The Future of American Sentencing: A National Roundtable on Blakely

In the wake of the dramatic Supreme Court decision in Blakely v. Washington, Stanford Law School convened an assembly of the most eminent academic and professional sentencing experts in the country to jointly assess the meaning of the decision and its implications for federal and state sentencing reform. The event took place on October 8 and 9, just a few months after Blakely came down and the very week that the Supreme Court heard the arguments in United States v. Booker and United States v. Fanfan, the cases that will test Blakely\u27s application to the Federal Sentencing Guidelines. Thus the Roundtable offered these experts an intellectual breathing space at a crucial point in American criminal law. The event was built around six sessions, with shifting panels of participants doing brief presentations on the subject of the session, and with others then joining in the discussion. We are pleased that FSR is able to publish this version of the proceedings of the event-a condensed and edited transcript of the sessions

Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5(p)15.33 TERT-CLPTM1Ll Region

Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Multiomics in the central Arctic Ocean for benchmarking biodiversity change

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth

Linking Molecular Events to Cellular Responses at Low Dose Exposures

The studies proposed in this project are to define thresholds in cell signaling pathways that are required for cellular transformation and may be targeted by low-dose radiation. Defining thresholds in transformation-related signal transduction pathways that are sensitive to low-dose radiation would be an important advancement in risk assessment and could be used to demonstrate nonlinear relationships between low-dose radiation and cancer

Improving Office-based Physicians\u27 Prevention Practices for Sexually Transmitted Diseases

Objective: To determine whether office-based interventions increase primary care physicians\u27 risk assessment of and counseling practices for patients regarding sexually transmitted diseases and the human immunodeficiency virus (HIV). Design: Randomized controlled clinical trial. Setting: Washington, D.C., Metropolitan Statistical Area. Study Participants: Office-based primary care physicians (family or general practice, internal medicine, and obstetrics-gynecology). Intervention: Mailed educational materials alone or coupled with a simulated patient instructor office visit. Measurements: Self-reported and observed frequency of assessing and counseling patients regarding their risk factors for sexually transmitted diseases and HIV infection. Participants were interviewed by telephone before and after the intervention by simulated patient evaluators in blinded office visits. Results: 89% of physicians who received both educational materials and a simulated patient instructor visit reported that they reviewed the educational materials compared with 53% of those who only received the educational materials (P≤ 0.001). Physicians in the combined intervention group had higher self-reported and observed rates for several risk assessment questions and counseling recommendations than did physicians in the control group or the group that only received educational materials. Seventy-three percent of physicians of the combined intervention group reported an increase in counseling patients about reducing risky sexual behavior compared with 53% of the group receiving only educational materials and 42% of the control group (P≤ 0.001). Conclusions: Mailed educational materials combined with an office visit by a simulated patient instructor for role-play and feedback on clinical performance increased the frequency of office-based physicians\u27 risk assessment and risk reduction counseling of patients for sexually transmitted diseases and HIV infection

Improving Office-based Physicians\u27 Prevention Practices for Sexually Transmitted Diseases

Objective: To determine whether office-based interventions increase primary care physicians\u27 risk assessment of and counseling practices for patients regarding sexually transmitted diseases and the human immunodeficiency virus (HIV). Design: Randomized controlled clinical trial. Setting: Washington, D.C., Metropolitan Statistical Area. Study Participants: Office-based primary care physicians (family or general practice, internal medicine, and obstetrics-gynecology). Intervention: Mailed educational materials alone or coupled with a simulated patient instructor office visit. Measurements: Self-reported and observed frequency of assessing and counseling patients regarding their risk factors for sexually transmitted diseases and HIV infection. Participants were interviewed by telephone before and after the intervention by simulated patient evaluators in blinded office visits. Results: 89% of physicians who received both educational materials and a simulated patient instructor visit reported that they reviewed the educational materials compared with 53% of those who only received the educational materials (P≤ 0.001). Physicians in the combined intervention group had higher self-reported and observed rates for several risk assessment questions and counseling recommendations than did physicians in the control group or the group that only received educational materials. Seventy-three percent of physicians of the combined intervention group reported an increase in counseling patients about reducing risky sexual behavior compared with 53% of the group receiving only educational materials and 42% of the control group (P≤ 0.001). Conclusions: Mailed educational materials combined with an office visit by a simulated patient instructor for role-play and feedback on clinical performance increased the frequency of office-based physicians\u27 risk assessment and risk reduction counseling of patients for sexually transmitted diseases and HIV infection