Evaluating the Outcomes of the Menthol Cigarette Ban in England by Comparing Menthol Cigarette Smoking Among Youth in England, Canada, and the US, 2018-2020

Importance: Menthol cigarettes were prohibited in England in May 2020 and nationally in Canada in October 2017 but remain permitted in the US. Evidence on the outcomes of menthol cigarette bans among youth outside of Canada, and the characteristics of youth smokers, is lacking. Objectives: To evaluate the outcomes of menthol cigarette bans on youth menthol cigarette smoking and to characterize youth menthol cigarette smokers in terms of demographics and cigarette consumption and dependence. Design, Setting, and Participants: This survey study uses data from online repeat cross-sectional International Tobacco Control Youth Tobacco and Vaping Surveys conducted in 2018, 2019, February 2020, and August 2020. Participants included past 30-day smokers aged 16 to 19 years. Data analysis was performed from March 2021 to January 2022. Main Outcomes and Measures: Usually smoke a brand of cigarettes that was menthol, including capsule. Exposures: Menthol cigarette ban, comparing 3 countries over time: Canada, where a ban already existed, England, where a ban was implemented during the study, and the US, where no national ban was present. Age, sex, race, and consumption and dependence were also examined by menthol smoking in each country, and in England before vs after the ban. Results: The analytical sample comprised 7067 participants aged 16 to 19 years, of whom 4129 were female and 5019 were White. In England, the weighted percentage of youth smokers who reported smoking a menthol or capsule cigarette brand was stable in the 3 survey waves before the menthol ban (2018 to February 2020, 9.4% vs 12.1%; adjusted odds ratio [AOR], 1.03; 95% CI, 0.99-1.06; P = .15) but decreased to 3.0% after the ban (February 2020 vs August 2020, AOR, 1.07; 95% CI, 1.04-1.10; P 5 vs 1, AOR, 1.10; 95% CI, 1.03-1.18; P = .007), or had urges to smoke every or most days (AOR, 1.08; 95% CI, 1.02-1.14; P = .006); and among smokers in Canada who perceived themselves as addicted to cigarettes (AOR, 1.02; 95% CI, 1.00-1.03; P = .01). Conclusions and Relevance: In this survey study, the proportion of youth smokers who smoke menthol (including capsule) cigarettes decreased substantially after the menthol ban in England. This association was consistent across all demographic groups. Perceived addiction among menthol smokers was also lower where menthol cigarettes were banned

Characterization and comparison of recombinant full-length ursine and human sex hormone-binding globulin

Sex hormone‐binding globulin (SHBG) regulates the bioavailability of sex steroid hormones in the blood. Levels of SHBG increase markedly in brown bears (Ursus arctos) during hibernation, suggesting that a key regulatory role of this protein is to quench sex steroid bioavailability in hibernation physiology. To enable characterization of ursine SHBG and a cross species comparison, we established an insect cell‐based expression system for recombinant full‐length ursine and human SHBG. Compared with human SHBG, we observed markedly lower secretion levels of ursine SHBG, resulting in a 10‐fold difference in purified protein yield. Both human and ursine recombinant SHBG appeared as dimeric proteins in solution, with a single unfolding temperature of ~ 58 °C. The thermal stability of ursine and human SHBG increased 5.4 and 9.5 °C, respectively, in the presence of dihydrotestosterone (DHT), suggesting a difference in affinity. The dissociation constants for [(3)H]DHT were determined to 0.21 ± 0.04 nm for human and 1.32 ± 0.10 nm for ursine SHBG, confirming a lower affinity of ursine SHBG. A similarly reduced affinity, determined from competitive steroid binding, was observed for most steroids. Overall, we found that ursine SHBG had similar characteristics to human SHBG, specifically, being a homodimeric glycoprotein capable of binding steroids with high affinity. Therefore, ursine SHBG likely has similar biological functions to those known for human SHBG. The determined properties of ursine SHBG will contribute to elucidating its potential regulatory role in hibernation physiology

Sex hormone-binding globulin regulation of androgen bioactivity in vivo : validation of the free hormone hypothesis

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a liganddependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology

Modeling the impact of melt on seismic properties during mountain building

Initiation of partial melting in the mid/lower crust causes a decrease in P-wave and S-wave velocities; recent studies imply that the relationship between these velocities and melt is not simple. We have developed a modelling approach to assess the combined impact of various melt and solid phase properties on seismic velocities and anisotropy. The modelling is based on crystallographic preferred orientation (CPO) data measured from migmatite samples, allowing quantification of the variation of seismic velocities with varying melt volumes, shapes, orientations, and matrix anisotropy. The results show non-linear behaviour of seismic properties as a result of the interaction of all of these physical properties, which in turn depend on lithology, stress regime, strain rate, pre-existing rock fabrics, and pressure-temperature conditions. This non-linear behaviour is evident when applied to a suite of samples from a traverse across a migmatitic shear zone in the Seiland Igneous Province, Northern Norway. Critically, changes in solid phase composition and CPO, and melt shape and orientation with respect to the wave propagation direction can result in huge variations in the same seismic property even if the melt fraction remains the same. A comparison with surface wave interpretations from tectonically active regions highlights the issues in current models used to predict melt percentages or partially molten regions. Interpretation of seismic data to infer melt percentages or extent of melting should, therefore, always be underpinned by robust modelling of the underlying geological parameters combined with examination of multiple seismic properties in order to reduce uncertainty of the interpretation

Genetic Determinants of Serum Testosterone Concentrations in Men

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation

A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine

<p>Abstract</p> <p>Background</p> <p>In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized medicine, in which an individual's health is optimized through the use of all available patient data, including data on the individual's genome and its downstream products. Genomic and personalized medicine could transform healthcare systems and catalyze significant reductions in morbidity, mortality, and overall healthcare costs.</p> <p>Discussion</p> <p>Critical to the achievement of more efficient and effective healthcare enabled by genomics is the establishment of a robust, nationwide clinical decision support infrastructure that assists clinicians in their use of genomic assays to guide disease prevention, diagnosis, and therapy. Requisite components of this infrastructure include the standardized representation of genomic and non-genomic patient data across health information systems; centrally managed repositories of computer-processable medical knowledge; and standardized approaches for applying these knowledge resources against patient data to generate and deliver patient-specific care recommendations. Here, we provide recommendations for establishing a national decision support infrastructure for genomic and personalized medicine that fulfills these needs, leverages existing resources, and is aligned with the <it>Roadmap for National Action on Clinical Decision Support </it>commissioned by the U.S. Office of the National Coordinator for Health Information Technology. Critical to the establishment of this infrastructure will be strong leadership and substantial funding from the federal government.</p> <p>Summary</p> <p>A national clinical decision support infrastructure will be required for reaping the full benefits of genomic and personalized medicine. Essential components of this infrastructure include standards for data representation; centrally managed knowledge repositories; and standardized approaches for leveraging these knowledge repositories to generate patient-specific care recommendations at the point of care.</p

Perspectives on Risk Perceptions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72341/1/j.1539-6924.1981.tb01409.x.pd

Exploring the interpersonal-, organization-, and system-level factors that influence the implementation and use of an innovation-synoptic reporting-in cancer care

<p>Abstract</p> <p>Background</p> <p>The dominant method of reporting findings from diagnostic and surgical procedures is the narrative report. In cancer care, this report inconsistently provides the information required to understand the cancer and make informed patient care decisions. Another method of reporting, the synoptic report, captures specific data items in a structured manner and contains only items critical for patient care. Research demonstrates that synoptic reports vastly improve the quality of reporting. However, synoptic reporting represents a complex innovation in cancer care, with implementation and use requiring fundamental shifts in physician behaviour and practice, and support from the organization and larger system. The objective of this study is to examine the key interpersonal, organizational, and system-level factors that influence the implementation and use of synoptic reporting in cancer care.</p> <p>Methods</p> <p>This study involves three initiatives in Nova Scotia, Canada, that have implemented synoptic reporting within their departments/programs. Case study methodology will be used to study these initiatives (the cases) in-depth, explore which factors were barriers or facilitators of implementation and use, examine relationships amongst factors, and uncover which factors appear to be similar and distinct across cases. The cases were selected as they converge and differ with respect to factors that are likely to influence the implementation and use of an innovation in practice. Data will be collected through in-depth interviews, document analysis, observation of training sessions, and examination/use of the synoptic reporting tools. An audit will be performed to determine/quantify use. Analysis will involve production of a case record/history for each case, in-depth analysis of each case, and cross-case analysis, where findings will be compared and contrasted across cases to develop theoretically informed, generalisable knowledge that can be applied to other settings/contexts. Ethical approval was granted for this study.</p> <p>Discussion</p> <p>This study will contribute to our knowledge base on the multi-level factors, and the relationships amongst factors in specific contexts, that influence implementation and use of innovations such as synoptic reporting in healthcare. Such knowledge is critical to improving our understanding of implementation processes in clinical settings, and to helping researchers, clinicians, and managers/administrators develop and implement ways to more effectively integrate innovations into routine clinical care.</p

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action