Snus use and rejection in the USA

OBJECTIVE: To determine whether snus might become a strategy for reducing the harm associated with cigarette smoking in the USA as appears to be the case in Sweden, we examined receptivity to snus use in two cities with the greatest exposure to the major brands. METHODS: A dual frame, telephone survey and a brief mail survey were conducted in 2011 and 2012 in Indianapolis, Indiana and Dallas/Fort Worth Texas. Over 5000 adults completed surveys. Trial, ever use, current use and reasons for using or quitting snus after trial were measured. RESULTS: Among male smokers, 29.9% had ever tried snus (CI 22.7 to 38.1) and 4.2% were current users (CI 1.6 to 10.7). Among female smokers, 8.5% ever tried snus (CI 4.4 to 15.7) and current use was unknown. Current use was virtually absent among former smokers and never smokers. A major predictor of any level of snus use was current use of conventional smokeless tobacco. Those who tried and gave up snus cited curiosity (41.3%) and the fact that it was available at low or no cost (30%) as reasons for trial; reasons for not continuing included preferring another form of tobacco (75.1%) and disliking the mouth feel (34.6%). Almost all current snus users indicated that they were trying to cut down on cigarettes, but few (3.9%) were using it to quit smoking entirely. CONCLUSIONS: The low rate of adoption of snus suggests that neither the hopes nor the fears surrounding this new product are likely to be realised in the USA with the current marketing patterns

Bifactor analysis of motivation for charity sport event participation

The purpose of this study was to examine the utility of the existing subscales of charity sport events (CSEs) participation motivation by adopting both a second-order modeling and a bifactor modeling approaches. The results with 488 college students revealed that the bifactor model provided a better interpretation of the data compared to second-order model. The five-factor CSE motivation significantly predict the intention to participate in CSEs along with two domain-specific motivations, namely ‘sport and event’ and ‘cause’ while other three domain-specific motivations including ‘philanthropic’, ‘social interaction’, and ‘reference group’ are not statistically significant predictors. The results suggest that the bifactor model is more useful in predicting this group’s participation in charity sport events. © 2015, Springer-Verlag Berlin Heidelberg

A rare mutation in SMAD9 associated with high bone mass identifies the SMAD-dependent BMP signalling pathway as a potential anabolic target for osteoporosis

Novel anabolic drug targets are needed to treat osteoporosis. Having established a large national cohort with unexplained high bone mass (HBM), we aimed to identify a novel monogenic cause of HBM and provide insight into a regulatory pathway potentially amenable to therapeutic intervention. We investigated a pedigree with unexplained HBM in whom previous sequencing had excluded known causes of monogenic HBM. Whole exome sequencing identified a rare (minor allele frequency 0.0023), highly evolutionarily conserved missense mutation in SMAD9 (c.65T>C, p.Leu22Pro) segregating with HBM in this autosomal dominant family. The same mutation was identified in another two unrelated individuals both with HBM. In silico protein modeling predicts the mutation severely disrupts the MH1 DNA-binding domain of SMAD9. Affected individuals have bone mineral density (BMD) Z-scores +3 to +5, mandible enlargement, a broad frame, torus palatinus/mandibularis, pes planus, increased shoe size, and a tendency to sink when swimming. Peripheral quantitative computed tomography (pQCT) measurement demonstrates increased trabecular volumetric BMD and increased cortical thickness conferring greater predicted bone strength; bone turnover markers are low/normal. Notably, fractures and nerve compression are not found. Both genome-wide and gene-based association testing involving estimated BMD measured at the heel in 362,924 white British subjects from the UK Biobank Study showed strong associations with SMAD9 (P-GWAS = 6 x 10(-16); P-GENE = 8 x 10(-17)). Furthermore, we found Smad9 to be highly expressed in both murine cortical bone-derived osteocytes and skeletal elements of zebrafish larvae. Our findings support SMAD9 as a novel HBM gene and a potential novel osteoanabolic target for osteoporosis therapeutics. SMAD9 is thought to inhibit bone morphogenetic protein (BMP)-dependent target gene transcription to reduce osteoblast activity. Thus, we hypothesize SMAD9 c.65T>C is a loss-of-function mutation reducing BMP inhibition. Lowering SMAD9 as a potential novel anabolic mechanism for osteoporosis therapeutics warrants further investigation. (c) 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Whole-genome genotyping of grape using a panel of microsatellite

The use of microsatellite markers in large-scale genetic studies is limited by its low throughput and high cost and labor requirements. Here, we provide a panel of 45 multiplex PCRs for fast and cost-efficient genome-wide fluorescence-based microsatellite analysis in grapevine. The developed multiplex PCRs panel (with up to 15-plex) enables the scoring of 270 loci covering all the grapevine genome (9 to 20 loci/chromosome) using only 45 PCRs and sequencer runs. The 45 multiplex PCRs were validated using a diverse grapevine collection of 207 accessions, selected to represent most of the cultivated Vitis vinifera genetic diversity. Particular attention was paid to quality control throughout the whole process (assay replication, null allele detection, ease of scoring). Genetic diversity summary statistics and features of electrophoretic profiles for each studied marker are provided, as are the genotypes of 25 common cultivars that could be used as references in other studies

Evolution of the Earliest Horses Driven by Climate Change in the Paleocene-Eocene Thermal Maximum

Body size plays a critical role in mammalian ecology and physiology. Previous research has shown that many mammals became smaller during the Paleocene-Eocene Thermal Maximum (PETM), but the timing and magnitude of that change relative to climate change have been unclear. A high-resolution record of continental climate and equid body size change shows a directional size decrease of ~30% over the first ~130,000 years of the PETM, followed by a ~76% increase in the recovery phase of the PETM. These size changes are negatively correlated with temperature inferred from oxygen isotopes in mammal teeth and were probably driven by shifts in temperature and possibly high atmospheric CO2 concentrations. These findings could be important for understanding mammalian evolutionary responses to future global warming