Prevalence and Correlates of Cannabis Use in Massachusetts after Cannabis Legalization and before Retail Sales.

We determined the prevalence and correlates of cannabis use in Massachusetts after recreational use was passed, but before recreational cannabis stores opened. A cross-sectional, population-based survey of Massachusetts adults, age 18 years or older, (n = 3,022) was conducted in November-December, 2017. We estimated population-level prevalence and correlates of past 30-day cannabis use. 21.1% [95% CI: 18.6, 23.6] of Massachusetts adults reported past 30-day cannabis use. Among cannabis users, 56.0% [CI 49.1, 62.9] reported non-medical cannabis use, 15.5% [12.1, 18.9] reported medical cannabis use, and 28.5% [CI 22.3, 34.8] reported both types of use. Men were more likely than women to use cannabis (Risk Ratio: 1.3 [CI 1.1, 1.6]), as were young adults (18-25 years old), those with lower socioeconomic status, non-parenting individuals, those who used alcohol (1.9 [CI 1.4, 2.6]) or other substances (1.7 [CI 1.3, 2.4]), and residents of Western Massachusetts (2.0 [1.3, 3.0]; ref: Boston area), the Northeast (1.8 [CI 1.2, 2.7]), and the Southeast (1.8 [CI 1.1, 2.7]). Cannabis is widely used in Massachusetts, with varying prevalence rates by gender, age, socioeconomic status, poly-substance use, and region. Findings may inform public health efforts and serve as a baseline for measuring health and social impacts of opening retail cannabis stores.

Estimating the range of the maximum hormetic stimulatory response.

An ever-expanding hormetic database (HDB) was used to demonstrate that the median maximal hormetic stimulatory response (MHSR) of biphasic dose-response relationships increases in value with an increase in the number of stimulatory doses/concentrations that are administered below the estimated threshold/ZEP (zero equivalent point - i.e., the dose where the response crosses the control group value). With only one dose or concentration administered below the ZEP, the median MHSR for microbes (in vitro), animals (in vitro and in vivo), and plants (in vitro and in vivo) ranged between 120% and 125% of the control response. However, when individual agents having at least six doses below the ZEP were mined from the HDB (and a median MHSR then determined), the median MHSR increased to 160-190%. This progressive increase in the MHSR appears to be due to several factors, including (i) the enhanced capacity of additional doses in the stimulatory hormetic zone to better estimate the response optima, and (ii) enhanced variability due to the presence of more doses in the stimulatory zone. This study offers a novel perspective for improving research protocols, unraveling the limits of biological plasticity, understanding low-level stress biology, advancing human and ecological health, and enhancing human performance.

The importance of friends and family to recreational gambling, at-risk gambling, and problem gambling.

BACKGROUND: The variables correlated with problem gambling are routinely assessed and fairly well established. However, problem gamblers were all 'at-risk' and 'recreational' gamblers at some point. Thus, it is instructive from a prevention perspective to also understand the variables which discriminate between recreational gambling and at-risk gambling and whether they are similar or different to the ones correlated with problem gambling. This is the purpose of the present study. METHOD: Between September 2013 to May 2014, a representative sample of 9,523 Massachusetts adults was administered a comprehensive survey of their past year gambling behavior and problem gambling symptomatology. Based on responses to the Problem and Pathological Gambling Measure, respondents were categorized as Non-Gamblers (2,523), Recreational Gamblers (6,271), At-Risk Gamblers (600), or Problem/Pathological Gamblers (129). With the reference category of Recreational Gambler, a series of binary logistic regressions were conducted to identify the demographic, health, and gambling related variables that differentiated Recreational Gamblers from Non-Gamblers, At-Risk-Gamblers, and Problem/Pathological Gamblers. RESULTS: The strongest discriminator of being a Non-Gambler rather than a Recreational Gambler was having a lower portion of friends and family that were regular gamblers. Compared to Recreational Gamblers, At-Risk Gamblers were more likely to: gamble at casinos; play the instant and daily lottery; be male; gamble online; and be born outside the United States. Compared to Recreational Gamblers, Problem and Pathological Gamblers were more likely to: play the daily lottery; be Black; gamble at casinos; be male; gamble online; and play the instant lottery. Importantly, having a greater portion of friends and family who were regular gamblers was the second strongest correlate of being both an At-Risk Gambler and Problem/Pathological Gambler. CONCLUSIONS: These analyses offer an examination of the similarities and differences between gambling subtypes. An important finding throughout the analyses is that the gambling involvement of family and friends is strongly related to Recreational Gambling, At-Risk Gambling, and Problem/Pathological Gambling. This suggests that targeting the social networks of heavily involved Recreational Gamblers and At-Risk Gamblers (in addition to Problem/Pathological Gamblers) could be an important focus of efforts in problem gambling prevention.

The Health Behaviors of Ethnically Diverse Women at Increased Risk of Gestational Diabetes: The Behaviors Affecting Baby and You (B.A.B.Y.) Study.

Objectives Cigarette smoking, low physical activity, and sedentary behavior are modifiable risk factors for adverse pregnancy outcomes. However, only one study has evaluated predictors of these health risk behaviors among women at high risk for gestational diabetes mellitus (GDM). Therefore, our goal was to examine predictors of smoking, low physical activity, and sedentary behavior during pregnancy in an ethnically diverse high risk cohort. Methods This cross-sectional analysis utilized baseline data from the Behaviors Affecting Baby and You (B.A.B.Y.) study conducted among prenatal care patients at high risk for GDM (personal history of GDM or family history of diabetes and body mass index [BMI] ≥ 25 kg/m2). Smoking was assessed using questions from the Pregnancy Risk Assessment Monitoring System questionnaire and sedentary behavior (top vs. lower quartiles) and moderate/vigorous physical activity (bottom vs. upper quartile) via the Pregnancy Physical Activity Questionnaire. Results Participants (n = 400) enrolled at a mean of 12.4 (SD 3.6) weeks gestation. A total of 150 (44.1%) engaged in one, 37 (10.9%) in two, and 4 (1.2%) in three risk behaviors. Lower household income and not having children at home were each associated with a 2-6 fold increased odds of smoking, high sedentary behavior, and engaging in at least one risk behavior. Being married, Hispanic or of younger age was associated with a 2-6 fold reduced odds of smoking. BMI and personal history of GDM were not associated with risk behaviors. Conclusions for Practice Findings help characterize high risk groups and inform prenatal interventions targeting these health risk behaviors.

The Effect of an Exercise Intervention on Gestational Weight Gain: The Behaviors Affecting Baby and You (B.A.B.Y.) Study: A Randomized Controlled Trial.

PURPOSE: To examine the effect of a prenatal exercise intervention on gestational weight gain (GWG) and to update meta-analyses. DESIGN: Randomized controlled trial and meta-analysis. SETTING: Obstetrical practices in a Western Massachusetts hospital. PATIENTS: We analyzed 241 ethnically diverse pregnant participants at high risk for gestational diabetes in the Behaviors Affecting Baby and You (B.A.B.Y.) study. A total of 118 participants were randomized to an exercise intervention group and 123 to a comparison health and wellness intervention group. INTERVENTION: A 12-week individually tailored, motivationally matched program designed to increase the compliance with guidelines for exercise during pregnancy (30 min/day). MEASURES: The GWG and compliance with 2009 Institute of Medicine (IOM) guidelines for GWG abstracted from medical records. ANALYSIS: Unadjusted logistic regression, intent-to-treat. Results were added to the existing meta-analyses using a random effects model. RESULTS: Women randomized to the exercise group had a lower mean GWG than the comparison group (-0.97 kg, P value = .39) and were less likely to exceed IOM guidelines (odds ratio = 0.69, 95% confidence interval [CI] 0.34-1.40), but results were not statistically significant. Meta-analyses yielded a -0.63 kg (95% CI -1.17 to -0.08, P = .02) reduction in GWG and a 20% reduction in odds of exceeding IOM guidelines (95% CI 0.73 to 0.89) for the exercise intervention. CONCLUSION: Findings from this randomized trial among ethnically diverse women contribute to the results of meta-analyses supporting exercise as a means of attenuating GWG.

Intensive Language Action Therapy in Chronic Aphasia: A Randomized Clinical Trial Examining Guidance by Constraint.

Purpose: Intensive language action therapy (ILAT) can be effective in overcoming learned nonuse in chronic aphasia. It is suggested that all three guiding principles (constraint, communication embedding, massed practice) are essential to ILAT's success. We examined whether one of these, guidance by constraint, is critical. Method: Twenty-four participants with aphasia (PWAs) were assigned to ILAT or a modified version of promoting aphasic communicative effectiveness (PACE) in a randomized block, single-blind, parallel-group treatment study. Blocking was by severity (mild/moderate, moderate to severe, severe). Both groups received intensive treatment in the context of therapeutic language action games. Whereas the ILAT group was guided toward spoken responses, the PACE group could choose any response modality. Results: All participants, whether assigned to ILAT or PACE groups, improved on the primary outcome measure, picture naming. There was a Severity × Treatment interaction, with the largest effects estimated for PWAs with mild/moderate and moderate to severe aphasia. Regardless of severity, the ILAT group outperformed the PACE group on untrained pictures, suggesting some benefit of ILAT to generalization. However, this difference was not statistically significant. Conclusion: Although the groups differed in subtle ways, including better generalization to untrained pictures for ILAT, the study was inconclusive on the influence of guidance by constraint.

Urinary bisphenol-A, phthalate metabolites and body composition in US adults, NHANES 1999-2006.

BACKGROUND: Exposure to bisphenol-A (BPA) and phthalates is highly prevalent. Prior studies have not assessed associations between urinary levels of BPA and phthalate metabolites and body composition. METHODS: National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006 on adults aged ≥20 were analyzed by linear regression for associations between urinary BPA, monoethyl phthalate, monobutyl phthalate (MBP), monoethylhexyl phthalate (MEHP), and monobenzyl phthalate (MBzP) and lean mass, fat mass, and percent body fat. RESULTS: BPA and phthalate metabolites were not independently associated with fat mass or percent body fat. Significant inverse associations were observed with lean mass, with the strongest association observed for BPA in men (mean lean mass 1.39 kg lower for quartile 4 vs. quartile 1, p trend = 0.02). CONCLUSIONS: BPA and some phthalates could have important, negative effects on muscle and may affect conditions related to deficits in lean mass, though additional research is needed.

Effect of an exercise intervention on gestational diabetes mellitus: a randomized controlled trial.

OBJECTIVE: To examine the effect of an individually tailored, motivationally matched prenatal exercise intervention on gestational diabetes mellitus (GDM) and other measures of glucose intolerance among ethnically diverse prenatal care patients at increased risk for GDM. METHODS: The Behaviors Affecting Baby and You study randomized eligible women at a mean (standard deviation) of 18.2 (4.1) weeks of gestation to a 12-week individually tailored, motivationally matched exercise intervention or a comparison health and wellness intervention. The goal of the exercise intervention was to achieve the American College of Obstetricians and Gynecologists' guidelines for physical activity during pregnancy. Diagnosis of GDM, impaired glucose tolerance, abnormal glucose screen, and screening glucose values (mg/dL) were abstracted from medical records. A sample size of 352 women (176 per group) was planned to have 80% power to detect reductions in risk of 35% or larger. RESULTS: From July 2007 to December 2012, a total of 251 (86.5%) women completed the intervention; n=124 and 127 in the exercise and comparison interventions, respectively. Based on an intention-to-treat analysis, no statistically significant differences between the intervention groups were observed; the relative odds of GDM in the exercise group was 0.61 (95% confidence interval [CI] 0.28-1.32) as compared with the health and wellness comparison group. Odds ratios for impaired glucose tolerance and abnormal glucose screen were 0.68 (95% CI 0.35-1.34) and 0.86 (95% CI 0.51-1.47), respectively. The intervention had no effect on birth outcomes. CONCLUSION: In this randomized trial among ethnically diverse pregnant women at increased risk for GDM, we found that a prenatal exercise intervention implemented in the second trimester did not result in a statistically significant reduction in relative odds for GDM, impaired glucose tolerance, or abnormal glucose screen. LEVEL OF EVIDENCE: I.

Design-based random permutation models with auxiliary information¶

We extend the random permutation model to obtain the best linear unbiased estimator of a finite population mean accounting for auxiliary variables under simple random sampling without replacement (SRS) or stratified SRS. The proposed method provides a systematic design-based justification for well-known results involving common estimators derived under minimal assumptions that do not require specification of a functional relationship between the response and the auxiliary variables.

Prediction with measurement errors in finite populations.

We address the problem of selecting the best linear unbiased predictor (BLUP) of the latent value (e.g., serum glucose fasting level) of sample subjects with heteroskedastic measurement errors. Using a simple example, we compare the usual mixed model BLUP to a similar predictor based on a mixed model framed in a finite population (FPMM) setup with two sources of variability, the first of which corresponds to simple random sampling and the second, to heteroskedastic measurement errors. Under this last approach, we show that when measurement errors are subject-specific, the BLUP shrinkage constants are based on a pooled measurement error variance as opposed to the individual ones generally considered for the usual mixed model BLUP. In contrast, when the heteroskedastic measurement errors are measurement condition-specific, the FPMM BLUP involves different shrinkage constants. We also show that in this setup, when measurement errors are subject-specific, the usual mixed model predictor is biased but has a smaller mean squared error than the FPMM BLUP which point to some difficulties in the interpretation of such predictors.

Evidence for hormesis in mutagenicity dose-response relationships.

This study assessed the occurrence of hormetic dose responses from three previously published data sets [1-3] with 825 chemicals in three Ames assay tester strains (i.e., TA97, TA98, TA100) with and without the S9 fraction, using a five dose protocol and semi-log dose spacing. Ninety-five (95) (11.5%) chemicals satisfied the multiple a priori entry criteria, with a total of 107 assays. Of the assays satisfying the entry criteria, 61 involved TA100, a strain that detects base-pair substitution mutations. 29.5% (18/61) satisfied the statistical evaluative criteria for hormesis, exceeding that predicted by chance by 4.0-fold (p<0.001). The remaining 46 assays involved TA97 and TA98, strains that detect frameshift mutations. Of these 46 assays, the overall responses for the lowest two doses closely approximated the control response (e.g., 101.77% of the control for TA98; 99.20% for TA97). Only 2.2% (1/46) of the assays satisfied the evaluative criteria for hormesis. In conclusion, these data support a hormetic model for TA100, whereas the responses for TA97 and TA98 are consistent with a threshold dose-response model.

Predicting low dose effects for chemicals in high through-put studies.

High through-put studies commonly use automated systems with 96-well plates in which multiple chemicals are tested at multiple doses using log-2 dose increments after a suitable incubation period. There are typically multiple (ranging from five to eleven) doses on each chemical, and occasionally plate replications of the dose-response studies. The target endpoint for such studies is typically the LC50, but for some chemicals, there may be multiple doses below a benchmark dose where there is no apparent adverse response relative to control response. We show how an estimation approach can lead to clearly interpretable results about response in the low dose region using data from a high throughput study of 2189 chemicals on yeast. Accurate estimates can be obtained of response for study chemicals by using best linear unbiased predictors (BLUPs) in a mixed model, and summarized via plots with expected response (assuming no low-dose effect) with confidence intervals for response below the benchmark dose for each chemical, providing an informative summary of response at low doses. We conclude that this approach can provide valuable insights that would be missed if the observational data were only considered through the lens of statistical methods appropriate for experimental studies.

Bioavailability of arsenic in soil: pilot study results and design considerations.

Bioavailability of arsenic (As) from ingested soil is estimated in a two-period experimental study involving 11 subjects/period. In the first period, a 7-day mass-balance study measured As in food/beverages, urine, and stool to estimate bioavailability of As in food and beverages. Food/beverage As bioavailability (percentage ingested that is not in stool samples) is estimated as 91.0% with a 95% confidence interval given by (84.1%, 97.9%). In the second 7-day study period, subjects were placed on an As suppression diet. In the evening of day 2, each subject ingested a capsule containing 0.63 g of soil, including approximately 111.7 µg of soil-As. The bioavailability estimate of As from food and beverage ingestion during the first 2 days of the second period was 89.7%. Bioavailability of soil-As was estimated over the 5-day period following capsule ingestion, accounting for estimated bioavailability of food/beverage As. Assuming analytic recovery rates of As from combined soil and food/beverage samples are equal, soil-As bioavailability is estimated as 48.7% (95% CI [36.2%, 61.3%]). Relative to bioavailability of As from food/beverage sources, soil-As is estimated to be 54.3% (95% CI [40.3%, 68.4%]) as bioavailable.

Hormesis in high-throughput screening of antibacterial compounds in E coli.

This article assesses the response below a toxicological threshold for 1888 antibacterial agents in Escherichia coli, using 11 concentrations with twofold concentration spacing in a high-throughput study. The data set had important strengths such as low variability in the control (2%-3% SD), a repeat measure of all wells, and a built-in replication. Bacterial growth at concentrations below the toxic threshold is significantly greater than that in the controls, consistent with a hormetic concentration response. These findings, along with analyses of published literature and complementary evaluations of concentration-response model predictions of low-concentration effects in yeast, indicate a lack of support for the broadly and historically accepted threshold model for responses to concentrations below the toxic threshold.

Quantification of hormesis in anticancer-agent dose-responses.

Quantitative features of dose responses were analyzed for 2,189 candidate anticancer agents in 13 strains of yeast (Saccharomyces cerevisiae). The agents represent a diverse class of chemical compounds including mustards, other alkylating agents, and antimetabolites, inter alia. Previous analyses have shown that the responses below the toxic threshold were stimulatory and poorly predicted by a threshold dose-response model, while better explained by a hormetic dose-response model. We determined the quantitative features of the hormetic concentration-responses (n = 4,548) using previously published entry and evaluative criteria. The quantitative features that are described are: (1) the width of the concentration range showing stimulation above 10% of the control (mean of 5-fold), (2) the maximum stimulation of the concentration-responses (mean of 27% above the control), and (3) the width from the maximum stimulation to the toxicological threshold (mean of 3.7-fold). These results show that 52.5% of the 2,189 chemicals evaluated display hormetic concentration-responses in at least one of the 13 yeast strains. Many chemicals showed hormesis in multiple strains, and 24 agents showed hormesis in all 13 strains. The data are compared to previously reported quantitative features of hormesis based on published literature.

Seasonal and sex variation of high-sensitivity C-reactive protein in healthy adults: a longitudinal study.

BACKGROUND: Cross-sectional studies have reported seasonal variation in high-sensitivity C-reactive protein (hsCRP). However, longitudinal data are lacking. METHODS: We collected data on diet, physical activity, psychosocial factors, physiology, and anthropometric measurements from 534 healthy adults (mean age 48 years, 48.5% women, 87% white) at quarterly intervals over a 1-year period between 1994 and 1998. Using sinusoidal regression models, we estimated peak-to-trough amplitude and phase of the peaks. RESULTS: At baseline, average hsCRP was 1.72 mg/L (men, 1.75 mg/L; women, 1.68 mg/L). Overall seasonal variation amplitude was 0.16 mg/L (95% CI 0.02 to 0.30) and was lower in men (0.10 mg/L, 95% CI -0.11 to 0.31) than in women (0.23 mg/L, 95% CI 0.04 to 0.42). In both sexes, hsCRP peaked in November, with a corresponding trough in May. Relative plasma volume, waist and hip circumference, diastolic blood pressure, and depression scores were major factors associated with changes in amplitude of seasonal variation of hsCRP, and taken together explain most of the observed seasonal change. There was a 20% increase in the percentage of participants classified in the high-risk category for hsCRP (> or =3 mg/L) during late fall and early winter compared with late spring and early summer. CONCLUSIONS: Concentrations of hsCRP were modestly increased in fall and winter compared to summer, with greater seasonal amplitude of variation observed in women. Conventional classification methods fail to consider seasonality in hsCRP and may result in substantial misclassifications in the spring and fall. Future clinical practice and research should take these variations into account.

Hormesis predicts low-dose responses better than threshold models.

This study evaluated characteristics of the concentration-response relationships of chemicals from the U.S. National Cancer Institute (NCI) Yeast Anticancer Drug Screen database with respect to the threshold and the hormetic dose-response models. The database reported concentration-response studies of 2189 chemicals from a broad range of chemical classes. The biological end point was growth in 13 strains of yeast (Saccharomyces cerevisiae), most of which contain genetic alterations affecting DNA repair or cell cycle control. The analysis was limited to studies that satisfied a priori entry criteria for evaluation, including having two or more concentrations in the nontoxic zone (below a Benchmark Dose). The mean growth response compared to untreated controls of these doses was significantly greater than 100% in all 13 yeast strains, ranging from approximately 105% to approximately 111%. Under a threshold model, one would expect values more closely approximating 100%. Moreover, the distribution of responses below the BMD5 for chemicals was shifted upwardly from the expectations of a threshold model for all strains. These results indicate that for the chemicals and yeast strains studied, the responses are more consistent with a hormetic model than a threshold model, and they strengthen previous results presented by Calabrese et al. (2006, Toxicol. Sci. 94:368-378). Taken together, the analyses provide strong evidence for hormesis, a phenomenon with a broad range of biomedical and toxicological implications.

Association between dietary glycemic index, glycemic load, and high-sensitivity C-reactive protein.

OBJECTIVE: This study examined the relation between quality of dietary carbohydrate intake, as measured by glycemic index (GI) and glycemic load (GL), and serum high-sensitivity C-reactive protein (hs-CRP) levels. METHODS: During a 1-y observational study, data were collected at baseline and at each quarter thereafter. GI and GL were calculated from multiple 24-h dietary recalls (24HRs), 3 randomly selected 24HRs at every quarter, with up to 15 24HRs per participant. The hs-CRP was measured in blood samples collected at baseline and each of the four quarterly measurement points. Multivariable linear mixed models were used to examine the cross-sectional and longitudinal associations of GI, GL, and hs-CRP. RESULTS: Among 582 adult men and women with at least two measurements of diet and hs-CRP, average daily GI score (white bread = 100) was 85 and average GL was 198, and average hs-CRP was 1.84 mg/L. Overall, there was no association between GI or GL and hs-CRP. Subgroup analyses revealed an inverse association between GL and hs-CRP among obese individuals (body mass index > or =30 kg/m(2)). CONCLUSION: Quality of dietary carbohydrates does not appear to be associated with serum hs-CRP levels. Among obese individuals, higher dietary GL appears to be related to lower hs-CRP levels. Due to the limited number of studies on this topic and their conflicting results, further investigation is warranted.

Performance of Balanced Two-Stage Empirical Predictors of Realized Cluster Latent Values from Finite Populations: A Simulation Study.

Predictors of random effects are usually based on the popular mixed effects model developed under the assumption that the sample is obtained from a conceptual infinite population; such predictors are employed even when the actual population is finite. Two alternatives that incorporate the finite nature of the population are obtained from the superpopulation model proposed by Scott and Smith (1969, JASA, 64: 830-840) or from the finite population mixed model recently proposed by Stanek and Singer (2004, JASA, 99:1119-1130). Predictors derived under the latter model with the additional assumptions that all variance components are known and that within-cluster variances are equal have smaller mean squared error than the competitors based on either the mixed effects or Scott and Smith's models. As population variances are rarely known, we propose method of moment estimators to obtain empirical predictors and conduct a simulation study to evaluate their performance. The results suggest that the finite population mixed model empirical predictor is more stable than its competitors since, in terms of mean squared error, it is either the best or the second best and when second best, its performance lies within acceptable limits. When both cluster and unit intra-class correlation coefficients are very high (e.g., 0.95 or more), the performance of the empirical predictors derived under the three models is similar.