Cross-platform proteomics signatures of extreme old age.

In previous work we used a Somalogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals.

Outcome Comparison of Transconjunctival Müller's Muscle Recession With Levator Disinsertion (TMRLD) to Gold Weight Implantation in the Treatment of Paralytic Lagophthalmos.

PURPOSE: To compare clinical outcomes of transconjunctival Müller's muscle recession with levator disinsertion (TMRLD) to the traditional gold weight implantation in patients with paralytic lagophthalmos. METHODS: A retrospective nonrandomized comparative review of patients who had gold weight implantation and TMRLD surgeries for paralytic lagophthalmos from January 2016 to January 2023 was performed. The main outcome comparisons were measurement changes in lagophthalmos, marginal reflex distance 1, visual acuity, and corneal examination. Complication and reoperation rates were also compared. RESULTS: Twenty-six cases of gold weight implantation and 20 cases of TMRLD surgeries were identified. The changes in logMAR visual acuity between gold weight implantation and TMRLD groups were not statistically significant (-0.10 ± 0.48 vs. +0.05 ± 0.14, p > 0.05). The percent improvement in lagophthalmos (62.2% ± 51.8% vs. 58.4% ± 21.1%) and final marginal reflex distance 1 (2.22 ± 1.42 vs. 2.25 ± 1.41 mm) were also comparable between groups ( p > 0.05). Both groups showed similar changes in marginal reflex distance 1 (1.75 ± 1.31 vs. 2.83 ± 1.37 mm) and lagophthalmos (3.77 ± 3.92 vs. 3.36 ± 1.36 mm) ( p > 0.05). The overall complication (15.4% vs. 15.0%) and reoperation rates (15.4% vs. 15.0%) were comparable over the follow-up duration (291.6 ± 437.3 vs. 121.0 ± 177.8 days) ( p > 0.05). CONCLUSION: TMRLD is as safe and effective as the gold weight implantation in addressing paralytic lagophthalmos in patients with facial nerve palsy.

State Alcohol Policy Environments of U.S. Colleges: Predictors of Sexual Assault and Alcohol-Related Arrest and Disciplinary Action.

INTRODUCTION: Binge drinking and sexual assault are serious inter-related public health problems faced by college students. State-level alcohol policy restrictiveness has been found to decrease binge drinking among college students and, therefore, may also reduce occurrences of alcohol-related criminal offenses. It was hypothesized that more restrictive state alcohol policy environments would be associated with fewer liquor law violations and sexual assault offenses on U.S. college campuses. METHODS: Data were aggregated across 3 academic years (2016-2017, 2017-2018, and 2018-2019) and represented n=1,290 institutions. Zero-inflated negative binomial regression modeling was performed in 2022-2023 to evaluate associations of state-level young adult binge drinking and the Alcohol Policy Scale (APS) with the numbers of campus-level alcohol-related arrests, alcohol-related disciplinary actions, rape offenses, and fondling offenses reported in national Campus Safety and Security data. RESULTS: Higher APS scores had direct associations with fewer alcohol-related arrests (1.79% decrease per one-unit increase in APS, p=0.05), alcohol-related disciplinary actions (2.27% decrease per one-unit increase in APS, p=0.027), and rape offenses (0.85% decrease per one-unit increase in APS, p=0.021). The associations APS scores had with disciplinary actions and rape offenses were partially and fully mediated, respectively, by state-level young adult binge drinking. No associations were found between APS and fondling offenses. CONCLUSIONS: This cross-sectional study presents evidence that more restrictive state alcohol policies are associated with fewer alcohol-related arrests and disciplinary actions, and rape offenses on college campuses. Future research should identify the alcohol policy domains that are most protective against these outcomes.

Preseptal transconjunctival approach in orbital floor fracture repairs to prevent postoperative lower eyelid malposition.

PURPOSE: Lower eyelid malposition can be a complication following orbital floor fracture surgeries. We present our incidence of lower eyelid malposition from a large case series of orbital floor fracture repairs using the 'swinging eyelid' approach and 'hang back' technique. METHODS: A retrospective review of all orbital fracture surgeries at our institution from November 2011 to March 2021 was performed. Primary outcomes included the incidence of lower eyelid malposition by category, the average time to presentation after primary surgery, and reoperation rates among cases with lower eyelid complications. RESULTS: A total of 438 cases that involved repair of the fractured orbital floor were identified. Six patients (1.37 %) developed lower eyelid malposition following primary orbital floor repair. Two patients (0.46 %) developed reverse ptosis of the lower eyelid. Two patients (0.46 %) returned with lower lid cicatricial ectropion. One patient (0.23 %) had postoperative lower eyelid retraction. One patient (0.23 %) had postoperative lower eyelid cicatricial entropion. No cases of lower lid flattening, lower eyelid fat flattening, or eyelid notch was noted. All patients with lower eyelid malposition underwent additional surgeries except one patient with reverse ptosis (83.3 %). The average time to the presentation of postoperative complications from the surgery date was 292.8 days (range = 49 days to 3.5 years). CONCLUSION: Lower eyelid malposition after orbital floor repair is a known complication that can be decreased by employing the 'swinging eyelid' with a preseptal approach and closure by the 'hang back' technique.

Cannabis and Alcohol Use by U.S. Young Adults, 2008-2019: Changes in Prevalence After Recreational Cannabis Legalization.

INTRODUCTION: Young adults' cannabis and alcohol use patterns have changed after state recreational cannabis legalization according to studies based on college samples but not nationally representative samples. Associations between recreational cannabis legalization and changes in cannabis and alcohol use outcomes among young adults were examined, including differences by college enrollment and minor status (ages 18-20 vs 21-23 years). METHODS: Repeated cross-sectional data (2008-2019) were collected from college-eligible participants aged 18-23 years in the National Survey on Drug Use and Health. Self-reported past-month cannabis use and frequent use (≥20 days) and a proxy for past-year DSM-5 cannabis use disorder were primary outcomes; past-month frequent alcohol use and binge drinking were secondary outcomes. Multilevel logistic regression models quantified changes in outcome prevalence from the study years before to after recreational cannabis legalization, adjusting for secular trends. Analyses were conducted on March 22, 2022. RESULTS: Prevalence increased from before to after recreational cannabis legalization for past-month cannabis use (from 21% to 25%) and past-year proxy cannabis use disorder (from 11% to 13%); the increases were statistically significant [adjusted odds ratio (95% CI) = 1.20 (1.08-1.32) and 1.14 (1.003-1.30), respectively]. Increases were detected for young adults who were not in college and who were aged 21-23 years. Recreational cannabis legalization impacts were not detected for secondary outcomes. CONCLUSIONS: Some young adults appear sensitive to state recreational cannabis legalization, including in terms of cannabis use disorder risk. Additional prevention efforts should be directed to young adults who are not in college and timed to occur before age 21 years.

Comparing National College Health Assessment with other surveys of cannabis use and binge drinking among young adult college students 2008-2018.

Objective: We considered the utility of National College Health Assessment (NCHA) data relative to other national data for studying college students' cannabis use and binge drinking, and drug policy effects. Participants: Survey data on 18-22-year old college students were drawn from the 2008-2018 NCHA, National Survey on Drug Use and Health (NSDUH), Monitoring the Future (MTF), and Healthy Minds Study (HMS). Methods: Prevalence estimates were compared across data sources in terms of level and change from 2008-2018 using linear regressions, separately for men and women. Results: Mean prevalence estimates for 30-day cannabis use and 2-week binge drinking, and linear time trends did not differ significantly among NCHA, NSDUH, and MTF. Conclusions: NCHA prevalence estimates are similar to those from NSDUH and MTF, NCHA has unique strengths, and some weaknesses can be offset. Findings support the value of NCHA for studying college students' substance use and effects of drug policy.

Psychosocial functioning associated with prescription stimulant and opioid misuse versus illicit drug use among college students.

Objective: College students' prescription stimulant and opioid misuse (PSM and POM) share psychosocial risks with other substance use. We sought to extend a prior study of these issues. Methods: National College Health Assessment (2015-2016) participants ages 18-24 years (n = 79,336) reporting 12-month PSM (defined as use of a drug not prescribed to them), 30-day other illicit drug use (non-cannabis), both, or neither, were compared on other substance use, psychopathology, academic adjustment, attention deficit hyperactivity disorder, and chronic pain. Models were repeated for POM. Results: Relative to those who only misused the prescription drug, those who used other illicit drugs had lower odds of chronic pain and academic problems, but higher odds on nearly every other outcome especially if they also misused the prescription drug. Conclusions: Findings suggest PSM and POM are on a continuum of risk shared with illicit drug use, but also are linked to outcomes specific to these drugs' perceived medical purposes.

Evaluation of GENESIS, SAIGE, REGENIE and fastGWA-GLMM for genome-wide association studies of binary traits in correlated data.

Performing a genome-wide association study (GWAS) with a binary phenotype using family data is a challenging task. Using linear mixed effects models is typically unsuitable for binary traits, and numerical approximations of the likelihood function may not work well with rare genetic variants with small counts. Additionally, imbalance in the case-control ratios poses challenges as traditional statistical methods such as the Score test or Wald test perform poorly in this setting. In the last couple of years, several methods have been proposed to better approximate the likelihood function of a mixed effects logistic regression model that uses Saddle Point Approximation (SPA). SPA adjustment has recently been implemented in multiple software, including GENESIS, SAIGE, REGENIE and fastGWA-GLMM: four increasingly popular tools to perform GWAS of binary traits. We compare Score and SPA tests using real family data to evaluate computational efficiency and the agreement of the results. Additionally, we compare various ways to adjust for family relatedness, such as sparse and full genetic relationship matrices (GRM) and polygenic effect estimates. We use the New England Centenarian Study imputed genotype data and the Long Life Family Study whole-genome sequencing data and the binary phenotype of human extreme longevity to compare the agreement of the results and tools' computational performance. The evaluation suggests that REGENIE might not be a good choice when analyzing correlated data of a small size. fastGWA-GLMM is the most computationally efficient compared to the other three tools, but it appears to be overly conservative when applied to family-based data. GENESIS, SAIGE and fastGWA-GLMM produced similar, although not identical, results, with SPA adjustment performing better than Score tests. Our evaluation also demonstrates the importance of adjusting by full GRM in highly correlated datasets when using GENESIS or SAIGE.

The impact of wildfire smoke and temperature on traumatic worker injury claims, Oregon 2009-2018.

Background and Aims: As average temperatures rise and wildfire events increase in the United States, outdoor workers may be at an increased risk of injury. Recent research suggests that heat exposure increases outdoor workers' risk of traumatic injuries, but co-exposures of heat and wildfire smoke have not been evaluated. Methods: Oregon workers' compensation data from 2009 to 2018 were linked to satellite data by the date of injury to determine if acute heat (maximum Heat Index) and wildfire smoke (presence/absence) were associated with a traumatic injury. North American Industry Classification System (NAICS) codes were utilized to identify accepted, disabling injury claims from construction (NAICS 23) and agriculture, forestry, fishing, and hunting (NAICS 11). Claims from April to October were analyzed using negative binomial models to calculate incident rate ratios (IRR) by heat and wildfire exposure for All workers and specifically for Agricultural (Ag)/Construction workers. Results: During the study period, 91,895 accepted, traumatic injury claims were analyzed. All workers had an injury IRR of 1.04 (95% confidence interval [CI]: 1.02-1.06) while Ag/Construction workers had an IRR of 1.11 (95% CI: 1.06-1.16) when wildfire smoke was present. When the maximum Heat Index was 75°F or greater, the IRR significantly increased as temperatures increased. When the maximum Heat Index was above 80-84°F, All workers had an IRR of 1.04 (95% CI: 1.01-1.06) while Ag/construction workers had an IRR of 1.14 (95% CI: 1.08-1.21) with risk increasing with increased temperatures. In joint models, heat remained associated with injury rates, but not wildfire smoke. No multiplicative interactions between exposures were observed. Conclusion: Increasing temperature was associated with increased rates of traumatic injury claims in Oregon that were more pronounced in Ag/Construction workers. Future work should focus on further understanding these associations and effective injury prevention strategies.

Silicone Sphere Implant Extrusion From Orbital Granulomatosis With Polyangiitis: A Rare Complication in the Anophthalmic Socket.

Orbital implant extrusion is a known complication following evisceration and enucleation. In this case report, we present a 45-year-old woman who presented with a left silicone implant exposure and infection 2 years following evisceration with saddle nose on examination. CT of the maxillofacial bones without contrast showed bilateral soft tissue infiltration around the superior recti muscles, as well as a nasal septum perforation from extensive sinus disease. Left orbitotomy revealed a small fibrotic mass near the orbital roof. Biopsy and serology results were consistent with granulomatosis with polyangiitis.

Association between late maternal age and age-related endophenotypes in the Long Life Family Study.

Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibit healthier endophenotype profiles compared to younger mothers. The association between maternal age and age-related endophenotypes previously derived in LLFS was assessed using Generalized Estimating Equations to adjust for relatedness. The quartiles of the maternal age at last childbirth were modeled as the independent variables. Univariate analyses tested the association between maternal age at last childbirth and age at clinical assessment, education, field center, Apolipoprotein E (APOE) genotype, depression, stress, smoking and successful pregnancies. Only the variables significantly associated in the univariate analyses were considered in secondary multivariate analyses. Univariate analyses showed that compared to older mothers (age at last birth ≥35), mothers 30 years old or younger at last childbirth are less educated (12 ± 3 years versus 13 ± 3 years) and have a higher frequency of smoking (9% versus 3% for maternal age ≥35). Results showed that older mothers (age at last birth ≥31-34 or ≥ 35) demonstrated significantly better cognitive profiles (p = 0.017 and p = 0.021 respectively) compared with mothers with last childbirth age ≤30. Later maternal age among women from long-life families is associated with a better cognitive profile, supporting the hypothesis that later age at childbirth may be a marker for healthy aging.

Impact of acute temperature and air pollution exposures on adult lung function: A panel study of asthmatics.

BACKGROUND: Individuals with respiratory conditions, such as asthma, are particularly susceptible to adverse health effects associated with higher levels of ambient air pollution and temperature. This study evaluates whether hourly levels of fine particulate matter (PM2.5) and dry bulb globe temperature (DBGT) are associated with the lung function of adult participants with asthma. METHODS AND FINDINGS: Global positioning system (GPS) location, respiratory function (measured as forced expiratory volume at 1 second (FEV1)), and self-reports of asthma medication usage and symptoms were collected as part of the Exposure, Location, and Lung Function (ELF) study. Hourly ambient PM2.5 and DBGT exposures were estimated by integrating air quality and temperature public records with time-activity patterns using GPS coordinates for each participant (n = 35). The relationships between acute PM2.5, DBGT, rescue bronchodilator use, and lung function collected in one week periods and over two seasons (summer/winter) were analyzed by multivariate regression, using different exposure time frames. In separate models, increasing levels in PM2.5, but not DBGT, were associated with rescue bronchodilator use. Conversely DBGT, but not PM2.5, had a significant association with FEV1. When DBGT and PM2.5 exposures were placed in the same model, the strongest association between cumulative PM2.5 exposures and the use of rescue bronchodilator was identified at the 0-24 hours (OR = 1.030; 95% CI = 1.012-1.049; p-value = 0.001) and 0-48 hours (OR = 1.030; 95% CI = 1.013-1.057; p-value = 0.001) prior to lung function measure. Conversely, DBGT exposure at 0 hours (ß = 3.257; SE = 0.879; p-value>0.001) and 0-6 hours (ß = 2.885; SE = 0.903; p-value = 0.001) hours before a reading were associated with FEV1. No significant interactions between DBGT and PM2.5 were observed for rescue bronchodilator use or FEV1. CONCLUSIONS: Short-term increases in PM2.5 were associated with increased rescue bronchodilator use, while DBGT was associated with higher lung function (i.e. FEV1). Further studies are needed to continue to elucidate the mechanisms of acute exposure to PM2.5 and DBGT on lung function in asthmatics.

Acute Bilateral Vision Loss Following Unilateral Optic Nerve Sheath Fenestration.

Optic nerve sheath fenestration (ONSF) is a surgical technique commonly and effectively employed in the treatment of recalcitrant, vision-threatening papilledema. Unilateral blindness, a known risk of unilateral ONSF widely cited with 1%-2% incidence. In this case, a 58-year-old patient who presented symptomatic with bilateral hemorrhagic papilledema unresponsive to medical therapy underwent uneventful unilateral ONSF via standard superomedial eyelid crease incision. The patient presented postoperatively with severe bilateral vision loss. Workup revealed widespread metastatic malignant disease involving the optic chiasm and optic nerve sheath.

Evaluation of vertical and multi-axial suspension seats for reducing vertical-dominant and multi-axial whole body vibration and associated neck and low back joint torque and muscle activity.

The primary aim of this laboratory-based human subject study was to evaluate the biomechanical loading associated with mining vehicles' multi-axial whole body vibration (WBV) by comparing joint torque and muscle activity in the neck and low back during three vibration conditions: mining vehicles' multi-axial, on-road vehicles' vertical-dominant, and no vibration. Moreover, the secondary aim was to determine the efficacy of a vertical passive air suspension and a prototype multi-axial active suspension seat in reducing WBV exposures and associated biomechanical loading measures. The peak joint torque and muscle activity in the neck and low back were higher when exposed to multi-axial vibration compared to the vertical-dominant or no vibration condition. When comparing the two suspension seats, there were limited differences in WBV, joint torque, and muscle activity. These results indicate that there is a need to develop more effective engineering controls to lower exposures to multi-axial WBV and related biomechanical loading. Practitioner Summary: This study found that mining vehicles' multi-axial WBV can increase biomechanical loading in the neck and back more so than on-road vehicles' vertical-dominant WBV. While a newly-developed multi-axial active suspension seat slightly reduced the overall WBV exposures, the results indicate that more effective engineering controls should be developed. Abbreviation: APDF: amplitude probability density function; Aw: weighted average vibration; BMI: body mass index; C7: The 7th cervical vertebra; EMG: electromyography; ES: erector spinae; IRB: institutional review board; ISO: International Organization for Standardization; L5/S1: the fifth lumbar vertebra (L5)/the first sacral vertebra(S1); MSDs: musculoskeletal disorders; MVC: maximum voluntary contraction; PSD: power spectral density; RVC: reference voluntary contraction; SCM: sternocleidomastoid; SD: standard deviation; SPL: splenius capitis; TRAP: trapezius; VDV: vibration dose value; WBV: whole body vibration.

A Genome-Wide Association Study of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants.

We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609, p = 7.13 × 10-8) that almost reached genome-wide significance and four additional loci that were suggestively significant. Among these, a novel rare variant (rs145265196) on chromosome 11 had much higher longevity allele frequencies in cases of Ashkenazi Jewish and Southern Italian ancestry compared to cases of other European ancestries. We also correlated EL-associated SNPs with serum proteins to link our findings to potential biological mechanisms that may be related to EL and are under genetic regulation. The findings from the proteomic analyses suggested that longevity-promoting alleles of significant genetic variants either provided EL cases with more youthful molecular profiles compared to controls or provided some form of protection from other illnesses, such as Alzheimer's disease, and disease progressions.

Enhancing gender and ethnic representativeness of NCHA-II data with survey weights: The examples of substance use prevalence and state marijuana legalization.

OBJECTIVE: We evaluated how applying post-stratification sampling weights to National College Health Assessment II (NCHA-II) data affects estimates of substance use prevalence and tests of medical and recreational marijuana legalization (MML and RML) effects. Participants/Methods: We constructed weights for Fall 2015 and Spring 2016 surveys (n = 90,503) using population information on U.S. undergraduates' gender and race/ethnicity and three institutional characteristics (region, city population, public/private). We estimated substance use prevalence (e.g., e-cigarettes, prescription opioid misuse) and compared 30-day marijuana use rates in states with RML, MML, or neither policy. Results: When unweighted versus weighted data were used, prevalence estimates did not differ appreciably; conclusions from logistic regressions were similar (weighted 30-day marijuana use rates among undergraduates in RML, MML, and non-ML states were 30.0%, 20.3%, and 16.3%, respectively) but effect sizes differed. Conclusions: The value of using weighted NCHA-II data depends on the analysis and the precision required for the research questions.

Trends in college students' alcohol, nicotine, prescription opioid and other drug use after recreational marijuana legalization: 2008-2018.

BACKGROUND: Young adult college students may be particularly sensitive to recreational marijuana legalization (RML). Although evidence indicates the prevalence of marijuana use among college students increased after states instituted RML, there have been few national studies investigating changes in college students' other substance use post-RML. METHOD: The cross-sectional National College Health Assessment-II survey was administered twice yearly from 2008 to 2018 at four-year colleges and universities. Participants were 18-26 year old undergraduates attending college in states that did (n = 243,160) or did not (n = 624,342) implement RML by 2018. Outcome variables were self-reported nicotine use, binge drinking, illicit drug use, and misuse of prescription stimulants, sedatives, and opioids. Other variables included individual and contextual covariates, and institution-reported institutional and community covariates. Publicly available information was used to code state RML status at each survey administration. RESULTS: Accounting for state differences and time trends, RML was associated with decreased binge drinking prevalence among college students age 21 and older [OR (95% CI) = 0.91 (0.87 - 0.95), p < .0001] and increased sedative misuse among minors [OR (95% CI) = 1.20 (1.09 - 1.32), p = .0003]. RML did not disrupt secular trends in other substance use. CONCLUSIONS: In the context of related research showing national increases in college students' marijuana use prevalence and relative increases following state RML, we observed decreases in binge drinking and increases in sedative use that both depended on age. Findings support some specificity in RML-related changes in substance use trends and the importance of individual factors.

Marijuana use trends among college students in states with and without legalization of recreational use: initial and longer-term changes from 2008 to 2018.

BACKGROUND AND AIMS: Young adult college students in the United States are likely to be affected by marijuana liberalization trends. However, changes in students' marijuana use following recreational marijuana legalization (RML) have not been examined in more than one RML state at a time, or beyond 1-2 years post-legalization. DESIGN: Cross-sectional National College Health Assessment survey administered twice yearly from 2008 to 2018. SETTING: A total of 587 4-year colleges and universities in 48 US states. PARTICIPANTS: Undergraduates aged 18-26 years attending college in US states that did (n = 234 669 in seven states) or did not (n = 599 605 in 41 states) enact RML between 2008 and 2018. MEASUREMENTS: Self-reported marijuana use (past 30 days) and individual and contextual covariates, institution-provided institutional and community covariates and publicly available dates when states enacted RML. FINDINGS: Adjusting for covariates, state differences and state-specific linear time trends (accounting for pre-RML trends), prevalence of 30-day marijuana use increased more among students exposed to RML [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.19-1.28, P < 0.001] than among non-RML state students throughout the same time-period; the results were similar for frequent use (≥ 20 days) (OR = 1.18, 95% CI = 1.10-1.27, P < 0.001). Interaction models supported stronger RML effects among students who were female, residing off-campus and aged 21 years and older; sexual orientation did not moderate RML effects. In the earliest states to enact RML (2012) there were increases in use prevalence in the second through the sixth year post-RML compared to pre-RML. In the second legalization group (2015) there were increases in the first and second year post-RML, and greater increases in the third year. In the later states (2016-17), increases were observed in both years after RML. CONCLUSIONS: In US states that enacted recreational marijuana legislation from 2012 to 2017 there was evidence for a general trend towards greater increases in marijuana use by college students and differential impact by gender, legal using age and campus residence.

Genetic associations with age of menopause in familial longevity.

OBJECTIVE: We hypothesize that mechanisms associated with extended reproductive age may overlap with mechanisms for the selection of genetic variants that slow aging and decrease risk for age-related diseases. Therefore, the goal of this analysis is to search for genetic variants associated with delayed age of menopause (AOM) among women in a study of familial longevity. METHODS: We performed a meta-analysis of genome-wide association studies for AOM in 1,286 women in the Long Life Family Study (LLFS) and 3,151 women in the Health and Retirement Study, and then sought replication in the Framingham Heart Study (FHS). We used Cox proportional hazard regression of AOM to account for censoring, with a robust variance estimator to adjust for within familial relations. RESULTS: In the meta-analysis, a single nucleotide polymorphism (SNP) previously associated with AOM reached genome-wide significance (rs16991615; HR = 0.74, P = 6.99 × 10). A total of 35 variants reached >10 level of significance and replicated in the FHS and in a 2015 large meta-analysis (ReproGen Consortium). We also identified several novel SNPs associated with AOM including rs3094005: MICB, rs13196892: TXNDC5 | MUTED, rs72774935: SSBP2 | ATG10, rs9447453: COL12A1, rs114298934: FHL2 | NCK2, rs6467223: TNPO3, rs9666274 and rs10766593: NAV2, and rs7281846: HSPA13. CONCLUSIONS: This work indicates novel associations and replicates known associations between genetic variants and AOM. A number of these associations make sense for their roles in aging. VIDEO SUMMARY: Supplemental Digital Content 1, http://links.lww.com/MENO/A420.

Perceived prevalence of peer marijuana use: changes among college students before and after Oregon recreational marijuana legalization.

Background: Oregon students' rates of marijuana use have increased following recreational marijuana legalization (RML), but the relation between RML and students' perceived peer use of marijuana - or descriptive norms - is unknown. Objectives: This study examined whether perceived peer use of marijuana changed more following RML for college students in Oregon than in states without RML. Methods: Repeated cross-sectional data were collected from the National College Health Assessment-II surveys from 2008 to 2016 to assess changes in descriptive norms ("Within the last 30 days, what percent of students at your school used marijuana?") among 18-26 year-old undergraduates from two Oregon institutions and 123 institutions in non-RML states (N = 280,006; 66.23% female; 33.19% male) following Oregon RML (7/1/2015). Mixed-effects regressions were used to account for clustering at the institutional level; models controlled for covariates and secular changes in descriptive norms. Results: RML was associated with higher perceived rates of marijuana use by peers [Percent Increase = 3.09, p < .001]. The effect was significant for respondents who had never used marijuana [Percent Increase = 3.72, p < .001], but not for respondents who recently or ever previously used marijuana. Respondents who had recently used marijuana had higher descriptive norms than those who had never used [Percent Increase = 12.83, p < .001]. Conclusions: Given the association between descriptive norms and personal use, RML-related increases in descriptive norms among non-using students could contribute to future marijuana use initiation and may be one mechanism linking RML with higher rates of marijuana use among college students.