Investing in Prevention or Paying for Recovery - Attitudes to Cyber Risk

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Broadly speaking an individual can invest time and effort to avoid becoming victim to a cyber attack and/or they can invest resource in recovering from any attack. We introduce a new game called the pre-vention and recovery game to study this trade-off. We report results from the experimental lab that allow us to categorize different approaches to risk taking. We show that many individuals appear relatively risk loving in that they invest in recovery rather than prevention. We find little difference in behavior between a gain and loss framing

The Rayed Head and Stepped Platform: A Core Symbol of the Southern Andean Iconographic Series

This paper will explore various manifestations of the Rayed Head motif that is found on textiles produced by the Nasca, Sihuas, and Pucara cultures during the Early Intermediate Period (200 BCE – 600 CE), in the southern Andean region of South America. The Brooklyn Museum’s famous Nasca mangle, also known as “The Paracas Textile,” features repeating images of the Rayed Head motif on its interior cotton panel. Sihuas mantles also display distinctive manifestations of the motif in the form of a large rectangular head with highly stylized features and surrounded by radiating appendages. The late textile scholar and archaeologist Joerg Haeberli has pointed out many similarities between Sihuas and Nasca textiles such as their weaving techniques and iconography (including the Rayed Head), and has proposed that the valleys of Arequipa and the south coast were linked during the late Early Horizon and Early Intermediate Period, perhaps due to dispersed Nasca enclaves in Arequipa. Utilizing textiles in the Brooklyn Museum and other public and private collections, the author will further explore this regional relationship as well as a similar iconographic correspondence with the Rayed Head motif found on Pucara-style objects associated with the Yaya-Mama (Father-Mother) religious tradition in the Lake Titicaca of Peru and Bolivia

Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study

BackgroundAlcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.Methods and findingsUsing large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10-2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14-2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38-4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.ConclusionsEvaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk

Alcohol and aging: Next‐generation epigenetic clocks predict biological age acceleration in individuals with alcohol use disorder

Background: Chronic heavy alcohol use is a major risk factor for premature aging and age‐related diseases. DNA methylation (DNAm)‐based epigenetic clocks are novel tools for predicting biological age. However, the newest configurations, causality‐enriched epigenetic clocks, have not been assessed in the context of alcohol consumption and alcohol use disorder (AUD). Methods: Epigenetic aging was evaluated in a sample of 615 individuals (372 AUD patients and 243 healthy controls) by applying the GrimAge Version 1 (V1) and Version 2 (V2) clocks alongside three causality‐enriched clocks (CausAge, DamAge, and AdaptAge). A linear model controlling for AUD diagnosis, sex, race, BMI, smoking status, and five blood cell types was leveraged to test associations between alcohol‐related metrics and age‐adjusted epigenetic clocks. Results: GrimAge V1 and V2 maintained significant associations with AUD and drinking behavior measures within the total sample and both the young (<40 years old) and old (≥40 years old) subgroups. Generally, GrimAge V2 slightly outperformed GrimAge V1, while none of the causality‐enriched epigenetic clocks demonstrated significant associations with AUD. However, in the young subgroup, DamAge had a significant association with the total number of drinks. Across the total sample and age subgroups, with liver function enzymes, GrimAge V2 consistently sustained stronger associations compared with GrimAge V1. Among fourth‐generation clocks, DamAge exhibited significant associations with gamma‐glutamyl transferase (GGT) and aspartate aminotransferase in the total sample and young subgroup; CausAge displayed a significant association with GGT in the total sample. Examining clinical biomarkers, GrimAge V2 showed improved associations with C‐reactive protein compared to GrimAge V1 in the total sample and age subgroups. Conclusions: Overall, we observed moderately improved performance of GrimAge V2 compared with GrimAge V1 with the majority of the parameters tested. The causality‐enriched epigenetic clocks lacked significant associations but demonstrate the complexities of aging and inspire further research of AUD and drinking dynamics

Genetically modeled GLP1R and GIPR agonism reduce binge drinking and alcohol-associated phenotypes: a multi-ancestry drug-target Mendelian randomization study

Pharmacological modulation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) through dual GIP/GLP-1 receptor agonists, commonly used for diabetes and obesity, shows promise in reducing alcohol consumption. We applied drug-target Mendelian randomization (MR) using genetic variation at these loci to assess their long-term effects on problematic alcohol use (PAU), binge drinking, alcohol misuse classifications, liver health, and other substance use behaviors. Genetic proxies for lowered BMI, modeling the appetite-suppressing and weight-reducing effects of variants in both the GIPR and GLP1R loci (“GIPR/GLP1R”), were linked with reduced binge drinking in the primary (β = −0.44, 95% CI [−0.72, −0.15], P = 2.42 × 10−3) and replication data (β = −0.13, [−0.22, −0.04], P = 0.0058). HbA1c lowering via GIPR/GLP1R variants was associated with reduced risk of heavy drinking with psychiatric comorbidities versus low-risk drinking (odds ratio [OR] = 0.62, [0.45, 0.85], P = 0.0031), with replication in independent HbA1c data (OR = 0.71, [0.60, 0.84], P = 5.22 × 10−5) and directional consistency with reduced PAU. Analysis of individual loci indicated that both GIPR and GLP1R were protective against heavy drinking, underscoring the importance of both targets. While estimates for other substance use disorders (tobacco, cannabis, opioid) were consistently null, food preference analyses revealed that BMI lowering via GIPR/GLP1R reduced fatty food liking (β = −1.58, [−2.01, −1.14], P = 1.62 × 10−12) and increased vegetarian food liking (β = 2.08, [1.17, 2.99], P = 8.22 × 10−6), implicating metabolic and appetite regulation pathways for the alcohol consumption findings. For liver health, HbA1c lowering via GIPR/GLP1R was associated with reduced NAFLD (β = −0.34, [−0.50, −0.18], P = 2.74 × 10−5) and lower ALT levels (β = −0.26, [−0.38, −0.15], P = 8.39 × 10−6), with replication supporting these findings. Consistency across multiple MR methods and colocalization analyses strengthened causal inference. Mediation analysis suggested reductions in hazardous alcohol consumption partially explain the cardioprotective effects of these agonists. Multi-ancestry analyses supported directionally aligned relationships in non-European cohorts. These findings support further clinical exploration of GLP1R, GIPR, and dual agonists in addiction medicine