This is the first controlled prospective study of the effects of nicotine deprivation in adolescent smokers. Heart rate and subjective withdrawal symptoms were measured over an 8-hr period while participants smoked normally. Seven days later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or a placebo patch for 8 hr, and they refrained from smoking during the session. Those wearing the placebo experienced a decrease in heart rate across sessions and an increase in subjective measures of nicotine withdrawal. Those wearing the active patch also reported significant increases for some subjective symptoms. Expectancy effects were also observed. The findings indicate that adolescent smokers experience subjective and objective changes when deprived of nicotine. As in previous research with adults, expectancies concerning the effects of nicotine replacement also influenced perceptions of withdrawal.

The horrifying events of 11 September 2001 serve notice that civilization will confront severe challenges in the twenty-first century. As national security budgets expand in response, we should recognize that only a broad conception of security will be adequate to meet some of the threats that we may face. Biological security provides a powerful example. It must address both the challenge of biological weapons and that of infectious disease. The right approach should benefit public health even if major acts of biological terrorism never occur. Our thinking about biological security must transcend old misplaced analogies to nuclear and chemical security.

Nuclear security has been based on nonproliferation, deterrence, and defense, with intelligence woven throughout. Nonproliferation seeks to prevent the diversion of materials from civilian programs to military or terrorist weapons. Should nonproliferation fail, the United States relies on deterrence through the threat of retaliation. Defense, active or civil, has so far been less central.

Effective biological security requires a different mix. For all its challenges, nuclear nonproliferation is comparatively robust, in part because the production of weapons-usable uranium or plutonium provides a conspicuous bottleneck through which any nuclear program must pass, unless those materials are stolen. This is why preventing nuclear theft is such a high priority in the post-Cold War world. Biological agents

are easier to acquire. Most can be found in naturally occurring outbreaks. Weaponizing these agents has proved challenging for terrorist groups, but the Aum Shinrikyo's unsuccessful efforts to spray the anthrax organism throughout Tokyo in 1993 warned that attempted mass urban attacks were no longer in the realm of the fantastic.

The transfer of dangerous biological agents should be controlled where possible, and the spread of the technologies and personnel to weaponize them should be impeded. But any biological nonproliferation regime will necessarily be less robust than its nuclear counterpart, because the relevant materials, technologies, and knowledge are far more widespread.

Biological terrorism also challenges requirements for successful deterrence. Because some diseases incubate for a week or more, identifying the perpetrators of an attack may prove difficult. A terrorist group might even hope that its attack would go unrecognized; when followers of the Bhagwan Shree Rajneesh infected 750 Oregonians with salmonella in 1984, it took over a year before the infection was determined to have been intentional. Finally, as with any form of terrorism, some groups may simply be unconcerned about retaliation.

In the face of these difficulties, good intelligence is all the more important. Warning and prevention are preferable to coping with the consequences of an attack, but we must also be ready should an attack occur. This requires that greater emphasis be placed on improving public health, a kind of homeland defense that is applicable to both unintentional and intentional disease outbreaks.

Because of disease incubation times, the first responders to a biological attack may well be health-care workers at hospitals and clinics rather than specialized units. The speed and effectiveness of a response will depend on disease surveillance: the recognition by health-care workers that certain illnesses appear unusual and the rapid notification of the proper authorities. Because incubation times often exceed international travel times, both domestic and international components are required. But the domestic component of disease surveillance in most nations, including the United States, is too weak, and international networks are inadequate. Donor nations need to increase support for these efforts. And there are many other needs, such as developing and stockpiling sufficient vaccines, antibiotics, or antivirals and otherwise preparing to meet the enormous challenges that would be posed by a major outbreak. It is time to quicken the pace of these efforts, to which departments of health are as central as departments of defense.

Disease surveillance and response are not nonproliferation measures, so cannot substitute for an effective verification regime under the Biological Weapons Convention. But biological security requires the developed world, especially the United States, to see that its ongoing self-interest is closely allied with sustainable public-health improvements in the developing world. And the explosion of biotechnology, with the weapons implications that follow from it, requires the scientific community to discuss its responsibilities in earnest.

STANFORD, Calif.- For the past seven years, the United States has been negotiating a verification protocol to the Biological Weapons Convention of 1972, hoping to put teeth into the convention's ban on biological weapons production. The Bush administration recently rejected the latest draft of the protocol, viewing it as irredeemably flawed. This is a good time to ask what a new American strategy should be for security against biological threats. It is difficult to predict the likelihood or scale of biological attack. The right policy will provide benefits whether or not an attack occurs.

The first step is conceptual: we must stop thinking about biological security in the way we think about nuclear security. Few aspects of the United States strategy for nuclear security carry over cleanly to the biological case. Security against nuclear attack has relied upon nonproliferation and deterrence, with comparatively little role, so far, for defense. Security against biological-weapons threats should lean primarily on defense.

Nonproliferation, for example, is far more difficult in the biological case. Biological agents are microscopic organisms that can be grown with equipment readily available all over the world -- although the resulting weapons have proved difficult for terrorists to master. Many of the organisms can be acquired during naturally occurring outbreaks. Controls remain valuable, but they will never play the central role that they do in nuclear security. And as biotechnology explodes in the coming decades, nonproliferation will face ever greater challenges.

Deterrence may likewise be of limited use in preventing attacks with biological weapons. While the use of battlefield biological weapons may be deterred by threats, biological terrorism could remain largely immune. The incubation times of most diseases -- for example, seven to 17 days for smallpox -- may lead terrorists to hope they can cover their tracks through covert releases of biological agents. Deterrence relies on the threat of punishment. An attacker who cannot be identified cannot be threatened.

When the Aum Shinrikyo cultists sprayed an anthrax organism in Tokyo -- they did so unsuccessfully several times before their deadly 1995 nerve-gas attack -- they made no announcements and the attacks went unnoticed. When followers of the Bhagwan Shree Rajneesh infected 750 Oregonians in 1984 with salmonella, it took over a year for the attack to be distinguished from a natural outbreak.

Rather than nonproliferation and deterrence, biological security must emphasize civil defense. Civil defense in the biological realm means improving the public health system. Most important, it requires improving disease surveillance. Unusual disease outbreaks must be recognized quickly, so that a rapid response is possible. Health care workers in clinics, hospitals and private practice must know how to identify such outbreaks and be ready and able to pass their information rapidly to city, state and national authorities.

This kind of preparedness would also help to prevent unintentional outbreaks of disease. Because infected passengers can travel the world in less time than it takes for a disease to incubate, it is crucial, for the national interest as well as for humanitarian reasons, to improve disease surveillance overseas. The United States welcomes 50 million visitors every year and imports $40 billion worth of food. Disease cannot be stopped at the border. The United States must act internationally as well as nationally.

Because biological security would offer protection against both natural and nefarious transmission of disease, a sound policy would directly benefit society even if no attack ever happened. Effective biological security requires that we fit the cure to the disease.

A biological terrorist attack probably would first be detected by doctors or other health-care workers. The speed of a response would then depend on their rapid recognition and communication that certain illnesses appeared out of the ordinary. For this reason, preparing for biological terrorism has more in common with confronting the threat of emerging infectious diseases than with preparing for chemical or nuclear attacks. Defense against bioterrorism, like protection against emerging diseases, must therefore rely on improved national and international public-health surveillance. Too often, thinking about bioterrorism has mimicked thinking about chemical terrorism, a confusion that leads to an emphasis on the wrong approaches in preparing to meet the threat.

The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.

The associations of cigarette smoking and alcohol consumption with the risk of amyotrophic lateral sclerosis (ALS) were investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and were matched to population controls (n = 321) identified through random digit dialing and Medicare enrollment files. Conditional logistic regression analysis was used to compute odds ratios adjusted for age, gender, respondent type, and education. The authors found that alcohol consumption was not associated with the risk of ALS. Ever having smoked cigarettes was associated with a twofold increase in risk (alcohol-adjusted odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). A greater than threefold increased risk was observed for current smokers (alcohol-adjusted OR = 3.5, 95% CI: 1.9, 6.4), with only a modestly increased risk for former smokers (alcohol-adjusted OR = 1.5, 95% CI: 0.9, 2.4). Significant trends in the risk of ALS were observed with duration of smoking (p for trend = 0.001) and number of cigarette pack-years (p for trend = 0.001). The finding that cigarette smoking is a risk factor for ALS is consistent with current etiologic theories that implicate environmental chemicals and oxidative stress in the pathogenesis of ALS.

OBJECTIVES: This study determined the cost-effectiveness of expanding methadone maintenance treatment for heroin addiction, particularly its effect on the HIV epidemic.

METHODS: We developed a dynamic epidemic model to study the effects of increased methadone maintenance capacity on health care costs and survival, measured as quality-adjusted life-years (QALYs). We considered communities with HIV prevalence among injection drug users of 5% and 40%.

RESULTS: Additional methadone maintenance capacity costs $8200 per QALY gained in the high-prevalence community and $10,900 per QALY gained in the low-prevalence community. More than half of the benefits are gained by individuals who do not inject drugs. Even if the benefits realized by treated and untreated injection drug users are ignored, methadone maintenance expansion costs between $14,100 and $15,200 per QALY gained. Additional capacity remains cost-effective even if it is twice as expensive and half as effective as current methadone maintenance slots.

CONCLUSIONS: Expansion of methadone maintenance is cost-effective on the basis of commonly accepted criteria for medical interventions. Barriers to methadone maintenance deny injection drug users access to a cost-effective intervention that generates significant health benefits for the general population.

BACKGROUND: Cigarette smoking is a major risk factor for several chronic oxidative diseases that can be ameliorated by antioxidants.

OBJECTIVES: This study identified the typical dietary intakes and the major food group contributors of the antioxidants beta-carotene, vitamin C, and vitamin E by smoking status.

DESIGN: The 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) provided the current sample (n = 6749), who were categorized as non- (n = 3231), former (n = 1684), and current (n = 1834) smokers. In the CSFII, individuals' food intakes were estimated with two 24-h dietary recalls. Data were analyzed by using a chi-square test with a simultaneous Fisher's z test, analysis of variance with Scheffe's test, multivariate analysis of covariance, and analysis of covariance with Bonferroni adjustment for multiple comparisons.

RESULTS: The sample consisted of 3707 men and 3042 women. Current smokers tended to be younger with less education and lower incomes than nonsmokers and former smokers. The average body mass index (in kg/m(2)) of current smokers was 25.8, the lowest of the 3 groups. Current smokers had the lowest dietary antioxidant intake. Fatty foods such as luncheon meats, condiments and salad dressings, and ground beef contributed more to the antioxidant intakes of current smokers than to those of the other 2 groups, whereas fruit and vegetables contributed less. Current smokers consumed the fewest numbers of servings of all nutrient-bearing groups in the food guide pyramid, except the meat group.

CONCLUSION: Future interventions should target the clustering of cigarette smoking and other unhealthy lifestyle habits, eg, an imprudent diet.