U Busto’s research while affiliated with Centre for Addiction and Mental Health and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (70)


Figure 1: Subjective reports at baseline, pre- and post-scan time points in abstinence (ABS) and smoking (NIC) condition: (a). Factor 2 score (Questionnaire of Smoking Urges, QSU). (b). Emotionality factor (Tobacco Craving Questionnaire, TCQ. (c). Expectancy factor (Tobacco Craving Questionnaire, TCQ). (d). Urge to Smoke (UTS). (e). Minnesota Nicotine Withdrawal Scale (MNWS). (f). State-trait anxiety inventory (STAI). Mean±S.E.M.; *condition effect, P<0.05; #pairwise Bonferroni-corrected comparison between the time points, P<0.05.Download Power Point slide (780 KB)
Table 1 Subject Characteristics (n ¼ 10)
Figure 2: 11C](+)PHNO BPND in abstinence (empty circles) and smoking condition (full circles) in selected ROIs (n=10, except for VP, n=9). Left y axis: SN, substantia nigra; AST, associative striatum; LST, limbic striatum; SMST, sensorimotor striatum; Right y axis: VP, ventral pallidum; *P<0.05.Download Power Point slide (432 KB)
Figure 3 T-statistical overlaid average T1 MRI showing clusters of significantly reduced [ 11 C]-þ-PHNO BP ND after smoking a cigarette. Greatest decreases in [ 11 C]-þ-PHNO BP ND cluster in the ventral part of the striatum and in the area that corresponds to the ventral pallidum (t max ¼ 10.3; p FEW-corrected ¼ 0.03, k ¼ 736; x ¼ À 28, y ¼ À 10, z ¼ À 4). For visualization purposes the image is threshold at a Po0.05 uncorrected.
Figure 4: Relationship between [11C](+)PHNO BPND change in limbic striatum (LST), rate of smoking (puff number) and urge to smoke to relieve the negative affect (QSU/Factor 2; see in text for details on calculation). Pearson correlation coefficients (uncorrected r) and partial correlations coefficients (corrected r, controlling for the order of visits) are presented; *P<0.05.Download Power Point slide (1,185 KB)
Elevation of Dopamine Induced by Cigarette Smoking: Novel Insights from a &lsqb;11C&rsqb;-(&plus;)-PHNO PET Study in Humans
  • Article
  • Full-text available

August 2013

·

136 Reads

·

59 Citations

Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology

·

·

Alan A Wilson

·

[...]

·

Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here we used PET and [(11)C]-(+)-PHNO ([(11)C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), to test the hypothesis that smoking increases DA release (decreases [(11)C]-(+)-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behaviour. Ten participants underwent [(11)C]-(+)-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [(11)C]-(+)-PHNO binding in D2 and D3-rich areas (-12.0% and -15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3 rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [(11)C]-(+)-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.Neuropsychopharmacology accepted article preview online, 19 August 2013. doi:10.1038/npp.2013.209.

Download

Figure 2. [ 11 C]-(+)-PHNO BP ND in brain regions of interest. [ 11 C]-(+)-PHNO BP ND in the associative striatum (AST), limbic striatum (LST), sensorimotor striatum (SMST), globus pallidus (GP) and substantia nigra (SN) in the neutral and smoking cue conditions. There were no overall significant differences between the cue conditions in [ 11 C]-(+)-PHNO BP ND in any of the apriori selected regions of interest. doi:10.1371/journal.pone.0060382.g002
Figure 3. High cravers versus low cravers area under the visual analog scale curve and percent change in [ 11 C]-(+)-PHNO BP ND in regions of interest. (a) Area under the Visual Analog Scale curve in high cravers and low cravers. (b) Percent change in [ 11 C]-(+)-PHNO BP ND in the associative striatum (AST), limbic striatum (LST), sensorimotor striatum (SMST), globus pallidus (GP) and substantia nigra (SN) in high cravers versus low cravers. There were no significant differences in percent change in [ 11 C]-(+)-PHNO BP ND in any of the aprior regions of interest when comparing high cravers to low cravers (multivariate analysis of variance (MANOVA) F (5,10) = 0.759, p = 0.731). doi:10.1371/journal.pone.0060382.g003
(a) Visual analog scale measurements of craving for a cigarette assessed every fifteen minutes during cue-presentation (Blocks 1–4) and every 15 minutes following the completion of the paradigm (Blocks 5–6). There was a main effect of cue type (Repeated Measures Analysis of Variance (RM-ANOVA, F(1,17) = 6.935, p<0.05) and time (RM-ANOVA, F(7,119) = 18.098, p<0.005) on craving for a cigarette. (b) Withdrawal symptoms as rated by the Minnesota Nicotine Withdrawal Scale at baseline (prior to cue presentation) and at the end of the scan. There was a main effect of time on withdrawal symptoms (RM-ANOVA, F(1,17) = 23.996, p<0.001) (c) Cigarette craving as measured by the Questionnaire of Smoking Urges Factor 1 (urge to smoke for pleasure effects of smoking) and Factor 2 (urge to smoke for relief of negative effect of withdrawal) at baseline and at the end of the scan. There was a main effect of time on the urge to smoke for pleasurable effects (RM-ANOVA, QSU Factor 1 F(1,17) = 53.866, p<0.001) and on the urge to smoke for relief of negative symptoms (RM-ANOVA, QSU Factor 2, F(1,17) = 27.591, p <0.001) (d) Cigarette craving measured by the Tobacco Craving Questionnaire factors 1 (Emotionality), 2 (Expectancy), 3 (Compulsivity) and 4 (Purposefulness) at baseline and at the end of the scan. There was a main effect of time on the urge to smoke for relief of negative withdrawal effects (RM-ANOVA, TCQ 1/emotionality F(1,17) = 11.907, p<0.005), urge to smoke for pleasurable effects (RM-ANOVA, TCQ 2/expectancy F(1,17) = 25.510, p<0.001) and intention to smoke (RM-ANOVA, TCQ 4/purposefulness F(1,17) = 14.336, p<0.005). * p<0.05, ** p<0.01, *** p<0.005
[11C]-(+)-PHNO BPND in the associative striatum (AST), limbic striatum (LST), sensorimotor striatum (SMST), globus pallidus (GP) and substantia nigra (SN) in the neutral and smoking cue conditions. There were no overall significant differences between the cue conditions in [11C]-(+)-PHNO BPND in any of the apriori selected regions of interest.
(a) Area under the Visual Analog Scale curve in high cravers and low cravers. (b) Percent change in [11C]-(+)-PHNO BPND in the associative striatum (AST), limbic striatum (LST), sensorimotor striatum (SMST), globus pallidus (GP) and substantia nigra (SN) in high cravers versus low cravers. There were no significant differences in percent change in [11C]-(+)-PHNO BPND in any of the aprior regions of interest when comparing high cravers to low cravers (multivariate analysis of variance (MANOVA) F(5,10) = 0.759, p = 0.731).
Presentation of Smoking-Associated Cues Does Not Elicit Dopamine Release after One-Hour Smoking Abstinence: A [11C]-(+)-PHNO PET Study

March 2013

·

1,184 Reads

·

12 Citations

The presentation of drug-associated cues has been shown to elicit craving and dopamine release in the striatum of drug-dependent individuals. Similarly, exposure to tobacco-associated cues induces craving and increases the propensity to relapse in tobacco- dependent smokers. However, whether exposure to tobacco-associated cues elicits dopamine release in the striatum of smokers remains to be investigated. We hypothesized that presentation of smoking-related cues compared to neutral cues would induce craving and elevation of intrasynaptic dopamine levels in subregions of the striatum and that the magnitude of dopamine release would be correlated with subjective levels of craving in briefly abstinent tobacco smokers. Eighteen participants underwent two [(11)C]-(+)-PHNO positron emission tomography (PET) scans after one-hour abstinence period: one during presentation of smoking-associated images and one during presentation of neutral images. Smoking cues significantly increased craving compared to neutral cues on one, but not all, craving measures; however, this increase in craving was not associated with overall significant differences in [(11)C]-(+)-PHNO binding potential (BPND) (an indirect measure of dopamine release) between the two experimental conditions in any of the brain regions of interest sampled. Our findings suggest that presentation of smoking cues does not elicit detectable (by PET) overall increases in dopamine in humans after one-hour nicotine abstinence. Future research should consider studying smoking cue-induced dopamine release at a longer abstinence period, since recent findings suggest the ability of smoking-related cues to induce craving is associated with a longer duration of smoking abstinence.





Fig. 1. Areas of activation where cue reactivity during each scan session and between the pre-and post-smoking scans was significantly correlated with depression severity (HAMD). Activations in orange represent where cue reactivity was positively correlated whereas areas in blue represent negative correlations. During the pre-smoking scan HAMD was positively correlated with cue reactivity in inferior frontal gyrus (IFG), medial occipital lobe (MOL), middle frontal gyrus (MFG), hippocampus (HC), middle cingulate cortex (MCC), superior frontal gyrus (SFG), and anterior cingulate gyrus (ACG) ; and negatively correlated in supplementary motor area (SMA). During the post-smoking scan HAMD was positively correlated with cue reactivity in the MFG, superior temporal gyrus (STG), and superior occipital cortex (SOC) ; and negatively correlated in the superior parietal lobule (SPL), SFG, postcentral gyrus (PostCG), precentral gyrus (PreCG), lingual gyrus (LG), and temporal pole (TP). Differential cue reactivity between the pre-smoking and post-smoking scans was positively correlated with HAMD in the STG, PostCG, PreCG, hippocampus (HC), insula (INS), superior temporal lobe (STL), and fusiform gyrus (FG) ; and negatively correlated in the middle temporal gyrus (MTG). Numbers in the top left corner of each brain slice represent the z coordinate in MNI space. pf0.005 (uncorrected), minimum cluster size o10 voxels. 
Table 1 . Brain areas where neural reactivity to smoking cues vs. neutral cues as measured by BOLD signal during the pre-smoking scan was significantly correlated with HAMD scores 
Table 2 . Brain areas where neural reactivity to smoking cues vs. neutral cues as measured by BOLD signal during the post-smoking scan was significantly correlated with HAMD scores 
Brain areas where neural reactivity to smoking cues vs. neutral cues between pre-smoking and post-smoking scans was significantly correlated with HAMD scores 
Enhanced smoking cue salience associated with depression severity in nicotine-dependent individuals: A preliminary fMRI study

July 2010

·

90 Reads

·

33 Citations

The International Journal of Neuropsychopharmacology

The association between cigarette smoking and depression has been well documented; however, little research has been done to elucidate the neurobiological substrates of this highly prevalent comorbidity. We used multiple linear regression analysis to evaluate the relationship between depression severity as assessed by the Hamilton Depression Rating Scale (HAMD) and blood oxygen level-dependent (BOLD) responses to visual smoking cues in drug-free nicotine-dependent smokers (n=18). Two functional magnetic resonance imaging (fMRI) scans were completed over a single study day, following overnight smoking abstinence (pre-smoking scan) and after cigarette reinstatement (post-smoking scan). During the pre-smoking scan positive correlations between BOLD activity and HAMD scores were observed in areas of the mesocorticolimbic dopaminergic system [inferior frontal gyrus, middle frontal gyrus (MFG), hippocampus (HC), anterior cingulate gyrus] and areas of the visuospatial attention circuit (medial occipital lobe, middle cingulate cortex, superior frontal gyrus, angular gyrus). During the post-smoking scan positive correlations were observed in areas of the brain implicated in drug expectancy (MFG), memory (HC), attentional motivation (posterior cingulate cortex), and visual processing and attention (precuneus). These preliminary findings demonstrate that smokers with higher depression severity attribute greater incentive salience to smoking-related cues and this is especially pronounced during periods of acute abstinence. Such enhanced salience of smoking cues, even after smoking a cigarette, may play a critical role both in the maintenance of smoking in depression and in greater levels of nicotine dependence seen in this patient population.


Pediatric Cancer Rates After Universal Folic Acid Flour Fortification In Ontario

May 2010

·

42 Reads

·

45 Citations

Following the introduction of mandatory Canadian folic acid flour fortification in mid-1997, the incidence of selected childhood cancers that declined in Ontario prior to and subsequent to this public policy initiative was examined. A population-based cohort study of all incident cases of childhood malignancy in Ontario between the years 1985 and 2006 was conducted. Participants were identified from a database provided by the Pediatric Oncology Group of Ontario and included children 0 to 4 years of age and 5 to 9 years of age who were diagnosed with cancer. Among children aged 0 to 4 years, the incidence rate of Wilms' tumor declined from 1.94 to 1.43 per 100,000 (incidence rate ratio 0.74, 95% confidence interval, 0.57-0.95). No significant change was seen in the prefortification vs postfortification time periods for acute lymphoblastic leukemia, brain cancers, or embryonal cancers among the 0- to 4-year or 5- to 9-year age groups. There was an approximately 30% reduction in risk of Wilms' tumor following introduction of the initiative. This corroborates a recent case-control study from Germany. These data may also provide some reassurance that universal flour fortification does not heighten the risk of pediatric cancer.


Effect of metabolic blockade on the psychoactive effects of dextromethorphan

January 2010

·

113 Reads

·

26 Citations

Human Psychopharmacology Clinical and Experimental

Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM. In a single-blind, within-subjects study, eight healthy volunteers (all homozygous for the wild type allele for CYP2D6) received placebo and varying doses of DM, both with and without quinidine pre-treatment. Pharmacokinetic and pharmacodynamic measures were assessed at baseline and every hour post-drug for 6 h. Compared to the no quinidine condition, quinidine pre-treatment decreased the area under the dose-response curve on subjective measures of positively reinforcing effects (e.g., euphoria, p < 0.04; drug liking, p < 0.05), and was significantly greater for measures of dysphoria (e.g., unpleasantness, p < 0.02). These changes corresponded to increased DM and decreased dextrorphan plasma concentrations. Compared to DM alone, quinidine pre-treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM.


The impact of chronic bupropion on plasma cotinine and on the subjective effects of ad lib smoking: A randomized controlled trial in unmotivated smokers

September 2009

·

33 Reads

·

16 Citations

Addictive Behaviors

Bupropion is an efficacious non-nicotine medication for smoking cessation; however, its cessation-mediating mechanism is unclear. This randomized, placebo-controlled trial examined the effect of bupropion SR (300 mg/day for 6 weeks) on plasma cotinine and on the subjective effects of smoking in 24 current daily smokers who were not trying to quit or reduce smoking. Subjective effects of smoking, as well as cue-elicited responses were assessed at bi-weekly experimental sessions using validated scales. Several indices of cigarette consumption were measured. Plasma cotinine decreased from 280 (+/-133) microg/l at baseline to 205 (+/-108) microg/l at end of treatment in the bupropion group (p=0.036), but no significant change was found in the placebo group. Daily cigarette count and puff topography did not significantly change in either group. In contrast to placebo, bupropion increased post-smoking satiety (p=0.045). Both groups reported higher craving (p=0.025) and withdrawal (p=0.014) after exposure to smoking-related pictures, compared to neutral pictures. This biased reactivity was not significantly affected by treatment condition (p>0.1). Therefore, bupropion does not appear to impact the smokers' response to conditioned smoking-related cues but influences the unconditioned subjective effects of smoking in unmotivated smokers. This study is among the first to systematically investigate the effect of chronic bupropion administration, free from the confounding effect of the smoker's motivation to quit smoking.


Objective Determination of Benzodiazepine Use and Abuse in Alcoholics

January 2006

·

19 Reads

·

13 Citations

Addiction

The extent of concurrent use and abuse of benzodiazepines and alcohol in chronic alcoholics is not known. Prospective data collected on 216 consecutive outpatient referrals between 1 June and 31 July 1981 (age range, 16 to 70 years, 75 per cent men) showed that benzodiazepines were detected in the urine of 33 per cent of patients undergoing medical assessment. Other drugs identified in urine were ethanol (5.0 %), codeine (1.99 %) and barbiturates (1.5 %). According to patient histories, the predictive value of benzodiazepine allegation was high for positive and negative allegation (0.87 and 0.83, respectively), indicating that patients reliably report benzodiazepine use if questioned. However, only one patient considered himself to be a benzodiazepine abuser. The proportion of women with a positive test for benzodiazepines (48%) was significantly higher than that of men (28%: X – 7.7; p <0.005). Among patients alleging use of benzodiazepines (n = 61), 54 per cent obtained the drug directly by prescription while 46 per cent obtained it indirectly (e.g. a relative, illicit source). Benzodiazepines were taken most frequently for anxiety (53%) and occasionally for alcohol withdrawal (10%). Forty-seven (54%) of the patients could be considered abusers of benzodiazepines (i.e. indirect source and/or cumulative drug exposure of >2700 mg of diazepam or equivalent and a positive urine test). These results · indicate that benzodiazepines are very commonly used and abused by alcoholics. Treatment programmes for alcoholics should identify such patients, consider directing treatment toward control of benzodiazepine use, and monitor changes in benzodiazepine use during and after treatment.


Citations (40)


... The withdrawal symptoms include anxiety, agitation, irritability, hallucinations, insomnia, anorexia, seizures, and coma. The rate and severity of withdrawal symptoms depend on several factors such as the duration of therapy, daily dosage, the elimination half-life, and the potency of a BZD, and the tapering rate [212,213]. ...

Reference:

Black-Box Warnings of Antiseizure Medications: What is Inside the Box?
Withdrawal reaction after long-term therapeutic use of benzodiazepines
  • Citing Article
  • February 1987

Journal of Clinical Psychopharmacology

... Psychotropic drugs comprise one of the most commonly prescribed categories of drugs in industrialised countries. Over the past twenty years, the widespread use of these types of drugs and specifically the potential for abuse and dependency of benzodiazepines have become an area of concern for scholars in a variety of fields (Cappell et al 1986). In assessing the issue of psychotropics on an international scale, medical experts have suggested that if the character of psychotropic drug use is to be understood and indeed effective health and social policies are to be developed, the abuse potential and dependency liability of these drugs be thoroughly investigated (Idanpaa-Heikkila et al 1987, Medawar 1992. ...

Benzodiazepines as Drugs of Abuse and Dependence
  • Citing Chapter
  • January 1986

... Because 88% of benzodiazepine users report the additional consumption of alcohol and 28% indicate intentional combined use (Ilomäki et al., 2013), it is important to clarify the potential impact of their combination for road safety. Past reviews in this area have taken a broader approach to investigating the pharmacodynamic interaction between alcohol and benzodiazepines (Moody, 2012;Sellers & Busto, 1982). Thus, rather than reiterate these conclusions, this review aims to provide an updated and concise synthesis of the available experimental research that has examined the effect of the combination of alcohol and benzodiazepines on neurocognitive domains implicated in driving performance. ...

Benzodiazepines and Ethanol
  • Citing Article
  • August 1982

Journal of Clinical Psychopharmacology

... This clinical case report shows mirtazapine-induced hyponatremia in a patient with systemic mastocytosis. Using the Naranjo ADR Probability Scale, the score was 9, which indicates hyponatremia caused by the newly introduced drugmirtazapine (Naranjo et al. 1981). ...

Empiric delineation of the probability spectrum of adverse drug reactions
  • Citing Article
  • January 1981

Clinical Pharmacology & Therapeutics

... After smoking, subjects had significantly decreased withdrawal symptoms and cravings, and motivation to smoke corresponded with the amount of dopamine released in the striatum. D3 areas had increased dopamine release after smoking compared to other areas, indicating a possible role for D3 receptors in cravings and withdrawal symptoms [61]. ...

Elevation of Dopamine Induced by Cigarette Smoking: Novel Insights from a &lsqb;11C&rsqb;-(&plus;)-PHNO PET Study in Humans

Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology

... The potent dopamine D 2 /D 3 receptor agonist (+)-PHNO ((+)-4-propyl-3,4,4a,5,6,10bhexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol, molecular weight 247.33 g/mol) can cause nausea, vomiting and orthostatic hypotension, at doses of 0.25 mg three times a day (Weiner et al. 1989). In initial clinical studies using the radiotracer (+)-[ 11 C]PHNO, participants commonly experienced nausea (Willeit et al. 2006(Willeit et al. , 2008Chiuccariello et al. 2013). Houle and co-workers subsequently recommended a dose below 0.029 µg/kg for (+)-[ 11 C]PHNO, and therefore a maximum administered dose of 2.03 µg for a 70 kg participant, which is even lower than for [ 11 C]carfentanil (Blecha et al. 2017). ...

Presentation of Smoking-Associated Cues Does Not Elicit Dopamine Release after One-Hour Smoking Abstinence: A [11C]-(+)-PHNO PET Study

... The GDS is a 30-item questionnaire used to screen for depression among elderly people. 9 The cutoff scores and their interpretation are as follows: 0-9: No depression present 10-19: Mild depression likely 20-30: Severe depression likely. ...

A validation study of the Geriatric Depression Scale (GDS) short form
  • Citing Article
  • May 1996

International Journal of Geriatric Psychiatry

... In addition, HI can cause a variety of pathophysiologic conditions such as renal dysfunction [4,5] or gastrointestinal bleeding [6]. Accordingly, HI has been identified as a risk factor for drug safety, leading to adverse drug reactions (ADR) [7][8][9]. To prevent ADR, drug therapy needs to be reviewed in terms of drug choice and dose adjustment. ...

Adverse drug reactions in liver cirrhosis
  • Citing Article
  • November 1978

European Journal of Clinical Pharmacology

... A growing body of neuroimaging research has been examining the neural correlates of cigarette smoking as well as externalizing and internalizing behaviors. The insula and anterior cingulate cortex (ACC), two key nodes of the salience network, have been implicated in cigarette smoking and craving [19][20][21]. Positively correlated with individual variation in nicotine addiction severity, insula and ACC responses to smoking vs. neutral cues distinguished smokers who relapsed from those who maintained abstinence [22]. In addition, greater insula reactivity to negative emotional stimuli was associated with more severe smoking [23]. ...

Enhanced smoking cue salience associated with depression severity in nicotine-dependent individuals: A preliminary fMRI study

The International Journal of Neuropsychopharmacology

... American and Canadian ecologic studies have demonstrated a decline in childhood cancer incidence after folic acid fortification was initiated, with an estimated dose below 0.4 mg per day. [152][153][154] Other papers have indicated a minimized risk of childhood central nervous system tumors 155 and ALL 25,156,157 according to self-reported folic acid consumption at doses nearly 0.4 mg per day, with no certain consumption of more than 0.8 mg. There was no detected change in the prefortification versus post fortification duration for ALL, brain cancers, embryonal cancers, or hepatoblastoma among the 0-to 4-year or 5-to 9-year age groups. ...

Pediatric Cancer Rates After Universal Folic Acid Flour Fortification In Ontario
  • Citing Article
  • May 2010