactions, non-physician clinicians' attitudes toward industry, and the perceived ethical acceptability of interactions. In the research the authors identified, non-physician clinicians reported frequent interactions with the pharmaceutical and infant formula industries. Most non-physician clinicians met industry representatives regularly, received gifts and samples, and attended educational events or received educational materials (some of which they distributed to patients). In these studies, non-physician clinicians generally regarded these interactions positively and felt they were an ethical and appropriate use of industry resources. Only a minority of non-physician clinicians felt that marketing influenced their own practice, although a larger percentage felt that their colleagues would be influenced. A sizeable proportion of non-physician clinicians questioned the reliability of industry information, but most were confident that they could detect biased information and therefore rated this information as reliable, valuable, or useful.
What Do These Findings Mean?
These and other findings suggest that non-physician clinicians generally have positive attitudes toward industry interactions but recognize issues related to bias and conflict of interest. Because these findings are based on a small number of studies, most of which were undertaken in the US, they may not be generalizable to other countries. Moreover, they provide no quantitative assessment of the interaction between non-physician clinicians and industry and no information about whether industry interactions affect patient care outcomes. Nevertheless, these findings suggest that industry interactions are normalized (seen as standard) in clinical practice across non-physician disciplines. This normalization creates the potential for serious risks to patients and health care systems. The researchers suggest that it may be unrealistic to expect that non-physician clinicians can be taught individually how to interact with industry ethically or how to detect and avert bias, particularly given the ubiquitous nature of marketing and promotional materials. Instead, they suggest, the environment in which non-physician clinicians practice should be structured to mitigate the potentially harmful effects of interactions with industry.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by James S. Yeh and Aaron S. Kesselheim
The American Medical Association provides guidance for physicians on interactions with pharmaceutical industry representatives, information about the Physician Payments Sunshine Act, and a toolkit for preparing Physician Payments Sunshine Act reports
The International Council of Nurses provides some guidance on industry interactions in its position statement on nurse-industry relations
The UK General Medical Council provides guidance on financial and commercial arrangements and conflicts of interest as part of its good medical practice website, which describes what is required of all registered doctors in the UK
Understanding and Responding to Pharmaceutical Promotion: A Practical Guide is a manual prepared by Health Action International and the World Health Organization that schools of medicine and pharmacy can use to train students how to recognize and respond to pharmaceutical promotion.
The Institute of Medicine's Report on Conflict of Interest in Medical Research, Education, and Practice recommends steps to identify, limit, and manage conflicts of interest
The University of California, San Francisco, Office of Continuing Medical Education offers a course called Marketing of Medicines
PMCID: PMC3841103  PMID: 24302892
3.  Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. 
Journal of Clinical Investigation  1988;82(4):1236-1243.
Activated protein C (APC) acts as a potent anticoagulant enzyme by inactivating Factor V and Factor VIII. In this study, protein S was shown to increase the inactivation of purified Factor VIII by APC ninefold. The reaction rate was saturated with respect to the concentration of protein S when protein S was present in a 10-fold molar excess over APC. The heavy chain of Factor VIII was cleaved by APC and protein S did not alter the degradation pattern. Factor VIII circulates in a complex with the adhesive protein von Willebrand factor. When purified Factor VIII was recombined with von Willebrand factor, the inactivation of Factor VIII by APC proceeded at a 10-20-fold slower rate as compared with Factor VIII in the absence of von Willebrand factor. Protein S had no effect on the inactivation of the Factor VIII-von Willebrand factor complex by APC. After treatment of this complex with thrombin, however, the actions of APC and protein S towards Factor VIII were completely restored. In hemophilia A plasma, purified Factor VIII associated with endogenous von Willebrand factor, resulting in a complete protection against APC (4 nM). By mixing hemophilic plasma with plasma from a patient with severe von Willebrand's disease, we could vary the amount of von Willebrand factor. 1 U of von Willebrand factor was needed to provide protection of 1 U Factor VIII. Also in plasma from patients with the IIA-type variant of von Willebrand's disease, Factor VIII was protected. In von Willebrand's disease plasma, which was depleted of protein S, APC did not inactivate Factor VIII. These results indicate that protein S serves as a cofactor in the inactivation of Factor VIII and Factor VIIIa by APC and that von Willebrand factor can regulate the action of these two anticoagulant proteins.
PMCID: PMC442674  PMID: 2971673
4.  Environmental threats to children's health in Southeast Asia and the Western Pacific. 
Environmental Health Perspectives  2003;111(10):1340-1347.
The Southeast Asia and Western Pacific regions contain half of the world's children and are among the most rapidly industrializing regions of the globe. Environmental threats to children's health are widespread and are multiplying as nations in the area undergo industrial development and pass through the epidemiologic transition. These environmental hazards range from traditional threats such as bacterial contamination of drinking water and wood smoke in poorly ventilated dwellings to more recently introduced chemical threats such as asbestos construction materials; arsenic in groundwater; methyl isocyanate in Bhopal, India; untreated manufacturing wastes released to landfills; chlorinated hydrocarbon and organophosphorous pesticides; and atmospheric lead emissions from the combustion of leaded gasoline. To address these problems, pediatricians, environmental health scientists, and public health workers throughout Southeast Asia and the Western Pacific have begun to build local and national research and prevention programs in children's environmental health. Successes have been achieved as a result of these efforts: A cost-effective system for producing safe drinking water at the village level has been devised in India; many nations have launched aggressive antismoking campaigns; and Thailand, the Philippines, India, and Pakistan have all begun to reduce their use of lead in gasoline, with resultant declines in children's blood lead levels. The International Conference on Environmental Threats to the Health of Children, held in Bangkok, Thailand, in March 2002, brought together more than 300 representatives from 35 countries and organizations to increase awareness on environmental health hazards affecting children in these regions and throughout the world. The conference, a direct result of the Environmental Threats to the Health of Children meeting held in Manila in April 2000, provided participants with the latest scientific data on children's vulnerability to environmental hazards and models for future policy and public health discussions on ways to improve children's health. The Bangkok Statement, a pledge resulting from the conference proceedings, is an important first step in creating a global alliance committed to developing active and innovative national and international networks to promote and protect children's environmental health.
PMCID: PMC1241616  PMID: 12896856
5.  Facilitating and inhibiting factors for long-term involvement of patients at outcome conferences—lessons learnt from a decade of collaboration in OMERACT: a qualitative study 
BMJ Open  2013;3(8):e003311.
Several studies have provided insights into the conditions for successful patient involvement in health research. We recently demonstrated that long-term engagement with people with rheumatic conditions in international outcome research led to significant changes in the research agenda in the field of rheumatology. This article explores facilitating and inhibiting factors for long-term involvement of patients as collaborative partners at five Outcome Measures in Rheumatology (OMERACT) conferences.
Responsive evaluation, starting with a thematic document analysis of conference proceedings and the grey literature, followed by 38 qualitative interviews. Interview transcripts were subjected to inductive content analysis.
5 international OMERACT conferences between 2002 and 2012.
Patient delegates (n=16) and professional delegates representing researchers (n=14), pharmaceutical industry and regulators (n=2).
Combined review of the document analysis and interview data revealed five main facilitators and three main barriers. Patient engagement as full participants at OMERACT conferences was enhanced by: strong leadership commitment and the presence of change agents, a clear selection procedure, an inclusive consensus-based conference design, individualised and self-organised support, an interactive and encouraging moderation style during discussion groups. Barriers were related to the intensity of the conference programme, scepticism among researchers and doubts about the representativeness of the patient group.
This study concludes that developing a sustainable structure for funding, selection and support of patient delegates, as well as adjusting conference design and moderation style, contributes not only towards facilitating direct dialogue between all stakeholders but also towards enhancing mutual understanding and the successful incorporation of the patient perspective in an outcome conference such as OMERACT.
PMCID: PMC3753501  PMID: 23975104
Qualitative Research; Rheumatology; Social Medicine
6.  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
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.
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
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
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, from the US National Cancer Institute, offers online tools and resources to help people quit smoking
PMCID: PMC3665841  PMID: 23723740
7.  Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis 
Objective To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee.
Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points.
Main outcome measure Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at −0.9 cm on a 10 cm visual analogue scale.
Data sources Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites.
Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head.
Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was −0.4 cm (95% credible interval −0.7 to −0.1 cm) for glucosamine, −0.3 cm (−0.7 to 0.0 cm) for chondroitin, and −0.5 cm (−0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero.
Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.
PMCID: PMC2941572  PMID: 20847017
8.  ISMB/ECCB 2009 Stockholm 
Bioinformatics  2009;25(12):1570-1573.
The International Society for Computational Biology (ISCB; 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;, 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 ( follows the framework introduced at the ISMB/ECCB 2007 ( in Vienna, and further refined at the ISMB 2008 ( 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.
PMCID: PMC2687994  PMID: 19447790
9.  Role of the liver-enriched transcription factor hepatocyte nuclear factor 1 in transcriptional regulation of the factor V111 gene. 
Molecular and Cellular Biology  1996;16(5):1936-1945.
Coagulation factor VIII is an essential cofactor required for normal hemostatic function. A deficiency in factor VIII results in the bleeding disorder hemophilia A. Despite the fact that the factor VIII gene was cloned a decade ago, the mechanisms which control its transcription remain unresolved. In our studies, we have characterized 12 protein binding sites within the factor VIII promoter by DNase I protection assays performed with rat liver nuclear extracts. Three of these elements (sites 1 to 3) are situated within the 5' untranslated region of the gene, while three other sites (sites 4 to 6) lie within the first 100 bp upstream of the transcriptional start site. We have identified an additional site (site 7) approximately 300 bp upstream from site 6, as well as a cluster of five sites in a 250-bp region which terminates approximately 1 kb from the transcriptional start site. Seven of these binding sites (sites 2, 3, 4, 6, 7, 9, and 10) bind members of the C/EBP family of transcription factors. DBP also binds to five of these sites (sites 3, 4, 6, 7, and 9). Utilizing transient transfection studies in HepG2 cells, we have shown that deletion of the factor VIII promoter sequences distal to nucleotide -44 results in a significant but small increase in promoter activity. The activity of each of the various 5' deletion constructs is significantly enhanced by cotransfection of C/EBPalpha and D-site-binding protein expression plasmids, while cotransfection of both C/EBPalpha and C/EBPbeta plasmids resulted in a further enhancement of transactivation. These studies also provide evidence of a repressor element located between nucleotides -740 and -1002. Since the minimal promoter sequence (-44 to +148) maintains the transcriptional activity of the full-length promoter sequence, we proceeded to identify additional factors binding to sites 1 to 4. Competition studies revealed that a ubiquitous transcription factor, NF-Y, binds to site 4, while the liver-enriched transcription factor hepatocyte nuclear factor I (HNF-1) binds to site 1. Mutation analysis of the minimal promoter demonstrated that HNF-1 is critical for activating transcription of the factor VIII gene in vitro. Our results also suggest that the multiple upstream elements that we have identified may act as a backup regulatory region in the event of disruption of the HNF-1 element in the 5' untranslated region.
PMCID: PMC231181  PMID: 8628260
10.  Structural and Genetic Diversity of Group B Streptococcus Capsular Polysaccharides  
Infection and Immunity  2005;73(5):3096-3103.
Group B Streptococcus (GBS) is an important pathogen of neonates, pregnant women, and immunocompromised individuals. GBS isolates associated with human infection produce one of nine antigenically distinct capsular polysaccharides which are thought to play a key role in virulence. A comparison of GBS polysaccharide structures of all nine known GBS serotypes together with the predicted amino acid sequences of the proteins that direct their synthesis suggests that the evolution of serotype-specific capsular polysaccharides has proceeded through en bloc replacement of individual glycosyltransferase genes with DNA sequences that encode enzymes with new linkage specificities. We found striking heterogeneity in amino acid sequences of synthetic enzymes with very similar functions, an observation that supports horizontal gene transfer rather than stepwise mutagenesis as a mechanism for capsule variation. Eight of the nine serotypes appear to be closely related both structurally and genetically, whereas serotype VIII is more distantly related. This similarity in polysaccharide structure strongly suggests that the evolutionary pressure toward antigenic variation exerted by acquired immunity is counterbalanced by a survival advantage conferred by conserved structural motifs of the GBS polysaccharides.
PMCID: PMC1087335  PMID: 15845517
11.  Lack of Type VIII Collagen in Mice Ameliorates Diabetic Nephropathy 
Diabetes  2009;58(7):1672-1681.
Key features of diabetic nephropathy include the accumulation of extracellular matrix proteins. In recent studies, increased expression of type VIII collagen in the glomeruli and tubulointerstitium of diabetic kidneys has been noted. The objectives of this study were to assess whether type VIII collagen affects the development of diabetic nephropathy and to determine type VIII collagen–dependent pathways in diabetic nephropathy in the mouse model of streptozotocin (STZ)-induced diabetes.
Diabetes was induced by STZ injections in collagen VIII–deficient or wild-type mice. Functional and histological analyses were performed 40 days after induction of diabetes. Type VIII collagen expression was assessed by Northern blots, immunohistochemistry, and real-time PCR. Proliferation of primary mesangial cells was measured by thymidine incorporation and direct cell counting. Expression of phosphorylated extracellular signal–regulated kinase (ERK1/2) and p27Kip1 was assessed by Western blots. Finally, Col8a1 was stably overexpressed in mesangial cells.
Diabetic wild-type mice showed a strong renal induction of type VIII collagen. Diabetic Col8a1−/Col8a2− animals revealed reduced mesangial expansion and cellularity and extracellular matrix expansion compared with the wild type. These were associated with less albuminuria. High-glucose medium as well as various cytokines induced Col8a1 in cultured mesangial cells. Col8a1−/Col8a2− mesangial cells revealed decreased proliferation, less phosphorylation of Erk1/2, and increased p27Kip1 expression. Overexpression of Col8a1 in mesangial cells induced proliferation.
Lack of type VIII collagen confers renoprotection in diabetic nephropathy. One possible mechanism is that type VIII collagen permits and/or fosters mesangial cell proliferation in early diabetic nephropathy.
PMCID: PMC2699847  PMID: 19401424
12.  Selected science: an industry campaign to undermine an OSHA hexavalent chromium standard 
While exposure to hexavalent chromium (Cr(VI)) has been associated with increased lung cancer risk for more than 50 years, the chemical is not currently regulated by the U.S. Occupational Safety and Health Administration (OSHA) on the basis of its carcinogenicity. The agency was petitioned in 1993 and sued in 1997 and 2002 to lower the workplace Cr(VI) exposure limit, resulting in a court order to issue a final standard by February 2006. Faced with the threat of stronger regulation, the chromium industry initiated an effort to challenge the scientific evidence supporting a more protective standard. This effort included the use of "product defense" consultants to conduct post hoc analyses of a publicly-funded study to challenge results viewed unfavorably by the industry.
The industry also commissioned a study of the mortality experience of workers at four low-exposure chromium plants, but did not make the results available to OSHA in a timely manner, despite multiple agency requests for precisely these sorts of data. The commissioned study found a statistically significant elevation in lung cancer risk among Cr(VI)-exposed workers at levels far below the current standard. This finding changed when the multi-plant cohort was divided into two statistically underpowered components and then published separately. The findings of the first paper published have been used by the chromium industry to attempt to slow OSHA's standard setting process. The second paper was withheld from OSHA until it was accepted for publication in a scientific journal, after the rulemaking record had closed.
Studies funded by private sponsors that seek to influence public regulatory proceedings should be subject to the same access and reporting provisions as those applied to publicly funded science. Parties in regulatory proceedings should be required to disclose whether the studies were performed by researchers who had the right to present their findings without the sponsor's consent or influence, and to certify that all relevant data have been submitted to the public record, whether published or not.
PMCID: PMC1402271  PMID: 16504102
13.  Involving patient research partners has a significant impact on outcomes research: a responsive evaluation of the international OMERACT conferences 
BMJ Open  2013;3(5):e002241.
To assess the inclusion of patients as international research partners in Outcome Measures in Rheumatology (OMERACT) conferences and how this has influenced the scope and conduct of outcomes research in rheumatology.
A thematic content analysis of OMERACT internal documents, publications and conference proceedings, followed by a responsive evaluation including 32 qualitative semistructured interviews.
The international, biannual research conference OMERACT 10 (Malaysia, 2010).
Senior researchers (n=10), junior researchers (n=2), representatives of the pharmaceutical industry and regulators (n=2), conference staff (n=2), new patient delegates (n=8) and experienced patient delegates (n=8).
The role of patients evolved over 10 years from a single patient focus group to full participation in all areas of the meeting and inclusion in research group meetings between conferences. Five main categories of impact emerged: widening the research agenda; including patient relevant outcomes in core sets; enhancing patient reported instruments; changing the culture of OMERACT and consequences outside OMERACT. Patient participants identified previously neglected outcome domains such as fatigue, sleep disturbances and flares which prompted collaborative working on new programmes of research. Specific benefits and challenges for patients and professionals were identified, such as personal fulfilment, widening of research interests, difficulties in establishing equal partnerships and concerns about loss of research rigour.
Including patients as partners in OMERACT conferences has widened its focus and adjusted the way of working. It has resulted in new developments in the research agenda and the use of more patient-relevant outcomes in clinical trials. These collaborations have influenced perceptions and beliefs among many patients and researchers, and led to wider patient involvement as partners in research.
PMCID: PMC3651970  PMID: 23667160
Health impact assessment; Qualitative research; Rheumatology
14.  The Malaria in Pregnancy Library: a bibliometric review 
Malaria Journal  2012;11:362.
The Malaria in Pregnancy (MiP) Library is a bibliographic database that was created by the MiP Consortium in 2005 and is updated every four months using a standardized search protocol. A bibliometric review was conducted of the contents of the Library to determine dynamics in the type, content and volume of literature on malaria in pregnancy over time.
Data on year of publication, type, language, country of first-author affiliation and content (topic) were extracted from entries in the MiP Library and plotted over time.
By January 2012, the MiP Library contained 5,346 entries, consisting of 3,721 journal articles (69.6%), 697 reports (13.0%), 219 academic theses (4.1%), 92 books or book chapters (1.7%), 487 conference proceedings (9.1%), 68 registered studies (1.3%) and 62 ‘other’ (1.2%). Most of the sources were in English language (87.3%), followed by French (7.5%) and Spanish (1.5%). Over 40% of source material was publicly available online (42.4%) and the remaining with restricted access (35.0%) or otherwise unavailable (22.7%). The number of journal articles related to malaria in pregnancy increased from 41 in the 1960s, to 708 in the 1990s, and 1,895 between 2000 and 2009, and the variety of themes has increased over time. English-language articles were sourced from 737 different journals. The top three journals were the American Journal of Tropical Medicine and Hygiene (184), Malaria Journal (158) and the Transactions of the Royal Society of Tropical Medicine and Hygiene (131).
The last decade has seen a dramatic increase in publications related to malaria in pregnancy, and an increasing proportion of these are publically available online. The MiP Library is a useful, scholarly source for literature and systematic reviews related to malaria in pregnancy.
PMCID: PMC3522037  PMID: 23110589
Malaria; Pregnancy; Bibliometrics
15.  Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States 
PLoS Medicine  2013;10(8):e1001500.
Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties.
Methods and Findings
We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies.
Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating “pre-disease”; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes.
Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications.
For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies.
Please see later in the article for the Editors' Summary
Editors' Summary
Health professionals generally base their diagnosis of physical and mental disorders among their patients on disease definitions and diagnostic thresholds that are drawn up by expert panels and published as statements or as part of clinical practice guidelines. These disease definitions and diagnostic thresholds are reviewed and updated in response to changes in disease detection methods, treatments, medical knowledge, and, in the case of mental illness, changes in cultural norms. Sometimes, the review process widens disease definitions and lowers diagnostic thresholds. Such changes can be beneficial. For example, they might ensure that life-threatening conditions are diagnosed early when they are still treatable. But the widening of disease definitions can also lead to over-diagnosis—the diagnosis of a condition in a healthy individual that will never cause any symptoms and won't lead to an early death. Over-diagnosis can unnecessarily label people as ill, harm healthy individuals by exposing them to treatments they do not need, and waste resources that could be used to treat or prevent “genuine” illness.
Why Was This Study Done?
In recent years, evidence for widespread financial and non-financial ties between pharmaceutical companies and the health professionals involved in writing clinical practice guidelines has increased, and concern that these links may influence professional judgments has grown. As a result, a 2011 report from the US Institute of Medicine (IOM) recommended that, whenever possible, guideline developers should not have conflicts of interest, that a minority of the panel members involved in guideline development should have conflicts of interest, and that the chairs of these panels should be free of conflicts. Much less is known, however, about the ties between industry and the health professionals involved in reviewing disease definitions and whether these ties might in some way contribute to over-diagnosis. In this cross-sectional study (an investigation that takes a snapshot of a situation at a single time point), the researchers identify panels that have recently made decisions about definitions or diagnostic thresholds for conditions that are common in the US and describe the industry ties among the panel members and the changes in disease definitions proposed by the panels.
What Did the Researchers Do and Find?
The researchers identified 16 publications in which expert panels proposed changes to the disease definitions and diagnostic criteria for 14 conditions that are common in the US such as hypertension (high blood pressure) and Alzheimer disease. The proposed changes widened the disease definition for ten diseases, narrowed it for one disease, and had an unclear impact for five diseases. Reasons included in the publications for changing disease definitions included new evidence of risk for people previously considered normal (pre-hypertension) and the emergence of new biomarkers, tests, or treatments (Alzheimer disease). Only six of the panels mentioned possible harms of the proposed changes and none appeared to rigorously assess the downsides of expanding definitions. Of the 15 panels involved in the publications (one panel produced two publications), 12 included members who disclosed financial ties to multiple companies. Notably, the commonest industrial ties among these panels were to companies marketing drugs for the disease being considered by that panel. On average, 75% of panel members disclosed industry ties (range 0% to 100%) to a median of seven companies each. Moreover, similar proportions of panel members disclosed industry ties in publications released before and after the 2011 IOM report.
What Do These Findings Mean?
These findings show that, for the conditions studied, most panels considering disease definitions and diagnostic criteria proposed changes that widened disease definitions and that financial ties with pharmaceutical companies with direct interests in the therapeutic area covered by the panel were common among panel members. Because this study does not include a comparison group, these findings do not establish a causal link between industry ties and proposals to change disease definitions. Moreover, because the study concentrates on a subset of common diseases in the US setting, the generalizability of these findings is limited. Despite these and other study limitations, these findings provide new information about the ties between industry and influential medical professionals and raise questions about the current processes of disease definition. Future research, the researchers suggest, should investigate how disease definitions change over time, how much money panel members receive from industry, and how panel proposals affect the potential market of sponsors. Finally it should aim to design new processes for reviewing disease definitions that are free from potential conflicts of interest.
Additional Information
Please access these Web sites via the online version of this summary at
A PLOS Medicine Research Article by Knüppel et al. assesses the representation of ethical issues in general clinical practice guidelines on dementia care
Wikipedia has a page on medical diagnosis (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
An article on over-diagnosis by two of the study authors is available; an international conference on preventing over-diagnosis will take place this September
The 2011 US Institute of Medicine report Clinical Practice Guidelines We Can Trust is available
A PLOS Medicine Essay by Lisa Cosgrove and Sheldon Krimsky discusses the financial ties with industry of panel members involved in the preparation of the latest revision of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM), which provides standard criteria for the classification of mental disorders
PMCID: PMC3742441  PMID: 23966841
16.  Examining urban brownfields through the public health "macroscope". 
Environmental Health Perspectives  2002;110(Suppl 2):183-193.
Efforts to cope with the legacy of our industrial cities--blight, poverty, environmental degradation, ailing communities--have galvanized action across the public and private sectors to move vacant industrial land, also referred to as brownfields, to productive use; to curb sprawling development outside urban areas; and to reinvigorate urban communities. Such efforts, however, may be proceeding without thorough investigations into the environmental health and safety risks associated with industrial brownfields properties and the needs of affected neighborhoods. We describe an approach to characterize vacant and underused industrial and commercial properties in Southeast Baltimore and the health and well being of communities living near these properties. The screening algorithm developed to score and rank properties in Southeast Baltimore (n= 182) showed that these sites are not benign. The historical data revealed a range of hazardous operations, including metal smelting, oil refining, warehousing, and transportation, as well as paints, plastics, and metals manufacturing. The data also identified hazardous substances linked to these properties, including heavy metals, solvents, polycyclic aromatic hydrocarbons, plasticizers, and insecticides, all of which are suspected or recognized toxicants and many of which are persistent in the environment. The health analysis revealed disparities across Southeast Baltimore communities, including excess deaths from respiratory illness (lung cancer, chronic obstructive pulmonary disease, influenza, and pneumonia), total cancers, and a "leading cause of death" index and a spatial and statistical relationship between environmentally degraded brownfields areas and at-risk communities. Brownfields redevelopment is a key component of our national efforts to address environmental justice and health disparities across urban communities and is critical to urban revitalization. Incorporating public health into brownfields-related cleanup and land-use decisions will increase the odds for successful neighborhood redevelopment and long-term public health benefits.
PMCID: PMC1241162  PMID: 11929727
17.  An observational study of the proceedings of the All India Ophthalmological Conference, 2000 and subsequent publication in indexed journals 
Indian Journal of Ophthalmology  2008;56(3):189-195.
To determine the quality of reporting in the proceedings of the All India Ophthalmological Conference (AIOC) 2000, subsequent rate of publication in an indexed journal and differences between the proceedings and the journal version of these papers.
Observational study.
Materials and Methods:
All papers presented at the AIOC 2000 were retrieved from the proceedings and assessed for completeness of reporting. To determine the subsequent full publication, a Medline search was performed as of January 2007; consistency between the proceedings paper and the final publication was evaluated. Statistical analysis: Chi square and Fisher′s exact tests were used to compare publication rates based on geographical location, subspecialty and study design; Student′s t-test was used to compare differences based on the number of authors and sample size.
Two hundred papers were retrieved; many failed to include study dates, design or statistical methods employed. Thirty-three (16.5%) papers were subsequently published in indexed journals by January 2007. The published version differed from the proceedings paper in 27 (81.8%) instances, mostly relating to changes in author name, number or sequence.
The overall quality of reporting of scientific papers in the proceedings of the AIOC 2000 was inadequate and many did not result in publication in an indexed journal. Differences between the published paper in journals and in proceedings were seen in several instances. Ophthalmologists should be cautious about using the information provided in conference proceedings in their ophthalmic practice.
PMCID: PMC2636100  PMID: 18417818
All India ophthalmological conference proceedings; indexed journal; ophthalmology; publication rates
18.  Final report of the Conference on the eradicability of Onchocerciasis 
Filaria Journal  2003;2:2.
Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24.
The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of onchocerciasis (REMO) and Geographic Information Systems (GIS). In the Americas, through support of the Onchocerciasis Elimination Program in the Americas (OEPA), a strategy of bi-annual ivermectin treatment of at least 85% of the eligible populations in all endemic communities is showing very good results and promises to be effective in eliminating onchocerciasis in the region.The Conference concluded that onchocerciasis is not eradicable using current tools due to the major barriers to eradication in Africa. However, the Conference also concluded that in most if not all the Americas, and possibly Yemen and some sites in Africa, transmission of onchocerciasis can be eliminated using current tools. The Conference recommended that where interruption of transmission is feasible and cost effective, programs should aim for that goal using all appropriate and available interventions so that the Onchocerca volvulus can eventually be eliminated and interventions halted. Although interruption of transmission of onchocerciasis cannot currently be achieved in most of Africa, the Conference recommended that efforts be made to preserve areas in West Africa made free of onchocerciasis transmission through the Onchocerciasis Control Program over the past 25 years. In the remaining hyper and mesoendemic foci in Africa, continued annual distribution of ivermectin will keep onchocerciasis controlled to a point where it is no longer a public health problem or constraint to economic development.
PMCID: PMC150378  PMID: 12605722
19.  Gender Differences in Determinants and Consequences of Health and Illness 
This paper uses a framework developed for gender and tropical diseases for the analysis of non-communicable diseases and conditions in developing and industrialized countries. The framework illustrates that gender interacts with the social, economic and biological determinants and consequences of tropical diseases to create different health outcomes for males and females. Whereas the framework was previously limited to developing countries where tropical infectious diseases are more prevalent, the present paper demonstrates that gender has an important effect on the determinants and consequences of health and illness in industrialized countries as well. This paper reviews a large number of studies on the interaction between gender and the determinants and consequences of chronic diseases and shows how these interactions result in different approaches to prevention, treatment, and coping with illness. Specific examples of chronic diseases are discussed in each section with respect to both developing and industrialized countries.
PMCID: PMC3013263  PMID: 17615903
Gender identity; Health; Tropical medicine; Developing countries; Developed countries; Chronic disease; Impact studies; Review literature
20.  Control of neglected tropical diseases needs a long-term commitment 
BMC Medicine  2010;8:67.
Neglected tropical diseases are widespread, particularly in sub-Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma), using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy.
Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long-term sustainable control of these diseases requires: (1) a long-term commitment from a wider range of donors and from governments of endemic countries; (2) close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3) concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross-border disease transmission; (4) comprehensive control measures for certain diseases; and (5) strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes.
The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be supported through the current major funding streams in order to achieve the objectives of the control of these diseases. For a long-term and sustainable effort, control of neglected tropical diseases should also be integrated into national primary healthcare systems.
PMCID: PMC2987894  PMID: 21034473
21.  Tobacco control implications of the first European product liability suit 
Tobacco Control  2005;14(1):22-30.
Objective: To examine tobacco control implication of the first European product liability suit in Finland.
Methods: Systematic search of internal tobacco industry documents available on the internet and at the British American Tobacco Guildford Depository.
Results: Despite legal loss, the litigation contributed to subsequent tobacco control legislation in Finland. The proceedings revealed that the industry had concealed the health hazards of its products and, despite indisputable evidence, continued to deny them. The positions taken by the industry rocked its reliability as a social actor and thus weakened its chances of influencing tobacco policy. Despite fierce opposition from the tobacco industry, tobacco products were included in the product liability legislation, tobacco was entered on the Finnish list of carcinogens, and an extensive Tobacco Act was passed in Parliament.
Conclusions: Tobacco litigation might not stand alone as a tool for public health policymaking but it may well stimulate national debate over the role of smoking in society and influence the policy agenda.
PMCID: PMC1747990  PMID: 15735296
22.  Blood Clotting Factor VIII: From Evolution to Therapy 
Acta Naturae  2013;5(2):19-39.
Recombinant blood clotting factor VIII is one of the most complex proteins for industrial manufacturing due to the low efficiency of its gene transcription, massive intracellular loss of its proprotein during post-translational processing, and the instability of the secreted protein. Improvement in hemophilia A therapy requires a steady increase in the production of factor VIII drugs despite tightening standards of product quality and viral safety. More efficient systems for heterologous expression of factor VIII can be created on the basis of the discovered properties of its gene transcription, post-translational processing, and behavior in the bloodstream. The present review describes the deletion variants of factor VIII protein with increased secretion efficiency and the prospects for the pharmaceutical development of longer acting variants and derivatives of factor VIII.
PMCID: PMC3695351  PMID: 23819034
blood clotting factor VIII; hemophilia A; heterologous protein expression systems
23.  Community-Based Partnered Research: New Directions in Mental Health Services Research 
Ethnicity & disease  2011;21(3 0 1):S1-8-16.
Community-based participatory research has the potential to improve implementation of best practices to reduce disparities but has seldom been applied in mental health services research. This article presents the content and lessons learned from a national conference designed to stimulate such an application.
Mental health program developers collaborated in hosting a two-day conference that included plenary and break-out sessions, sharing approaches to community-academic partnership development, and preliminary findings from partnered research studies. Sessions were audiotaped, transcribed and analyzed by teams of academic and community conference participants to identify themes about best practices, challenges faced in partnered research, and recommendations for development of the field. Themes were illustrated with selections from project descriptions at the conference.
Setting and Participants
Participants, representing 9 academic institutions and 12 community-based agencies from four US census regions, were academic and community partners from five research centers funded by the National Institute of Mental Health, and also included staff from federal and non-profit funding agencies.
Five themes emerged: 1) Partnership Building; 2) Implementing and Supporting Partnered Research; 3) Developing Creative Dissemination Strategies; 4) Evaluating Impact; and 5) Training.
Emerging knowledge of the factors in the partnership process can enhance uptake of new interventions in mental health services. Conference proceedings suggested that further development of this field may hold promise for improved approaches to address the mental health services quality chasm and service disparities.
PMCID: PMC3653438  PMID: 22352075
Community-Based Partnered Research; Mental Health; Disparities; Implementation; Dissemination
24.  A Premiere example of the illusion of harm reduction cigarettes in the 1990s 
Tobacco Control  2003;12(3):322-332.
Objective: To use the product launch of Player's Premiere as a case study for understanding the new cigarette product development process during the 1990s. We determine the (in)validity of industry claims that: (1) development of the physical product preceded the promotional promise of "less irritation"; (2) "less irritation" was actually realised; (3) advertising informed consumers; and (4) advertising regulations caused the product's failure in the marketplace.
Setting: Court proceedings assessing the constitutionality of Canada's Tobacco Act, which substantially restricts cigarette advertising. The 2002 Quebec Superior Court trial yielded a new collection of internal documents from Imperial Tobacco Ltd (ITL), including several about the development and marketing of Player's Premiere.
Method: Trial testimony and corporate documents were reviewed to determine the validity of the industry representations about the new cigarette product development process, focusing on the case history of Player's Premiere.
Results: In direct contradiction to industry testimony, the documentary evidence demonstrates that (1) communications for Player's Premiere, which claimed less irritation, were developed long before finding a product that could deliver on the promise; (2) ITL did not sell a "less irritating" product that matched its promotional promise; (3) the advertising and other communications for Player's Premiere were extensive, relying on the hi-tech appearances ("tangible credibility") of a "unique" filter, yet were uninformative and vague; and (4) Player's Premiere failed in the marketplace, despite extensive advertising and retail support, because it was an inferior product that did not live up to its promotional promise, not because of regulation of commercial speech.
Conclusions: New product development entails extensive consumer research to craft all communications tools in fine detail. In the case of Player's Premiere, this crafting created a false and misleading impression of technological advances producing a "less irritating" cigarette. This product was solely a massive marketing ploy with neither consumer benefits, nor public health benefits. The industry attempted to deceive both consumers and the court.
PMCID: PMC1747759  PMID: 12958396
25.  From bench to clinic and back: Perspective on the 1st IQPC Translational Research conference 
Translational Research (TR) provides a set of tools and communication context for scientists and clinicians to optimize the drug discovery and development process. In the proceedings of a Princeton conference on this timely topic, the strengths and needs of this developing field were debated. Outcomes and key points from these discussions are summarized in this article which covers the topics of defining what we mean by translational research (both theoretically and in operational terms), ways in which to engender the TR mindset and embed it in organizations such as the pharmaceutical industry in order to optimize the impact of available technologies (including imaging methods), the scientific basis and under-pinnings of TR including genomics knowledge, information sharing, as well as examples of application to drug discovery and development. Importantly, it should be noted that collaborations and communications between the stakeholders in this field, namely academia, industry and regulatory authorities, must be strengthened in order for the promise of TR to be delivered as better therapies to patients.
PMCID: PMC544857  PMID: 15610560

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