Department of defense R & d in the university.

The DOD carefully evaluates its technical needs and executes programs of sponsored research and development to fulfill them. Thus, while individual projects proceed in accordance with established scientific principles of objectivity, the overall system of DOD funding allows the military to influence the development of science technology. Many have argued that this system of contracts and grants has well served science and the universities. One cannot deny that the influx of money led to rapid progress in selected scientific fields and increased scientific institutions' affluence. With this fact we have no quarrel. However, these same people often continue to argue that the systems of federal funding for science, specifically DOD funding of science, follows merely on the work's scientific merit, not on how it fits any larger scheme. They continue, that, since DOD supports good science for its own sake, the combination of military money and universities strongly encouraging faculty to seek that money encourages healthy competition for faster scientific progress. The DOD's approval process is seen to follow from the scientist up, with the military deciding which proposals for research have the most intrinsic (scientific) merit, then after the fact, thinking up a military justification for congressional budget requests. It is this latter belief with which we take issue. The DOD considers the scientific worth of the proposals for research it receives, but only after it has determined that the proposal fulfills a specific military need. This fact and its implications for the university as an institution charged with protecting the process by which man discovers new knowledge have been ignored in the debates over DOD sponsored research and development in universities. In addition, the Nixon Administration's efforts to tighten management controls over civilian research, especially in the biomedical and energy areas, promises to further undermine the university's role as an institution charged with fostering a search for truth free from bias in both methodology and subject selection.

Enacting tobacco taxes by direct popular vote in the United States: lessons from 20 years of experience.

BACKGROUND: Tobacco tax increases reduce tobacco use, can provide funds for tobacco prevention and enjoy broad public support. Because of tobacco industry influence in legislatures, US public health advocates have shifted the venue for tobacco tax policymaking to direct popular vote 22 times since 1988. METHODS: We combined case studies of individual state campaigns with tobacco industry documents to identify strategies related to outcome. RESULTS: The tobacco industry developed a voter segmentation model to determine which tobacco tax increases it could defeat. Two industry arguments arising from this model often were raised in losing campaigns-the tax increase did not dedicate enough to tobacco control and hospitals and health maintenance organisations would profit. The industry effectively influenced early voters. Success was associated with building a strong base of public support before the campaign, dedicating sufficient funds to tobacco control, avoiding proposals largely devoted to financing hospitals and other medical service providers, effectively engaging grassroots and framing the campaign with clear justifications for cigarette tax increases. CONCLUSIONS: Tobacco tax ballot measures commonly allocated substantial funds to medical services; tobacco companies are becoming more successful in making this use of funds an issue. Proponents' campaigns should be timed to account for the trend to voting well before election day. Ballot measures to increase tobacco taxes with a substantial fraction of the money devoted to tobacco control activities will probably fare better than ones that give priority to funding medical services.

Signed, sealed and delivered: "big tobacco" in Hollywood, 1927-1951.

OBJECTIVE: Smoking in movies is associated with adolescent and young adult smoking initiation. Public health efforts to eliminate smoking from films accessible to youth have been countered by defenders of the status quo, who associate tobacco imagery in "classic" movies with artistry and nostalgia. The present work explores the mutually beneficial commercial collaborations between the tobacco companies and major motion picture studios from the late 1920s through the 1940s. METHODS: Cigarette endorsement contracts with Hollywood stars and movie studios were obtained from internal tobacco industry documents at the University of California, San Francisco (UCSF) Legacy Tobacco Documents Library and the Jackler advertising collection at Stanford. RESULTS: Cigarette advertising campaigns that included Hollywood endorsements appeared from 1927 to 1951, with major activity in 1931-2 and 1937-8 for American Tobacco Company's Lucky Strike, and in the late 1940s for Liggett & Myers' Chesterfield. Endorsement contracts and communication between American Tobacco and movie stars and studios explicitly reveal the cross-promotional value of the campaigns. American Tobacco paid movie stars who endorsed Lucky Strike cigarettes US$218,750 in 1937-8 (equivalent to US$3.2 million in 2008) for their testimonials. CONCLUSIONS: Hollywood endorsements in cigarette advertising afforded motion picture studios nationwide publicity supported by the tobacco industry's multimillion US dollar advertising budgets. Cross-promotion was the incentive that led to a synergistic relationship between the US tobacco and motion picture industries, whose artefacts, including "classic" films with smoking and glamorous publicity images with cigarettes, continue to perpetuate public tolerance of onscreen smoking. Market-based disincentives within the film industry may be a solution to decouple the historical association between Hollywood films and cigarettes.

cAMP signaling in neurons: patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase II beta.

In mammalian brain, physiological signals carried by cyclic AMP (cAMP) seem to be targeted to effector sites via the tethering of cAMP-dependent protein kinase II beta (PKAII beta) to intracellular structures. Recently characterized A kinase anchor proteins (AKAPs) are probable mediators of the sequestration of PKAII beta because they contain a high-affinity binding site for the regulatory subunit (RII beta) of the kinase and a distinct intracellular targeting domain. To establish a cellular basis for this targeting mechanism, we have employed immunocytochemistry to 1) identify the types of neurons that are enriched in AKAPs, 2) determine the primary intracellular location of the anchor protein, and 3) demonstrate that an AKAP and RII beta are coenriched and colocalized in neurons that utilize the adenylate cyclase-cyclic AMP-dependent protein kinase (PKA) signaling pathway. Antibodies directed against rat brain AKAP 150 were used to elucidate the regional, cellular and intracellular distribution of a prototypic anchor protein in the CNS. AKAP 150 is abundant in Purkinje cells and in neurons of the olfactory bulb, basal ganglia, cerebral cortex, and other forebrain regions. In contrast, little AKAP 150 is detected in neurons of the thalamus, hypothalamus, midbrain, and hindbrain. A high proportion of total AKAP 150 is concentrated in primary branches of dendrites, where it is associated with microtubules. We also discovered that the patterns of accumulation and localization of RII beta (and PKAII beta) in brain are similar to those of AKAP 150. The results suggest that bifunctional AKAP 150 tethers PKAII beta to the dendritic cytoskeleton, thereby creating a discrete target site for the reception and propagation of signals carried by cAMP.

German tobacco industry's successful efforts to maintain scientific and political respectability to prevent regulation of secondhand smoke.

OBJECTIVE: To examine the tactics the tobacco industry in Germany used to avoid regulation of secondhand smoke exposure and to maintain the acceptance of public smoking. METHODS: Systematic search of tobacco industry documents available on the internet between June 2003 and August 2004. RESULTS: In West Germany, policymakers were, as early as the mid 1970s, well aware of the fact that secondhand smoke endangers non-smokers. One might have assumed that Germany, an international leader in environmental protection, would have led in protecting her citizens against secondhand smoke pollution. The tobacco manufacturers in Germany, however, represented by the national manufacturing organisation "Verband" (Verband der Cigarettenindustrie), contained and neutralised the early debate about the danger of secondhand smoke. This success was achieved by carefully planned collaboration with selected scientists, health professionals and policymakers, along with a sophisticated public relations programme. CONCLUSIONS: The strategies of the tobacco industry have been largely successful in inhibiting the regulation of secondhand smoke in Germany. Policymakers, health professionals, the media and the general public should be aware of this industry involvement and should take appropriate steps to close the gap between what is known and what is done about the health effects of secondhand smoke.

Eliminating child labour in Malawi: a British American Tobacco corporate responsibility project to sidestep tobacco labour exploitation.

OBJECTIVES: To examine British American Tobacco and other tobacco industry support of the Eliminating Child Labour in Tobacco Growing Foundation. DESIGN: Analyses of internal tobacco industry documents and ethnographic data. RESULTS: British American Tobacco co-founded the Eliminating Child Labour in Tobacco Growing Foundation (ECLT) in October 2000 and launched its pilot project in Malawi. ECLT's initial projects were budgeted at US2.3 million dollars over four years. Labour unions and leaf dealers, through ECLT funds, have undertook modest efforts such as building schools, planting trees, and constructing shallow wells to address the use of child labour in tobacco farming. In stark contrast, the tobacco companies receive nearly US40 million dollars over four years in economic benefit through the use of unpaid child labour in Malawi during the same time. BAT's efforts to combat child labour in Malawi through ECLT was developed to support the company's "corporate social responsibility agenda" rather than accepting responsibility for taking meaningful steps to eradicate child labour in the Malawi tobacco sector. CONCLUSION: In Malawi, transnational tobacco companies are using child labour projects to enhance corporate reputations and distract public attention from how they profit from low wages and cheap tobacco.

Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function.

BACKGROUND: Determinants of left atrial (LA) reservoir function and its influence on left ventricular (LV) function have not been quantified. METHODS AND RESULTS: In an open-pericardium, paced (70 and 90 bpm) pig model of LV regional ischemia (left anterior descending coronary constriction), with high-fidelity LV, LA, and RV pressure recordings, we obtained the LA area with 2D automated border detection echocardiography, LA pressure-area loops, and Doppler transmitral flow. We calculated LV tau, LA relaxation (a-x pressure difference divided by time, normalized by a pressure), and stiffness (slope between x and v pressure points of v loop). Determinants of total LA reservoir (maximum-minimum area, cm(2)) were identified by multiple regression analysis. Different mean rates of LA area increase identified 2 consecutive (early rapid and late slow) reservoir phases. During ischemia, LV long-axis shortening (LAS, LV base systolic descent) and LA reservoir area change decreased (7.3+/-0.3 [SEM] versus 5.6+/-0.3 cm(2), P<0.001) and LA stiffness increased (1.6+/-0.3 versus 3.1+/-0.3 mm Hg/cm(2), P=0.009). Early reservoir area change depended on LA mean ejection rate (LA area at ECG P wave minus minimum area divided by time; multiple regression coefficient=0.9; P<0.001) and relaxation (coefficient=4.9 cm(2)xms/s; P<0.001). Late reservoir area change depended on LAS (coefficient=8 cm/s; P<0.001). Total reservoir filling depended on LA stiffness (coefficient=-0.31 cm(4)/mm Hg; P=0. 001) and cardiac output (coefficient=0.001 cm(2)xmin/L; P=0.002). The strongest predictor of cardiac output was LA reservoir filling (coefficient=301 L/minxcm(2); P<0.001). The v loop area was determined by cardiac output, LV ejection time, tau, and early transmitral flow. CONCLUSIONS: Two (early and late) reservoir phases are determined by LA contraction and relaxation and LV base descent. Acute LV regional ischemia increases LA stiffness and impairs LA reservoir function by reducing LV base descent.

Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Changes in porcine transmitral flow velocity pattern and its diastolic determinants during partial coronary occlusion.

OBJECTIVES: To define the mechanical determinants of transmitral flow and the effect of heart rate during regional ischemia. BACKGROUND: Myocardial ischemia changes the transmitral flow velocity pattern due to disease-induced changes in the heart's diastolic properties. METHODS: Regional ischemia was produced in 12 pigs by partially occluding the left anterior descending coronary artery until segment-length shortening in the ischemic region fell by 20%. Transmitral flow velocity patterns and their determinants were measured under two conditions, baseline and ischemia, at two heart rates, 70 and 90 beats/min. RESULTS: Regional ischemia had a significant effect on two determinants of filling: relaxation, which was slower, and chamber stiffness, which increased. These changes were associated with reduced contractility and increased myocardial stiffness, resulting in an early transmitral flow pattern that was flatter and narrower, but no change in the late flow pattern. Moderate increases in heart rate accelerated relaxation and decreased atrioventricular pressure gradient but had no effect on contractility or myocardial or chamber stiffness, resulting in an early transmitral flow pattern that was flatter and narrower and an increased late flow velocity. CONCLUSIONS: This model of regional ischemia leads to a flatter and narrower early transmitral flow velocity pattern and no change in late flow due to a combination of slowed left ventricular relaxation and increased chamber stiffness. Reflex increases in heart rate that accompany ischemia tend to mask this effect.

Determinants of forward pulmonary vein flow: an open pericardium pig model.

OBJECTIVE: To elucidate determinants of pulmonary venous (PV) flow. BACKGROUND: Right ventricular (RV) systolic pressure (vis a tergo), left atrial (LA) relaxation and left ventricular (LV) systole and relaxation (vis a fronte) have been suggested as determinants of the pulmonary venous (PV) anterograde Doppler flow velocities, but their relative contributions to those flow velocities have not been quantified. METHODS: We analyzed, by multiple regression analysis, the determinants of PV anterograde velocities in an open-pericardium, paced (70 and 90 beats/min) pig model in which LA afterload was modified by creating LV regional ischemia (left anterior descending coronary artery constriction). We measured high fidelity LA, LV and RV pressures and Doppler flow velocities (epicardial echocardiography). We calculated LV tau, LA relaxation (a through x pressure difference divided by time, normalized by a pressure), LA peak v through x and RV systolic through LA peak v (RVSP-v) pressure differences, LV ejection fraction, long-axis shortening, stroke volume (LV outflow integral x outflow area) and LA four-chamber dimensions, Doppler transmitral and PV flow velocities and velocity-time integrals. RESULTS: Left ventricular regional ischemia increased mildly LA y trough pressure (8 +/- 1 vs. 6 +/- 1 mm Hg, p = 0.001). Left ventricular stroke volume (coefficient: 0.5 cm/ml, SE: 0.2, p = 0.005) and LA peak v pressure (coefficient: -0.8 cm/mm Hg, SE: 0.3, p = 0.008) determined the PV total systolic integral. Left atrial relaxation determined both PV early systolic peak velocity and integral (coefficient: -0.8 cm/mm Hg, SE: 0.3, p = 0.04). Left atrial maximum area (coefficient: 2 cm(-1) SE: 0.7, p = 0.01) and RVSP-v (coefficient: 0.1 cm/mm Hg, SE: 0.05, p = 0.03) determined the late systolic integral. The PV total systolic integral determined both PV early diastolic peak velocity and integral (coefficient: 1.2, SE: 0.2, p = 0.001). CONCLUSIONS: In an experimental model of LV acute ischemia of limited duration, the main independent predictors of PV systolic anterograde flow velocities are LA relaxation and compliance (LA peak v pressure) and LV systole--all vis a fronte factors. In the setting of mildly increased LA pressures, PV systolic flow (LA reservoir filling) is an independent predictor of PV early diastolic flow (LA early conduit).

In-utero and neonatal exposure to secondhand smoke causes vascular dysfunction in newborn rats.

OBJECTIVES: We sought to determine the effects of secondhand smoke (SHS) exposure on vascular reactivity in newborn and infant rats. BACKGROUND: Secondhand smoke exposure increases cardiovascular risk. Secondhand smoke-induced endothelial dysfunction has been demonstrated in older teenagers and young adults. We have previously shown in adult rabbits that SHS induces atherogenesis and endothelial dysfunction. The effects of SHS on vascular function in the offspring of SHS-exposed mothers and in infants are unknown. METHODS: In this study the effects of in-utero (21 days) and neonatal (28 days) exposure to SHS were examined in 80 rats, 4 weeks of age, in a 2-by-2 design study. Rats were exposed to sidestream smoke in smoking chambers. Aortic rings were excised and isometric force responses to phenylephrine, acetylcholine, A23187 and nitroglycerin were studied in organ baths. RESULTS: Neonatal SHS exposure reduced animal weight (p=0.009). In-utero exposure increased the sensitivity (decreased the EC50) of aortic rings to phenylephrine (p < 0.0005), as did neonatal exposure (p=0.01). Maximal contraction to phenylephrine was reduced by in-utero exposure (p=0.04). In-utero SHS exposure reduced maximal endothelium-dependent relaxation to acetylcholine (p=0.04) and increased the EC50 (p=0.05), suggesting impaired sensitivity to acetylcholine. In-utero exposure decreased the sensitivity (increased the EC50) to the endothelium-independent vasodilator nitroglycerin (p=0.003). CONCLUSIONS: Secondhand smoke has detrimental effects on vascular smooth muscle function in the newborn.

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits.

OBJECTIVES: We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits. BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. METHODS: New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry. RESULTS: Average air nicotine, carbon monoxide and total particulate concentrations were 1,040 micrograms/m3, 60.2 ppm and 32.8 mg/m3 for the high dose ETS group, 30 micrograms/m3, 18.8 ppm and 4.0 mg/m3 for the low dose ETS group and < 1 microgram/m3, 3.1 ppm and 0.13 mg/m3 for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increased significantly with ETS exposure (for the aorta, 30 +/- 19% [mean +/- SD] for the control group, 36 +/- 14% for the low dose ETS group and 52 +/- 21% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 +/- 15% for the control group, 29 +/- 25% for the low dose ETS group, and 45 +/- 12% for the high dose ETS group, p < 0.001). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 +/- 17 vs. 68 +/- 15, 68 +/- 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study. CONCLUSIONS: Environmental tobacco smoke affects platelet function and increases aortic and pulmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta.

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.

Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.

OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.

Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke.

BACKGROUND: Exposure to secondhand smoke causes lung cancer; however, there are little data in the open literature on the in vivo toxicology of fresh sidestream cigarette smoke to guide the debate about smoke-free workplaces and public places. OBJECTIVE: To investigate the unpublished in vivo research on sidestream cigarette smoke done by Philip Morris Tobacco Company during the 1980s at its Institut für Biologische Forschung (INBIFO). METHODS: Analysis of internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other websites. RESULTS: Inhaled fresh sidestream cigarette smoke is approximately four times more toxic per gram total particulate matter (TPM) than mainstream cigarette smoke. Sidestream condensate is approximately three times more toxic per gram and two to six times more tumourigenic per gram than mainstream condensate by dermal application. The gas/vapour phase of sidestream smoke is responsible for most of the sensory irritation and respiratory tract epithelium damage. Fresh sidestream smoke inhibits normal weight gain in developing animals. In a 21 day exposure, fresh sidestream smoke can cause damage to the respiratory epithelium at concentrations of 2 microg/l TPM. Damage to the respiratory epithelium increases with longer exposures. The toxicity of whole sidestream smoke is higher than the sum of the toxicities of its major constituents. CONCLUSION: Fresh sidestream smoke at concentrations commonly encountered indoors is well above a 2 microg/m3 reference concentration (the level at which acute effects are unlikely to occur), calculated from the results of the INBIFO studies, that defines acute toxicity to humans. Smoke-free public places and workplaces are the only practical way to protect the public health from the toxins in sidestream smoke.

Tobacco industry consumer research on socially acceptable cigarettes.

OBJECTIVE: To describe tobacco industry consumer research to inform the development of more "socially acceptable" cigarette products since the 1970s. METHODS: Analysis of previously secret tobacco industry documents. RESULTS: 28 projects to develop more socially acceptable cigarettes were identified from Philip Morris, RJ Reynolds, British American Tobacco, and Lorillard tobacco companies. Consumer research and concept testing consistently demonstrated that many smokers feel strong social pressure not to smoke, and this pressure increased with exposure to smoking restrictions. Tobacco companies attempted to develop more socially acceptable cigarettes with less visible sidestream smoke or less odour. When presented in theory, these product concepts were very attractive to important segments of the smoking population. However, almost every product developed was unacceptable in actual product tests or test markets. Smokers reported the complete elimination of secondhand smoke was necessary to satisfy non-smokers. Smokers have also been generally unwilling to sacrifice their own smoking satisfaction for the benefit of others. Many smokers prefer smoke-free environments to cigarettes that produce less secondhand smoke. CONCLUSIONS: Concerns about secondhand smoke and clean indoor air policies have a powerful effect on the social acceptability of smoking. Historically, the tobacco industry has been unable to counter these effects by developing more socially acceptable cigarettes. These data suggest that educating smokers about the health dangers of secondhand smoke and promoting clean indoor air policies has been difficult for the tobacco industry to counter with new products, and that every effort should be made to pursue these strategies.

The limits of competing interest disclosures.

OBJECTIVE: To assess the effectiveness of conflict of interest disclosure policies by comparing a competing interests disclosure statement that met the requirements established by the journal in a 2003 article on health effects of secondhand smoke based on the American Cancer Society CPS-I dataset with internal tobacco industry documents describing financial ties between the tobacco industry and authors of the study. DESIGN: Descriptive analysis of internal tobacco industry documents retrieved from the Legacy Tobacco Documents Library, University of California, San Francisco. RESULTS: Meeting the requirements for financial disclosure established by the journal did not provide the reader with a full picture of the tobacco industry's involvement with the study authors. The tobacco industry documents reveal that the authors had long standing financial and other working relationships with the tobacco industry. CONCLUSION: These findings are another example of how simply requiring authors to disclose financial ties with the tobacco industry may not be adequate to give readers (and reviewers) a full picture of the author's relationship with the tobacco industry. The documents also reveal that the industry funds research to enhance its credibility and endeavours to work with respected scientists to advance its goals. These findings question the adequacy of current journal policies regarding competing interest disclosures and the acceptability of tobacco industry funding for academic research.

Tobacco industry influence on the definition of tobacco related disorders by the American Psychiatric Association.

OBJECTIVE: The Diagnostic and statistical manual of mental disorders, third edition (DSM-III), published by the American Psychiatric Association (APA) in 1980, included the first official definitions by the APA of tobacco dependence and tobacco withdrawal. Tobacco industry efforts to influence the DSM-III were investigated. METHOD: Searches of previously secret tobacco industry documents, primarily the University of California San Francisco Legacy Tobacco Documents Library and British American Tobacco collections. Additional information was collected through discussions with editors of DSM-III, and library and general internet searches. RESULTS: The tobacco companies regarded the inclusion of tobacco dependence as a diagnosis in DSM-III as an adverse event. It worked to influence the content of the DSM-III and its impact following publication. These efforts included public statements and private lobbying of DSM-III editors and high ranking APA officers by prominent US psychiatrists with undisclosed ties to the tobacco industry. Following publication of DSM-III, tobacco companies contracted with two US professors of psychiatry to organise a conference and publish a monograph detailing controversies surrounding DSM-III. CONCLUSIONS: The tobacco industry and its allies lobbied to narrow the definition of tobacco dependence in serial revisions of DSM-III. Following publication of DSM-III, the industry took steps to try to mitigate its impact. These actions mirror industry tactics to influence medical research and policy in various contexts worldwide. Such tactics slow the spread of a professional and public understanding of smoking and health that otherwise would reduce smoking, smoking induced disease, and tobacco company profits.

Smoke-free law did not affect revenue from gaming in Delaware.

OBJECTIVE: To determine the effect of the Delaware smoke-free law on gaming revenue. METHODS: Linear regression of gaming revenue and average revenue per machine on a public policy variable, time, while controlling for economic activity and seasonal effects. RESULTS: The linear regression showed that the smoke-free law was associated with no effect on total revenue or average revenue per machine. CONCLUSION: Smoke-free laws are associated with no change in gaming revenue.

Emotions for sale: cigarette advertising and women's psychosocial needs.

OBJECTIVE: To explore messages of psychosocial needs satisfaction in cigarette advertising targeting women and implications for tobacco control policy. METHODS: Analysis of internal tobacco industry documents and public advertising collections. RESULTS: Tobacco industry market research attempted to identify the psychosocial needs of different groups of women, and cigarette advertising campaigns for brands that women smoke explicitly aimed to position cigarettes as capable of satisfying these needs. Such positioning can be accomplished with advertising that downplays or excludes smoking imagery. As women's needs change with age and over time, advertisements were developed to reflect the needs encountered at different stages in women's lives. Cigarette brands for younger women stressed female camaraderie, self confidence, freedom, and independence; cigarette brands for older women addressed needs for pleasure, relaxation, social acceptability, and escape from daily stresses. CONCLUSIONS: Psychosocial needs satisfaction can be communicated without reference to cigarettes or smoking. This may explain why partial advertising bans are ineffective and comprehensive bans on all forms of tobacco marketing are effective. Counter-advertising should attempt to expose and undermine the needs satisfaction messages of cigarette advertising campaigns directed at women.