Standard Deviation Units Research Articles

Abstract 7320: Expression of circadian rhythm genes and lethal prostate cancer

Abstract Background: The circadian rhythm regulates diverse physiological and oncologic processes. We have previously shown in epidemiology studies that disruption of the circadian rhythm may be associated with increased risk of aggressive prostate cancer, including germline polymorphisms in certain circadian rhythm genes. This study sought to investigate the relationship between tumor circadian rhythm gene expression and lethal prostate cancer. Methods: We studied patients with primary prostate cancer in the Health Professionals Follow-up Study (HPFS) and Physicians’ Health Study (PHS). We created a composite score of mRNA expression using principal components that incorporated 11 circadian rhythm genes: AANAT, ARNTL, CLOCK, CRY1, CSNK1E, MTNR1A, MTNR1B, NPAS2, PER1, PER2, PER3. An age-stratified analysis was performed, and the mean differences of the score both by Gleason score and compared to normal tissue were calculated. The relationship between the score in prostate tumor tissue and lethal prostate cancer (metastases/prostate cancer-specific death) vs. indolent disease (no metastases after >8 years of follow-up) was assessed using logistic regression. The contribution of each gene was evaluated by leave-one-out analysis, generating scores leaving out one gene and assessing the relationship between the modified score and lethal disease. Results: Among 404 cancer patients in HPFS/PHS, there were 119 lethal events over 30 years of follow-up (median: 17 years). The circadian rhythm gene score was lower in tumor tissue compared to tumor-adjacent, histologically normal tissue (mean difference in units of standard deviation [SD] of gene score: -0.31, 95% confidence interval [CI]: -0.48 to -0.15). In addition, the score was lower in Gleason 9-10 compared to Gleason 6 tumors (mean difference in SD units: -1.05, 95% CI: -1.55 to -0.54). The three PER genes were the most strongly correlated with each other and with the score (Spearman correlation coefficients from 0.52-0.88 for the score and 0.31-0.63 between PER genes). Higher circadian rhythm gene scores were inversely associated with lethal prostate cancer (odds ratio [OR] for highest vs. lowest quartile: 0.43, 95% CI: 0.20 to 0.90) in a dose-response fashion and after adjusting for clinical and pathologic factors. The association appeared to be stronger in patients aged ≥65 years (OR for highest vs. lowest quartile: 0.21, 95% CI: 0.08 to 0.47) compared to <65 years at diagnosis (OR: 0.78, 95% CI: 0.29, 2.17). Results were consistent in the leave-one-out analysis for all genes except PER2 (OR for highest vs. lowest quartile: 1.00, 95% CI: 0.55 to 1.83) and PER1 (OR: 0.55, 95% CI: 0.30 to 1). Conclusion: This study examining intratumoral circadian rhythm gene expression contributes further evidence in support of the relationship between circadian rhythm disruption and aggressive prostate cancer. Tumor expression of PER1 and PER2 may be a predominant factor in the association. Citation Format: Jane Bailey Vaselkiv, Sarah C. Markt, Hannah E. Guard, Anqi Wang, Kathryn L. Penney, Konrad H. Stopsack, Lorelei A. Mucci. Expression of circadian rhythm genes and lethal prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7320.

Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study

Background & AimsGlucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.MethodsTwo-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.ResultsABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071–0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476–18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.ConclusionsSome glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study

High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002–0.067); p = 0.036) and “a body shape index” (ABSI; 0.039 (0.006–0.071); p = 0.021). There was no evidence for associations with hip index (HI) or body mass index (BMI). Among individual polymorphisms, rs7450600 stood out (chromosome 6; Long Intergenic Non-Protein-Coding RNA 473 gene, LINC00473). Morning plasma cortisol proxied by rs7450600 was associated positively with WHI and inversely with HI and BMI in women and men. Our findings support a causal association of higher morning plasma cortisol with larger waist size in women and highlight LINC00473 as a genetic link between morning plasma cortisol and body shape.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS

BackgroundLonger effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline. ObjectivesThis study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition. MethodsCOSMOS is a 2 × 2 factorial trial of cocoa extract (500 mg flavanols/d) and/or a daily MVM supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests administered at baseline. For the meta-analysis, we included nonoverlapping participants across 3 COSMOS cognitive substudies: COSMOS-Clinic (n = 573); COSMOS-Mind (n = 2158); COSMOS-Web (n = 2472). ResultsIn COSMOS-Clinic, we observed a modest benefit of MVM compared with placebo on global cognition over 2 y {mean difference [95% confidence interval (CI)] = 0.06 SD units (SU) (−0.003, 0.13)}, with a significantly more favorable change in episodic memory [mean difference (95% CI) = 0.12 SU (0.002, 0.23)] but not in executive function or attention [mean difference (95% CI) = 0.04 SU (−0.04, 0.11)]. The meta-analysis of COSMOS substudies showed clear evidence of MVM benefits on global cognition [mean difference (95% CI) = 0.07 SU (0.03, 0.11); P = 0.0009] and episodic memory [mean difference (95% CI) = 0.06 SU (0.03, 0.10); P = 0.0007]; the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 y. ConclusionsIn COSMOS-Clinic, daily MVM supplementation leads to a significantly more favorable 2-y change in episodic memory. The meta-analysis within COSMOS cognitive substudies indicates that daily MVM significantly benefits both global cognition and episodic memory. These findings within the COSMOS trial support the benefits of a daily MVM in preventing cognitive decline among older adults.This trial was registered at COSMOS—clinicaltrials.gov as NCT02422745, at COSMOS-Mind—clinicaltrials.gov as NCT03035201, and at COSMOS-Web—clinicaltrials.gov as NCT04582617.

Distress about social problems and tobacco and cannabis use outcomes among young adults in Los Angeles County

ObjectiveTo examine associations of concern, worry, and stress about discrimination, shootings/violence, and police brutality and exclusive and dual tobacco and cannabis use among young adults. MethodsA prospective, racially/ethnically diverse cohort of young adults (n = 1960) living in Los Angeles, California completed a baseline survey in 2020 (age range: 19–23) and a follow-up survey in 2021. Exploratory factor analysis (EFA) was employed on nine variables assessing levels of concern, worry, and stress about societal discrimination, societal shootings/violence, and community police brutality at baseline. Past 30-day tobacco and cannabis use at follow-up was categorized as current exclusive tobacco, exclusive cannabis, and dual tobacco and cannabis (vs never/former) use based on eleven use variables. Multinomial logistic regressions estimated adjusted associations between each factor score (translated to standard deviation units) with exclusive and dual tobacco and cannabis use. ResultsThe EFA produced four factor scores representing concern/worry/stress (i.e., distress) about community police brutality (F1), distress about societal shootings/violence (F2), and distress about societal discrimination (F3), as well as generalized stress about police brutality, shootings/violence, and discrimination (F4). F1, F2, and F3 were associated with subsequent exclusive current cannabis use, with F1 having the strongest association (OR: 1.35, 95% CI: 1.18–1.55), while only F1 (OR: 1.51, 95% CI: 1.27–1.78) was associated with dual tobacco and cannabis use. None of the factors were associated with exclusive tobacco use. ConclusionsYoung adult concern, worry, and/or stress about social problems may increase risk of cannabis use with or without concurrent tobacco use 6–12 months later.

Standardized precipitation index analysis and drought frequency tendencies in lower eastern counties of Kenya

The standardized precipitation index (SPI) is a fundamental indicator of meteorological, hydrological, and agricultural droughts in the world. This study aims to evaluate different timescales, 3 months (SPI-3), 6 months (SPI-6), 9 months (SPI-9), and 12 months (SPI-12) indices from meteorological data in quantifying drought characterization in lower eastern counties of Kenya from 1990 to 2018 for observed data and from 1986 to 2018 for Climatic Research Unit Time Series (CRU) data. Precipitation in-situ data (annual) and high-resolution (0.5 × 0.5 degree grid) monthly-scale precipitation data were sought from Kenya Meteorological Department and CRU TS, respectively. Z-Score (SPI) was computed for each year (in-situ data) and month (CRU TS data) using the SPI algorithm, expressed as the departure from the mean in standard deviation units. Quality control of CRU TS data was done by checking outlier values and comparing the data with precipitation data obtained from the meteorological department as well as ERA5 reanalysis data. Results showed that extreme to mild drought was experienced across the Kenyan counties for both annual in-situ and monthly gridded data. Machakos county experienced a year of extreme drought, while Makueni and Taita-Taveta have had 2 and 4 years of severe droughts, respectively. The monthly SPI indices of 3, 6, 9, and 12 months showed a remarkably consistent behavioral pattern detecting extreme droughts across the counties. Considering the uncertainties, unpredictability, and shifting of the long and short rainy seasons in Kenya, results were obtained related to dry and wet episodes and to their relationship with agricultural production as well as water availability and environmental management.

Measuring the Efficacy of Zearn Math in Louisiana

This study examines the impact of an online math learning program on third through fifth grade math achievement in Louisiana. Employing Zearn Math usage metrics and administrative data from the Louisiana Department of Education, the results indicate that grade levels that programmatically used Zearn Math scored, on average, about .03 standard deviation units higher on Louisiana’s statewide math assessment. A placebo test using English-language arts scores and several robustness checks suggests that this may be an underestimate of the true effect. These findings come at a crucial time because pandemic-related school closures have led to a 20-fold increase in public school spending on Zearn-related materials between July 2019 and July 2021, and its presence continues to expand across the nation.

Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial

BackgroundSome prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. ObjectivesTo test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. MethodsThe COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (–)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. ResultsParticipants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: −0.01 (−0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): −0.01 (−0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (−0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. ConclusionsAmong 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. Trial registrationThis trial was registered at clinicaltrials.gov with identifier – NCT02422745.

Plasma Total‐Tau is Related to Risk of Heart Failure in the Community

AbstractBackgroundTau is mainly expressed in the neurons of the central nervous system, with elevated cerebrospinal fluid and plasma levels noted when pathologic extracellular aggregation of tau occurs in the setting of neurodegeneration. Plasma tau and phosphorylated tau species are currently being studied as biomarkers for diagnosis, prognosis, or to measure susceptibility risk for conditions such as Alzheimer’s disease. However, the potential for circulating tau protein or other toxic entities upstream or along the tau pathway to cause cardiac dysfunction via protein misfolding or abnormal aggregation has only received limited study.MethodsWe evaluated the association of plasma total‐tau and risk of congestive heart failure in a community‐based sample from the prospective Framingham Heart Study. Adult participants free from clinical heart failure at time of blood sample (Exam 8, 2005‐2008) were included. Participants with renal failure or on dialysis were excluded. Plasma total‐tau was measured using the Simoa platform. Total‐tau plasma values were natural log‐transformed to approximate a normal distribution. Using Cox regression models, total‐tau was related to incident congestive heart failure (up to 2019), adjusting for age and sex (Model 1) and additionally adjusting for cardiovascular risk factors: systolic blood pressure, prevalent diabetes, antihypertensive medication use, smoking status, total cholesterol‐to‐high density lipoprotein ratio, and prevalent atrial fibrillation (Model 2).ResultsWe studied 2792 participants (mean age 67±9 years, 55% women) over a mean follow‐up period of 10.7±3.2 years (Table 1). There were 215 incident cases of heart failure. Each standard deviation unit increase in the log of plasma total‐tau was associated with a 42% increased risk of incident heart failure (95% confidence interval:1.26‐1.61; p&lt;0.0001) in Model 2 (Table 2). Among individuals with plasma total‐tau values in the top quintile compared to the bottom four quintiles, risk for incident heart failure was increased by 69% (1.26‐2.28; p = 0.0005).ConclusionElevated levels of plasma total‐tau at baseline in this community‐based sample were associated with incidence of congestive heart failure. Circulating tau protein, or possibly byproducts of related neurodegenerative pathways, may represent a shared substrate of protein misfolding, in the brain and the heart, resulting in Alzheimer’s disease and heart failure.

Serum Nf‐L and GFAP are associated with incident dementia and dementia mortality in older adults: The Cardiovascular Health Study

AbstractBackgroundAlthough circulating neurofilament light chain (Nf‐L) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk, their additive association, and their associations with dementia‐specific mortality have not been investigated. Overall, prospective community‐based studies of these biomarkers, particularly those representing individuals beyond their eighth decade, are lacking.MethodWe investigated 1,712 cognitively healthy participants of the Cardiovascular Health Study (1,042 women [61%], 218 Black [13%], median [IQR] baseline age = 77 [74–80] years). Cox regression models were used to test the associations of serum Nf‐L and GFAP, measured using single molecule array technology, with 19‐year incident dementia and dementia‐specific mortality risk. These primary outcomes were complemented by repeated Modified Mini‐Mental State Exam and the Digit Symbol Substitution Test scores which were used in linear mixed models to test the associations of Nf‐L and GFAP with cognitive decline over three years.ResultMore than half of the participants were diagnosed with incident dementia (N = 975) and 183 dementia‐specific deaths occurred during follow‐up. In covariate, and mutual Nf‐L/GFAP adjusted models, each standard deviation unit higher Nf‐L or GFAP associated with a hazard ratio (HR) of 1.14 (95% confidence interval, 1.03–1.26) and 1.12 (1.04–1.21) for incident dementia, and 1.37 (1.11–1.69) and 1.55 (1.31–1.83) for dementia‐specific mortality (Table 1). These associations were graded and additive, with the strongest associations observed when Nf‐L and GFAP levels were simultaneously elevated (Figure 1). Compared to those in the lowest tertiles of both markers, we observed an additive increase in risk among individuals with both Nf‐L and GFAP levels in the highest tertile [HR, 2.06 (1.60‐2.67) for incident dementia and 9.22 (4.48–18.9) for dementia‐specific mortality, Figure 1]. Nf‐L, but not GFAP, independently associated with faster cognitive decline over three years (Table 1).ConclusionCirculating Nf‐L and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Left ventricular myocardial hypertrophy and strain changes in children with hypertrophic cardiomyopathy

Introduction. An assessment of the relationship between the severity of hypertrophy and changes in the myocardial strain at which systolic disfunction is detected in children with hypertrophic cardiomyopathy (HCM) is clearly essential.Aim. To assess the relationship between hypertrophy and the myocardial strain in children with hypertrophic cardiomyopathy (HCM).Materials and methods. 61 patients aged between 7 and 17 years with a primary form of HCM underwent an ultrasound examination of the heart using standard techniques. An assessment of the left ventricular systolic function performed using of-line the two-dimensional (2D) speckle-tracking mode with analysis parameters that included global and segmental longitudinal, circumferential, and radial myocardial strains. The analysis of hypertrophy of myocardial segments carried out taking into account the absolute values of the thickness of the left ventricular myocardium in systole and diastole, depending on age, in terms of standard deviation units in the population (Z-score factor).Results. A decrease in longitudinal strain below the relevant values, an increase in radial strain, and no changes in circular strain were observed when the thickness of the left ventricular myocardium increased over 2.48Z. A further decrease in radial strain was observed when myocardial thickness was over 4.24Z, and circular strain was over 3.16Z. The relationship between myocardial hypertrophy and longitudinal strain had an inverse linear relationship: the lower the strain values, the greater the thickness of the myocardium. With increasing thickness of the myocardium, the radial strain first tended to increase in a compensatory manner, but it decreased when myocardial thickness increased over 4.24Z. The circular strain, as well as longitudinal one, has an inverse linear relationship, but with longer preservation of normal values when myocardial hypertrophy increases.Conclusion. Children with HCM demonstrate various types of relationships between hypertrophy and myocardial strain, which detection is important for the assessment of the left ventricular systolic function to improve the prognosis and therapeutic approach to the disease. A comprehensive approach to the assessment of myocardial strain in children with HCM should include not only a routine identification of global strain, but also assessment of the segmental strain to detect early signs of myocardial dysfunction. Comparison of measures of various types of strain and the thickness of the left ventricular myocardium has a very important diagnostic value for understanding the degree of changes in its kinetics.

Teacher connection and student perspective-taking and their association with school belonging among adolescents in 62 countries

ABSTRACT Addressing worldwide declines in adolescents’ school belonging requires identifying factors to target in reversing this trend. We hypothesized that adolescents with higher levels of teacher connection and perspective-taking would have greater school belonging and that the joint association of both factors with school belonging would be more than additive. We analysed cross-sectional survey data from 15-year-olds in 62 countries (N = 392,096) collected in the 2018 Programme for International Student Assessment. Measures were expressed in standard deviation (SD) units. Based on regression models with both factors plus covariates, school belonging increased 0.12 (95% CI: 0.11, 0.13) units for a 1.00 SD increase in teacher connection and 0.09 units (95% CI: 0.08, 0.10) for a 1.00 SD increase in perspective-taking. The observed (joint) association of both factors with school belonging was 19.0% greater than the expected (additive) association. Efforts to increase teacher connection and perspective-taking could improve school belonging.

Observation of Gamma Rays up to 320 TeV from the Middle-aged TeV Pulsar Wind Nebula HESS J1849−000

Gamma rays from HESS J1849−000, a middle-aged TeV pulsar wind nebula (PWN), are observed by the Tibet air shower array and the muon detector array. The detection significance of gamma rays reaches 4.0σ and 4.4σ levels above 25 TeV and 100 TeV, respectively, in units of the Gaussian standard deviation σ. The energy spectrum measured between 40 TeV < E < 320 TeV for the first time is described with a simple power-law function of . The gamma-ray energy spectrum from the sub-TeV (E < 1 TeV) to sub-PeV (100 TeV < E < 1 PeV) ranges, including the results of previous studies, can be modeled with the leptonic scenario, i.e., inverse Compton scattering by high-energy electrons accelerated by the PWN of PSR J1849−0001. On the other hand, the gamma-ray energy spectrum can also be modeled with the hadronic scenario in which gamma rays are generated from the decay of neutral pions produced by collisions between accelerated cosmic-ray protons and the ambient molecular cloud found in the gamma-ray-emitting region. The cutoff energy of cosmic-ray protons E p,cut is estimated as , suggesting that protons are accelerated up to the PeV energy range. Our study thus proposes that HESS J1849−000 should be further investigated as a new candidate as a Galactic PeV cosmic-ray accelerator, or “PeVatron.”

Change in Alcohol Consumption in Adolescence and Emerging Adulthood: A Meta-Analysis.

Most young people start to drink alcohol in adolescence and increase their consumption until their early 20s. The present study meta-analyzed results of longitudinal studies across the age range of 10 to 25 years. A systematic search in the PsycINFO, PSYNDEX, and Web of Science databases resulted in 513 studies that were included in multilevel meta-analysis. On average, alcohol consumption increased by .21 standard deviation units per year, with the strongest increase at age 12 to 13 years. Regarding cumulative change, drinking peaked around 22 years. Drinking started to decline at age 24, with minor changes being observed in 24- and 25-year-olds. Female participants increased their consumption less than their male peers, but gender differences were very small. Weaker increases in drinking were found in countries with higher minimum legal age of buying alcohol. Passing the minimum legal age of 16 years was associated with a stronger immediate increase in drinking compared with countries with higher minimum legal age, whereas passing higher minimum legal ages had no effect on alcohol consumption. In U.S. samples, smaller increases in drinking were observed in more recent studies. Prevention must start before age 12. Passing a low minimum legal drinking age only seems to have a short-term effect on alcohol consumption.

How to Use Percentiles to Better Understand Standardized Mean Difference (SMD) as a Measure of Effect Size.

The standardized mean difference (SMD) is the difference between the means of a variable, expressed not in its original unit but in the unit of standard deviation (SD). SMDs of 0.2, 0.5, and 0.8 are conventionally considered to be small, medium, and large, respectively. The reader, however, obtains no real world understanding of an SMD from these adjectives. This article suggests a solution: SMDs and their 95% confidence intervals can be better understood if they are converted into percentile scores. The procedure is explained, step by step, with reference to a meta-analysis that found that cholinesterase inhibitors (ChEIs) significantly attenuated delusions and hallucinations in Alzheimer disease and Parkinson disease with SMDs that ranged from -0.08 to -0.14. After conversion of these SMDs to percentile scores, the reader is shown that the average patient in the ChEI treatment arms would have improved by just 3 to 7 percentile places relative to the average patient in the placebo arms. So, whereas the findings were statistically significant, they would perhaps be so small as to be clinically unobservable in the average patient. All that the reader needs to do to convert an SMD into a percentile score is to locate a table that presents area under the normal curve, understand how the table presents what it does, look up the SMD value in the table, and obtain the percentile score from the value in the table. The entire procedure is very easily understood and takes less than a minute, starting from locating the table through an online search to obtaining the percentile score for the SMD.

Post Hoc Analyses of a Randomized Controlled Trial for the Effect of Pharmacist Deprescribing Intervention on the Anticholinergic Burden in Frail Community-Dwelling Older Adults.

Anticholinergic burden is detrimental to cognitive health. Multiple studies found that a high anticholinergic burden is associated with an increased risk for dementia, changes to the brain structure, function, and cognitive decline. We performed a post hoc analysis of a randomized controlled deprescribing trial. We compared the effect of the intervention on baseline anticholinergic burden across the treatment and control groups and the time of recruitment before and after a lockdown due to the COVID pandemic with subgroup analyses by baseline frailty index. Randomized controlled trial. We analyzed data from a de-prescribing trial of older adults (>65years) previously conducted in New Zealand that was focused on reducing the Drug Burden Index (DBI). We used the anticholinergic cognitive burden (ACB) to quantify the impact of the intervention on reducing the anticholinergic burden. Participants not taking anticholinergics at the start of the trial were excluded. The primary outcome for this subgroup analysis was a change in ACB, measured with the ĝHedges statistic describing the difference in standard deviation units of this change between intervention and control. For this analysis, the trial participants were stratified into low, medium, and high frailty and timing into prior- and post-lockdown (public health measures for COVID-19). Among the 295 participants in this analysis, the median (IQR) age was 79 (74, 85), and 67% were women. For the primary outcome ĝHedges=-0.04 (95% CI-0.26 to 0.19) with a-0.23 mean reduction in ACB in the intervention arm and-0.19 in the control arm. Before lockdown ĝHedges=-0.38 (95% CI-0.84 to 0.04) and post-lockdown ĝHedges= 0.07 (95% CI-0.19 to 0.33). The mean change in ACB for each of the frailty strata was as follows: low frailty (-0.02; 95% CI-0.65 to 0.18); medium frailty (0.05; 95% CI-0.28 to 0.38); high frailty (0.08; 95% CI-0.40 to 0.56). The study did not provide evidence for the effect of pharmacist deprescribing intervention on reducing the anticholinergic burden. However, this post hoc analysis examined the impact of COVID on the effectiveness of the intervention, and further research in this area may be warranted.

A South Korean study of age trends in HEXACO-PI-R self-reports

We examined age trends in mean scores on self-report scales of the HEXACO Personality Inventory—Revised (HEXACO-PI-R) in a cross-sectional sample of 147,564 South Korean respondents with ages ranging from 14 to 70 years. The most prominent trends were observed for the Honesty-Humility and Conscientiousness factor scales, where in each case respondents in their 60s averaged about one full standard deviation unit higher than did respondents under 20. Within several factor scales, facet-level scales differed widely in their age trends. The pattern of the Korean age trends was generally similar to that observed in a previous study involving persons mostly from English-speaking countries. This similarity suggests that some of the observed age trends could reflect universal developmental tendencies.

The Establishment of the Cut-off Value of Weight-for-Height for Preschool Children in China and an Empirical Study on the Influence of Overweight and Obesity on Physical Performance.

We aimed to establish the cut-off value of weight-for-height for preschool children in China, and to explore the influence of overweight and obesity on the physical performance of preschool children. Data from 31 provinces in China monitored in 2010 and 2014, the standard deviation unit curves of WFH were established by using GAMLSS (generalized additive model for location, scale, and shape) method preschool children in China, and then the cut-off values of normal weight, overweight and obesity were divided. The research group tested 5 physical performance indicators of 5154 preschool children from April 2018 to June 2019 in Beijing and Zhejiang in China. We then compared physical performance differences between the normal-weight group and the overweight-obesity group. A smooth and effective standard deviation unit curve of WFH was established. The overweight and obesity of Chinese preschool children were at a high level. Being overweight and obese reduced preschool children's relative strength, speed, sensitivity, coordination, and balance ability, but did not reduce preschool children's flexibility. In general, the physical performance of preschool children in the normal weight group was better than that in the overweight and obesity group. It is suggested to use the WFH criteria in this study to evaluate overweight and obesity in Chinese preschool children, and strengthen physical activity and take in energy substances properly of preschool children, to control the spread of overweight and obesity, to improve physical performance level.

Observational and genetic evidence support a relationship between cardiac autonomic function and blood pressure.

It is unclear how cardiac autonomic function, as indicated by heart rate (HR), heart rate variability (HRV), HR increase during exercise, and HR recovery after exercise, is related to blood pressure (BP). We aimed to examine the observational and genetic evidence for a potential causal effect of these HR(V) traits on BP. We performed multivariable adjusted linear regression using Lifelines and UK Biobank cohorts to investigate the relationship between HR(V) traits and BP. Linkage disequilibrium score regression was conducted to examine genetic correlations. We used two-sample Mendelian randomization (2SMR) to examine potential causal relations between HR(V) traits and BP. Observational analyses showed negative associations of all HR(V) traits with BP, except for HR, which was positively associated. Genetic correlations were directionally consistent with the observational associations, but most significant genetic correlations between HR(V) traits and BP were limited to diastolic blood pressure (DBP). 2SMR analyses suggested a potentially causal relationship between HR(V) traits and DBP but not systolic blood pressure (SBP). No reverse effect of BP on HR(V) traits was found. One standard deviation (SD) unit increase in HR was associated with a 1.82 mmHg elevation of DBP. In contrast, one ln(ms) unit increase of the root mean square of the successive differences (RMSSD) and corrected RMSSD (RMSSDc), decreased DBP by 1.79 and 1.83 mmHg, respectively. For HR increase and HR recovery at 50 s, every additional SD increase was associated with a lower DBP by 2.05 and 1.47 mmHg, respectively. Results of secondary analyses with pulse pressure as outcome were inconsistent between observational and 2SMR analyses, as well as between HR(V) traits, and therefore inconclusive. Both observational and genetic evidence show strong associations between indices of cardiac autonomic function and DBP, suggesting that a larger relative contribution of the sympathetic versus the parasympathetic nervous system to cardiac function may cause elevated DBP.

Systemic Inflammation, Endothelial Function, and Risk of Periodontitis in Overweight/Obese Adults.

The network interaction between systemic inflammatory mediators, endothelial cell adhesion function, and adiponectin as mediators of the association between metabolic diseases and periodontitis has not been evaluated. The objective of this study is to assess whether the interaction of baseline serum levels of TNF-α, hs-CRP, ICAM-1, VCAM-1, and adiponectin leads to periodontitis. Five hundred and ninety-seven overweight/obese (overweight: BMI 25 to <30 kg/m2; obese: >30 kg/m2) adults, aged 40-65 years, with complete 3-year follow-up data were included. Generalized structural equation models with negative binomial regression were used to estimate the regression coefficient (β) for the outcome number of teeth with probing pocket depth (PPD) ≥ 4 mm and bleeding on probing (BOP) at 3-year follow-up for a 1 standard deviation unit increase (Δ = +1SD) in each biomarker. After adjusting for multiple covariates, baseline ICAM-1 and VCAM-1 had significant direct effects on increased log-transformed number of teeth with PPD ≥ 4 mm and BOP (β: 0.16; 95% CI: 0.02-0.30; β: 0.15; 95% CI: 0.02-0.30, respectively). Baseline hs-CRP showed a significant indirect effect via ICAM-1 on the log-transformed number of teeth with PPD ≥ 4 mm and BOP (β: 4.84; 95% CI: 0.27-9.42). Thus, elevated serum ICAM-1 and VCAM-1 have a significant direct effect and increased hs-CRP has a significant indirect effect on the predicted level of periodontitis at the 3-year follow-up among overweight/obese Hispanic adults.