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Biomedical subjects

Gary J Badger

Publications and source records attributed to Gary J Badger.

At least 19 recordsLinked to original sources

Psychological symptoms following smoking cessation in pregnant smokers.

This study examined the relationship between smoking status and psychological symptoms in pregnant women across pregnancy. Participants were 45 women who quit smoking early in pregnancy (early quitters), 22 who quit later in pregnancy (later quitters), and 84 who smoked throughout pregnancy (never quitters). Assessments of smoking status and psychological symptoms (Brief Symptom Inventory and Beck Depression Inventory) occurred near first prenatal visit, second visit, and end of pregnancy. Results indicated that scores on the Global Severity Index of the Brief Symptom Inventory, several Brief Symptom Inventory subscales, and on the Beck Depression Inventory were highest among never quitters, lowest among early quitters, and intermediate for later quitters. Scores decreased across pregnancy, especially between first and second assessments. We found no evidence that quitting smoking increased psychological symptoms either in the immediate post-withdrawal period or later in pregnancy. These findings should temper concerns that quitting smoking may have detrimental psychological consequences during pregnancy.

Adult↗

Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: evidence for a mechanotransduction-based mechanism.

Acupuncture needle rotation has been previously shown to cause specific mechanical stimulation of subcutaneous connective tissue. This study uses acupuncture to investigate the role of mechanotransduction-based mechanisms in mechanically-induced cytoskeletal remodeling. The effect of acupuncture needle rotation was quantified by morphometric analysis of mouse tissue explants imaged with confocal microscopy. Needle rotation induced extensive fibroblast spreading and lamellipodia formation within 30 min, measurable as an increased in cell body cross sectional area. The effect of rotation peaked with two needle revolutions and decreased with further increases in rotation. Significant effects of rotation were present throughout the tissue, indicating the presence of a response extending laterally over several centimeters. The effect of rotation with two needle revolutions was prevented by pharmacological inhibitors of actomyosin contractility (blebbistatin), Rho kinase (Y-27632 and H-1152), and Rac signaling. The active cytoskeletal response of fibroblasts demonstrated in this study constitutes an important step in understanding cellular mechanotransduction responses to externally applied mechanical stimuli in whole tissue, and supports a previously proposed model for the mechanism of acupuncture involving connective tissue mechanotransduction.

Acupuncture↗

A comparison between low-magnitude voucher and buprenorphine medication contingencies in promoting abstinence from opioids and cocaine.

This study compared the relative efficacy of low-magnitude, contingent monetary vouchers, contingent buprenorphine medication, and standard counseling in promoting abstinence from illicit opioids and cocaine among opioid-dependent adults. Following an 8-week baseline period during which participants received buprenorphine maintenance treatment with no contingencies in place, 60 participants were randomly assigned to one of 3 treatment groups for 12 weeks: (a) Participants in the voucher group earned vouchers for each opioid- and cocaine-negative urine sample, in accordance with an escalating schedule. Continuous abstinence resulted in voucher earnings equivalent to a total of 269 US dollars, which participants could exchange for material reinforcers of their choice. (b) Participants in the medication contingency group received half their scheduled buprenorphine dose for clinic attendance and the other half for remaining abstinent from opiates and cocaine. Thus, they received only half of their scheduled dose on submission of an opioid- and/or cocaine-positive urine sample. (c) Participants in standard treatment did not receive programmed consequences contingent on urinalysis results. All participants were maintained with buprenorphine according to a 3-times-per-week dosing regimen and participated in behavioral drug counseling. Retention rate did not significantly differ across the groups; however, participants in the medication contingency group achieved significantly more weeks of continuous abstinence from opiates and cocaine compared with participants in the voucher group (Ms = 5.95 and 2.90, respectively). Results suggest that the use of medication-based contingencies in combination with behavioral therapy in promoting drug abstinence may have clinical utility. Limitations of the study are discussed.

Adult↗

Characterizing nicotine withdrawal in pregnant cigarette smokers.

Maternal smoking is a leading preventable cause of poor pregnancy outcomes and infant morbidity and mortality. Whereas pregnancy has been thought of as a "window of opportunity" when women are more motivated to change health behaviors such as smoking, only 20% of pregnant women quit smoking upon learning they are pregnant and remain abstinent at the end of the pregnancy. Greater understanding of possible obstacles to smoking during pregnancy, such as nicotine withdrawal, is needed. The symptoms of nicotine withdrawal have been well characterized in nonpregnant smokers, but there has been only 1 report conducted during pregnancy, and that was a retrospective study. The aim of the present study was to characterize nicotine withdrawal and craving in pregnant cigarette smokers. These data were collected as part of prospective clinical trials assessing the efficacy of voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum. The authors examined results from the Minnesota Nicotine Withdrawal Scale (J. R. Hughes & D. K. Hatsukami, 1998) in 27 abstainers (reported no or very low levels of smoking, which was confirmed biochemically) and 21 smokers (smoked at >80% of their baseline smoking level) during the first 5 days of a cessation attempt. Abstainers reported more impatience, anger, and difficulty concentrating than did smokers. The results also suggest that pregnant smokers generally may have elevated baseline levels of withdrawal, which need to be considered in the design and analysis of future studies.

Adult↗

A meta-analysis of voucher-based reinforcement therapy for substance use disorders.

AIMS: To systematically investigate the effectiveness of voucher-based reinforcement therapy for the treatment of substance use disorders. METHODS: Effect sizes and 95% confidence intervals were calculated for studies published between January 1991 and March 2004 that utilized voucher-based reinforcement therapy (VBRT) or related monetary-based incentives to treat substance use disorders (SUDs). FINDINGS: Thirty studies involved interventions targeting abstinence from drug use using experimental designs where effects on treatment outcome could be attributed to the VBRT intervention. The estimated average effect size (r) for those studies was 0.32 (95% CI 0.26-0.38). Analyses of variables thought to moderate VBRT effect sizes revealed that more immediate voucher delivery and greater monetary value of the voucher were associated with larger effect sizes. Additional studies were identified wherein VBRT was used to target clinic attendance (n = 6) or medication compliance (n = 4). VBRT studies targeting attendance produced average effect sizes of 0.15 (95% CI 0.02-0.28), while those that targeted medication compliance produced an average effect of 0.32 (95% CI 0.15-0.47). No significant moderators were identified for these 10 studies. CONCLUSIONS: Overall, VBRT generated significantly better outcomes than did control treatments. These results further support the efficacy of VBRT, quantify the magnitude of its effects, identify significant moderators and suggest potential directions for future research.

Humans↗

Stress and alcohol consumption in heavily drinking men: 2 years of daily data using interactive voice response.

BACKGROUND: The relationship between stress and alcohol consumption has been shown in recent research to be more complex than originally thought. Cross-sectional and short-term longitudinal studies may not provide adequate data to address subtle but important relationships that impact consumption frequency and/or quantity. METHODS: Participants were 33 males recruited from local bars who reported their alcohol consumption, stress, and other related variables every day for 2 years. Reports were provided by automated telephone to a computer-based interactive voice response (IVR) system. By closely monitoring call completion, we were able to collect over 95% of the daily calls. RESULTS: Using hierarchical linear modeling, daily stress was found to be associated with daily alcohol consumption, but in the opposite direction than would be predicted by a "drinking to cope" hypothesis. That is, same-day stress was found to be inversely related to consumption levels. Prior day's stress was not significantly associated with subsequent day's consumption; however, prior day's consumption was predictive of subsequent stress for up to 2 days. Similar analyses using week, rather than day, as the unit of measure paralleled these findings. CONCLUSIONS: This study highlights the utility of using long-term daily process data to address important research and clinical questions in the alcohol field.

Alcohol Drinking↗

Influence of the duration of abstinence on the relative reinforcing effects of cigarette smoking.

RATIONALE: Sustaining smoking abstinence during the initial weeks of a cessation effort is highly correlated with long-term smoking abstinence. However, experimental research is needed to establish a direct causal relationship between achieving early abstinence and lowered relapse risk. OBJECTIVE: In the present study, we tested whether a period of sustained abstinence directly decreases the relative reinforcing effects of cigarette smoking. METHODS: Participants were 63 adult smokers who were randomized into one of three conditions: 14-day (14C), 7-day (7C), and 1-day (1C) contingent payment for smoking abstinence. Smoking status was assessed three times per day for 14 consecutive days using breath carbon monoxide monitoring and an abstinence criterion of < or = 4 ppm. In the 14C condition, monetary payment was contingent on abstinence for all 14 days; in the 7C condition, payment was noncontingent for days 1-7 and contingent for days 8-14; in the 1C condition, payment was noncontingent for days 1-13 and contingent for day 14. On day 14, all participants completed a 3-h preference session under controlled laboratory conditions wherein they could make a maximum of 20 exclusive choices between options to smoke (two puffs/choice) or earn money (0.25 dollars/choice). Preference was deemed an index of the relative reinforcing effects of smoking and money. RESULTS: A significantly lower proportion of participants in the 14C condition ever chose the smoking option (19%) compared to those in the 7C (57%) or 1C (62%) conditions. CONCLUSIONS: These results provide experimental evidence that sustained abstinence can decrease the relative reinforcing effects of smoking, an effect that may be related to the commonly observed decrease in relapse risk among those who are able to sustain smoking abstinence during the initial weeks of a cessation effort.

Adult↗

Electrical impedance along connective tissue planes associated with acupuncture meridians.

BACKGROUND: Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone) visible by ultrasound have greater electrical conductance (less electrical impedance) than non-meridian, parallel control segments. METHODS: We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC) constant amplitude current was introduced at three different amplitudes (20, 40, and 80 microAmps) to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity). RESULTS: At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 +/- 5.7 Omega) compared with control segments (75.0 +/- 5.9 Omega) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 +/- 6.8 Omega) and control segments (68.5 +/- 7.5 Omega) were not significantly different (p = 0.70). CONCLUSION: Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue.

Adult↗

Buprenorphine treatment for opioid dependence: the relative efficacy of daily, twice and thrice weekly dosing.

This randomized clinical trial evaluated the relative efficacy of three buprenorphine dosing schedules. Opioid-dependent adults were randomly assigned to receive buprenorphine seven, 3 or 2 days per week for 24 weeks. Daily maintenance doses were 4, 8, 10, or 12 mg of the sublingual buprenorphine solution. Participants who attended the clinic daily received a maintenance dose of buprenorphine daily. Participants who attended the clinic thrice weekly received double their maintenance dose on Monday and Wednesday, followed by a triple dose on Friday. Participants who attended the clinic twice weekly received quadruple their maintenance dose of buprenorphine on Monday and triple their maintenance dose on Friday. Results demonstrated that all dosing regimens were of comparable efficacy in promoting treatment retention, opioid and cocaine abstinence, and reductions in HIV risk behavior (especially as related to drug use) and severity of life problems. Predictor analyses identified sub-populations of opioid-dependent individuals that may have a more positive treatment outcome under each buprenorphine dosing condition. Less-than-daily dosing schedules may provide the opportunity for treatment programs to serve a greater number of opioid-dependent patients and reduce the risk of medication diversion, which may, in turn, have a positive impact on community support of science-based treatment for opioid-dependence.

Adult↗

Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial.

CONTEXT: The prevalence of heroin and other opioid use has markedly increased among adolescents in the last decade; however, virtually no research has been conducted to identify effective treatments for this population. OBJECTIVE: To evaluate the relative efficacy of 2 pharmacotherapies, the partial opioid agonist buprenorphine hydrochloride and the centrally active alpha(2)-adrenergic blocker clonidine hydrochloride, in the detoxification of opioid-dependent adolescents. DESIGN, SETTING, AND PATIENTS: A double-blind, double-dummy, parallel-groups randomized controlled trial conducted in a university-based research clinic from October 2001 to December 2003. Patients were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid dependence (ages 13-18 years eligible). INTERVENTIONS: Participants were randomly assigned to a 28-day, outpatient, medication-assisted withdrawal treatment with either buprenorphine or clonidine. Both medications were provided along with thrice weekly behavioral counseling and incentives contingent on opiate abstinence. Postdetoxification, all participants were offered the opportunity for continued treatment with the opiate antagonist, naltrexone hydrochloride. MAIN OUTCOME MEASURES: Treatment retention, opiate abstinence, and human immunodeficiency virus risk behavior, along with measures of withdrawal and medication effects. RESULTS: A significantly greater percentage of adolescents who received buprenorphine were retained in treatment (72%) relative to those who received clonidine (39%) (P<.05). For those in the buprenorphine group, a significantly higher percentage of scheduled urine test results were opiate negative (64% vs 32%; P = .01). Participants in both groups reported relief of withdrawal symptoms and drug-related human immunodeficiency virus risk behavior. Those in the buprenorphine condition generally reported more positive effects of the medication. No evidence of opioid intoxication or psychomotor impairment was observed. Sixty-one percent of participants in the buprenorphine condition and 5% of those in the clonidine group initiated treatment with naltrexone. CONCLUSION: Combining buprenorphine with behavioral interventions is significantly more efficacious in the treatment of opioid-dependent adolescents relative to combining clonidine and behavioral interventions.

Administration, Cutaneous↗

The influence of pregnancy on arterial compliance.

OBJECTIVE: To examine the effect of pregnancy and the interval between pregnancies on arterial compliance as measured by mean arterial pressure (MAP) and pulse pressure. METHODS: We conducted a 3-month chart review of deliveries at a tertiary care hospital (index pregnancies). Data collected included demographics, obstetric history, blood pressures, prepregnancy weight, weight gain, and neonatal outcome. If a subject's first delivery occurred at our institution, these records were reviewed in a similar fashion. Mean antepartum MAP and pulse pressure were calculated and compared for each trimester between index and first pregnancies. Statistical methods employed included repeated measures analysis of variance, repeated measures analysis of covariance, and correlation analysis. RESULTS: Two hundred eighty-five charts were reviewed. Forty-seven women had complete data covering both index and first pregnancy. Mean arterial pressure was significantly higher in all trimesters of first compared with index pregnancies (first pregnancy-first trimester 82.0 +/- 8.1 mm Hg, index pregnancy-first trimester 79.4 +/- 7.6 mm Hg, P = .032; first-second trimester 81.6 +/- 6.7 mm Hg, index-second trimester 78.7 +/- 6.6 mm Hg, P = .016; first-third trimester 83.9 +/- 6.9 mm Hg, index-third trimester 81.6 +/- 6.9 mm Hg, P = .047). Repeated measures analysis of covariance confirmed that pregnancy order contributed independently to differences in MAP. The interval between pregnancies was found to be inversely related to the difference in MAP from first to index pregnancies by trimester (r = -0.41, P = .004) and the change in MAP within pregnancy from first to third trimester (r = -0.31, P = .046). CONCLUSION: Mean arterial pressure is reduced in subsequent pregnancies compared with first pregnancies. This raises the possibility that pregnancy plays a role in modifying cardiovascular compliance. Consistent with this, the effect has temporal limitations in that the shorter the interval between pregnancies, the greater the reduction in MAP.

Adult↗

Maternal smoking and its association with birth weight.

OBJECTIVE: Maternal smoking has been associated with a reduction in newborn birth weight. We sought to estimate how the pattern of maternal smoking throughout pregnancy influences newborn size. METHODS: One hundred sixty pregnant smoking women were enrolled in a prospective study. We collected data on maternal age, education, prepregnancy body mass index, and parity, as well as alcohol and illicit drug use. Cigarette use was defined as self-reported consumption before pregnancy, at the time of study enrollment, and in the third trimester. Statistical analyses were performed based on bivariate correlations and multiple linear regression. RESULTS: Of the smoking parameters examined, maternal third-trimester cigarette consumption was the strongest predictor of birth weight percentile (partial r = -0.23, P < .001). For each additional cigarette per day that a participant smoked in the third trimester, there was an estimated 27 g reduction in birth weight. Prepregnancy smoking volume was not significantly associated with birth weight percentile in bivariate (r = -0.06, P = .47) or multivariable analyses. Additional factors contributing to birth weight include gestational age (partial r = 0.69, P < .001), maternal body mass index (partial r = 0.23, P < .001), and parity (partial r = 0.16, P < .004). In total, these 4 variables explain 61% of the variance in newborn birth weight. CONCLUSION: Maternal third-trimester cigarette consumption is a strong and independent predictor of birth weight percentile. This supports the hypothesis that reductions in maternal cigarette consumption during pregnancy will result in improved birth weight, regardless of the prepregnancy consumption levels. LEVEL OF EVIDENCE: III.

Adult↗

Exploring drinking dynamics using interactive voice response technology.

OBJECTIVE: Neurocognitive models of alcohol use and mathematical models of drinking patterns suggest that levels of drinking on one day should affect probabilities of drinking on subsequent days. However, there has been no demonstration in the alcohol literature that these structured temporal dependencies appear in daily patterns of alcohol use. A model of daily drinking is presented that relates probabilities of drinking on any day to amounts consumed 1 day and 1 week before. It is assumed that positive and negative experiences with alcohol shape drinking levels and probabilities of subsequent drinking. The model predicts that nonmonotonic functions will relate drinking levels to subsequent drinking probabilities. Maxima of these functions represent optimal drinking levels that provide greatest positive returns from any drinking occasion for each drinker. METHOD: Interactive Voice Response technology was used to obtain annual time series of daily drinking levels from 33 drinkers sampled from public establishments in Vermont. Two predictions from the model were tested: (1) Temporal dependencies exist between the onset of drinking events over time; and (2) these dependencies are nonmonotonically related to prior drinking levels. Dynamics were separately assessed for each drinker using bootstrapped logistic regression models. RESULTS: Thirty respondents provided data suitable for analysis. Time series data from five of these respondents exhibited no temporal dynamics (17%). Data from 25 respondents exhibited either daily or weekly dynamics (83%). Data from 18 respondents exhibited the expected nonmonotonic relationship between drinking levels and subsequent drinking events (60%). CONCLUSIONS: Daily probabilities of drinking were conditional upon and nonmonotonically related to prior drinking levels among a majority of respondents. The results of the study support models of daily drinking in which positive and negative experiences with alcohol shape daily drinking patterns.

Adult↗

Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo.

Cytoskeleton-dependent changes in cell shape are well-established factors regulating a wide range of cellular functions including signal transduction, gene expression, and matrix adhesion. Although the importance of mechanical forces on cell shape and function is well established in cultured cells, very little is known about these effects in whole tissues or in vivo. In this study we used ex vivo and in vivo models to investigate the effect of tissue stretch on mouse subcutaneous tissue fibroblast morphology. Tissue stretch ex vivo (average 25% tissue elongation from 10 min to 2 h) caused a significant time-dependent increase in fibroblast cell body perimeter and cross-sectional area (ANOVA, P < 0.01). At 2 h, mean fibroblast cell body cross-sectional area was 201% greater in stretched than in unstretched tissue. Fibroblasts in stretched tissue had larger, "sheetlike" cell bodies with shorter processes. In contrast, fibroblasts in unstretched tissue had a "dendritic" morphology with smaller, more globular cell bodies and longer processes. Tissue stretch in vivo for 30 min had effects that paralleled those ex vivo. Stretch-induced cell body expansion ex vivo was inhibited by colchicine and cytochalasin D. The dynamic, cytoskeleton-dependent responses of fibroblasts to changes in tissue length demonstrated in this study have important implications for our understanding of normal movement and posture, as well as therapies using mechanical stimulation of connective tissue including physical therapy, massage, and acupuncture.

Actins↗

Tissue displacements during acupuncture using ultrasound elastography techniques.

Acupuncture needle manipulation has been previously shown to result in measurable changes in connective tissue architecture in animal experiments. In this study, we used a novel in vivo ultrasound (US)-based technique to quantify tissue displacement during acupuncture manipulation in humans. B-scan ultrasonic imaging was performed on the thighs of 12 human subjects at different stages of needle motion, including varying amounts of rotation, downward and upward movement performed with a computer-controlled acupuncture needling instrument. Tissue displacements, estimated using cross-correlation techniques, provided successful mapping and quantitative analysis of spatial and temporal tissue behavior during acupuncture needle manipulation. Increasing amounts of rotation had a significant linear effect on tissue displacement during downward and upward needle motion, as well as on rebound tissue displacement after downward needle movement. In addition to being a valuable tool for studies of acupuncture's mechanism of action, this technique may have applications to other types of needling including biopsies.

Acupuncture Therapy↗

Examining interrelationships between abstinence and coping self-efficacy in cocaine-dependent outpatients.

Initial abstinence and self-efficacy predict treatment outcome in cocaine-dependent outpatients. Associations between abstinence and coping self-efficacy were examined among cocaine-dependent outpatients (N=126). Abstinence was verified by urinalysis. Coping self-efficacy was measured using a modified Situational Confidence Questionnaire (SCQ). The modified SCQ had good validity and reliability, and scores increased during treatment. In bivariate analyses, early abstinence and SCQ scores each predicted subsequent abstinence and confidence during treatment and posttreatment follow-up. Based on structural equation modeling, early confidence was a significant predictor of later confidence but not of later abstinence, whereas early abstinence was a significant predictor of later abstinence and confidence. Results suggest a unidirectional relationship wherein prior abstinence predicts subsequent abstinence and confidence.

Adult↗

An experimental examination of the initial weeks of abstinence in cigarette smokers.

Gaining experimental control over abstinence may help define processes that change during abstinence that may be related to the association between initial abstinence and relapse risk often noted in clinical trials. Adult smokers (n = 34) were randomly assigned to receive monetary incentives contingent on abstinence (CO +/- 4 ppm) or noncontingent for 12 days. Carbon monoxide (CO) tests were conducted 3 times per day, saliva samples were collected on Days 5 and 12, and all other measures were collected 1 time per day. In the contingent group, 59% of participants abstained throughout the study versus 0% in the control condition. Abstinence was associated with increases in participant-rated ease of abstaining and confidence in abstinence; nicotine withdrawal severity and craving decreased over time. Results indicate that it is feasible to experimentally manipulate smoking abstinence and that doing so can enhance understanding of the relationship between early abstinence and relapse risk.

Adult↗

An experimental test of the influence of prior cigarette smoking abstinence on future abstinence.

Significant positive associations between early and later abstinence are often reported in clinical trials on smoking cessation, but those relationships do not permit causal inferences. The present study was conducted to examine experimentally whether prior smoking abstinence histories can directly facilitate later abstinence, using a contingency management procedure to manipulate prior abstinence. A total of 40 adult cigarette smokers who were not trying to quit were randomly assigned to one of two conditions: Contingent ALL (C-ALL), who earned monetary incentives contingent on smoking abstinence during three 5 day experimental periods; or Contingent LAST (C-LAST), who earned incentives independent of abstinence during the first two periods (i.e., noncontingent payments) and contingent on abstinence during the final period. The contingency management procedure was effective in establishing different abstinence histories in the two conditions during the first two periods. Comparison of abstinence levels between the C-ALL and C-LAST conditions during the third period showed significantly greater abstinence in the C-ALL condition, although nicotine withdrawal and other subject ratings generally did not differ significantly between the two conditions. These results provide experimental evidence that prior abstinence histories can directly influence subsequent efforts to abstain from smoking.

Adolescent↗