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Introduction About 80% of the 1.1 billion people who smoke tobacco worldwide reside in low- and middle-income countries. Evidence-based approaches to promote cessation include brief advice from health professionals and referrals through quitlines. This study assesses cessation behaviors and the use of cessation services in the past 12 months among current tobacco smokers in 31 countries who attempted to quit. Methods Data came from the Global Adult Tobacco Survey, a household-based survey of non-institutionalized adults aged ≥15 years. Surveys were conducted in 31 countries during 2008–2018; sample sizes ranged from 4,250 (Malaysia) to 74,037 (India), and response rates ranged from 64.4% (Ukraine) to 98.5% (Qatar). In 2019, data from the 31 countries were assessed in June 2019, and indicators included self-reported current (daily or less than daily) tobacco smoking, past-year quit attempts, and cessation methods used in the past 12 months. Results Current tobacco smoking prevalence ranged from 3.7% (Ethiopia) to 38.2% (Greece). Overall, an estimated 176.8 million adults from the 31 countries made a quit attempt in the past 12 months, with country-level prevalence ranging from 16.4% (Greece) to 54.7% (Botswana). Most individuals who made a quit attempt did so without assistance (median=74.4%). Other methods were less prevalent, including quitlines (median=0.2%) and counseling (median=7.2%). Conclusions In the assessed countries, the majority of those who currently smoked tobacco and made a quit attempt did so without assistance; very few reported using quitlines, partly because of the lack of quitlines in some countries. In resource-limited settings, quitlines can play a greater role in helping people quit smoking as part of a comprehensive approach.

Summary Background Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. Methods Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. Findings 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. Interpretation Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. Funding US Centers for Disease Control and Prevention.

Purpose Using cross-sectional data, we measured the association between electronic cigarette (e-cigarette) use and subsequent initiation and sustained use of cigarettes among U.S. youth. Methods Data were pooled from the 2015–2017 National Youth Tobacco Survey, a school-based survey of U.S. students in grades 6–12. Questions on current age and age of first use of different tobacco products (cigarettes, e-cigarettes, cigars, and smokeless tobacco) were used to ascertain the temporal sequence of tobacco product use. The pooled study population was 52,579 youth who 5 years before the survey had never smoked cigarettes. E-cigarette users were defined as those who used e-cigarettes before or without ever smoking cigarettes. Cigarette smoking was assessed with the following measures: ever smoking a cigarette at any time within the past 5 years and sustained smoking (smoked ≥1 year ago and within past 30 days). Adjusted odds ratios (AORs) were calculated, controlling for other tobacco product use and sociodemographics. Results Among never cigarette smokers as of 5 years before the survey, 17.4% used e-cigarettes, and 15.6% first smoked within the past 5 years. Compared with those who did not use e-cigarettes, those who used e-cigarettes had higher odds of ever smoking cigarettes within the past 5 years (AOR = 2.73) and had higher odds of sustained smoking (AOR = 1.55; all p Conclusions E-cigarette use is associated with subsequent initiation and sustained use of cigarettes among youth. Efforts are warranted to reduce youth use of all tobacco products, including e-cigarettes.

Introduction Considerable declines in cigarette smoking have occurred in the U.S. over the past half century. Yet emerging tobacco products, including e-cigarettes, have increased in popularity among U.S. youth and adults in recent years. Nicotine content is an important factor in weighing the potential benefits and risks of e-cigarettes on individual and population level health. This study examined how nicotine concentrations of e-cigarette products sold have changed from 2013 to 2018. Methods E-cigarette sales data aggregated in 4-week periods from March 2, 2013 to September 8, 2018 (66 months total) from convenience store and mass market channels were obtained from Nielsen. Internet and vape shop sales were not available. Internet searches were used to supplement information for nicotine concentration and flavor. Products were categorized by nicotine concentration, flavor, type (disposable or rechargeable), and brand. Dollar sales, unit sales, and average nicotine concentration were assessed. Results During 2013–2018, the average nicotine concentration in e-cigarettes sold increased overall, for all flavor categories, and for rechargeable e-cigarettes. The proportion of total dollar sales comprised of higher nicotine concentration e-cigarettes (>4% mg/mL) increased from 12.3% to 74.7% during 2013–2018, with a similar increase in unit share. Zero-nicotine products accounted for less than 1% of dollar market share across all years analyzed. Conclusions E-cigarettes with higher nicotine concentrations comprise a substantial and increasing portion of U.S. e-cigarette sales. Higher nicotine concentrations may influence patterns of e-cigarette use, including harms from e-cigarette initiation among youth and potential health benefits for adult smokers switching completely to e-cigarettes.

Introduction Workplace tobacco control interventions reduce smoking and secondhand smoke exposure among U.S. workers. Data on smoke-free workplace policy coverage and cessation programs by industry and occupation are limited. This study assessed smoke-free workplace policies and employer-offered cessation programs among U.S. workers, by industry and occupation. Methods Data from the 2014–2015 Tobacco Use Supplement to the Current Population Survey, a random sample of the civilian, non-institutionalized population, were analyzed in 2018. Self-reported smoke-free policy coverage and employer-offered cessation programs were assessed among working adults aged ≥18 years, overall and by occupation and industry. Respondents were considered to have a 100% smoke-free policy if they indicated smoking was not permitted in any indoor areas of their workplace, and to have a cessation program if their employer offered any stop-smoking program within the past year. Results Overall, 80.3% of indoor workers reported having smoke-free policies at their workplace and 27.2% had cessation programs. Smoke-free policy coverage was highest among workers in the education services (90.6%) industry and lowest among workers in agriculture, forestry, fishing, and hunting industry (64.1%). Employer-offered cessation programs were significantly higher among workers reporting 100% smoke-free workplace policies (30.9%) than those with partial/no policies (23.3%) and were significantly higher among indoor workers (29.2%) than outdoor workers (15.0%). Conclusions Among U.S. workers, 100% smoke-free policy and cessation program coverage varies by industry and occupation. Lower smoke-free policy coverage and higher tobacco use in certain industry and occupation groups suggests opportunities for workplace tobacco control interventions to reduce tobacco use and secondhand smoke exposure.

Neonatal intensive care for infants born at 22-24 weeks has become more prevalent in the past three decades, but outcomes remain highly variable between centers, in part due to different approaches in management. With this increased frequency of intervention, there has been concern for a concurrent increase in costs of care for survivors. This article reviews the direct medical, direct non-medical, and indirect costs of care for periviable infants and their families as well as the current limitations of published data. In addition, we highlight the cost-effectiveness of neonatal intensive care and various therapies offered to extremely preterm infants while also considering the ethical dilemmas inherently tied to periviable decision-making. Strategies to improve the gaps in knowledge on the economic impact of the smallest infants are discussed.

Most U.S. adults have voluntary rules prohibiting the use of smoked tobacco products in their homes and vehicles. However, the prevalence of similar rules for electronic vapor products (EVPs) is uncertain. This study assessed the prevalence and correlates of rules prohibiting EVP use inside homes and vehicles. Data from a 2017 Internet-based panel survey of U.S. adults aged ≥18 years (n=4,107) were analyzed. For homes and vehicles, prevalence of reporting that EVP use was not allowed, partially allowed, fully allowed, or unknown was assessed overall and by covariates. Correlates of prohibiting EVP use was assessed by multivariable logistic regression. In homes, 58.6% of adults did not allow EVP use, 7.7% partially allowed use, 10.1% fully allowed use, and 23.6% were unsure of the rules. In vehicles, 63.8% of respondents did not allow EVP use, 6.0% partially allowed use, 8.9% fully allowed use, and 21.4% were unsure of the rules. Following multivariable adjustment, prohibiting EVP use inside homes and vehicles was more likely among respondents with higher income and education, and with a child aged

Purpose We aimed to describe U.S. youth harm perceptions of intermittent tobacco use. Methods Using data from the 2016 National Youth Tobacco Survey of U.S. students (grades 6–12; N = 20,675), we examined prevalence and correlates of all respondents' perceived harm of using four different tobacco products on "some days but not every day." Associations between current (past 30-day) use and harm perceptions were assessed using multivariable regression. Results Perceiving that intermittent use causes "no" or "little" harm was 9.7% for cigarettes, 12.0% for smokeless tobacco, 18.7% for hookah, and 37.5% for e-cigarettes. Compared with those who reported "a lot" of harm, youth with lower harm perceptions were more likely to report current use. Conclusions One in ten youth perceived intermittent cigarette smoking as causing "little" or "no" harm; this perception was higher among current users. Efforts to educate youth about the risks of even intermittent tobacco product use could reduce misperceptions of harm.

Evidence suggests exposure of nicotine-containing e-cigarette aerosol to nonusers leads to systemic absorption of nicotine. However, no studies have examined acute secondhand exposures that occur in public settings. Here, we measured the serum, saliva and urine of nonusers pre- and post-exposure to nicotine via e-cigarette aerosol. Secondarily, we recorded factors affecting the exposure. Six nonusers of nicotine-containing products were exposed to secondhand aerosol from ad libitum e-cigarette use by three e-cigarette users for 2 h during two separate sessions (disposables, tank-style). Pre-exposure (baseline) and post-exposure peak levels (Cmax) of cotinine were measured in nonusers’ serum, saliva, and urine over a 6-hour follow-up, plus a saliva sample the following morning. We also measured solution consumption, nicotine concentration, and pH, along with use behavior. Baseline cotinine levels were higher than typical for the US population (median serum session one = 0.089 ng/ml; session two = 0.052 ng/ml). Systemic absorption of nicotine occurred in nonusers with baselines indicative of no/low tobacco exposure, but not in nonusers with elevated baselines. Median changes in cotinine for disposable exposure were 0.007 ng/ml serum, 0.033 ng/ml saliva, and 0.316 ng/mg creatinine in urine. For tank-style exposure they were 0.041 ng/ml serum, 0.060 ng/ml saliva, and 0.948 ng/mg creatinine in urine. Finally, we measured substantial differences in solution nicotine concentrations, pH, use behavior and consumption. Our data show that although exposures may vary considerably, nonusers can systemically absorb nicotine following acute exposure to secondhand e-cigarette aerosol. This can particularly affect sensitive subpopulations, such as children and women of reproductive age.

The purpose of this study was to use individual-level data to examine the relationship between e-cigarette minimum legal sale age (MLSA) laws and cigarette smoking among U.S. adolescents, adjusting for e-cigarette use.In 2016 and 2017, we regressed (logistic) current (past 30-day) cigarette smoking (from 2009-2014 National Youth Tobacco Surveys [NYTS]) on lagged (laws enacted each year counted for the following year) and unlagged (laws enacted January-June counted for that year) state e-cigarette MLSA laws prohibiting sales to youth aged18 or19 years (depending on the state). Models were adjusted for year and individual- (e-cigarette and other tobacco use, sex, race/ethnicity, and age) and state-level (smoke-free laws, cigarette taxes, medical marijuana legalization, income, and unemployment) covariates.Cigarette smoking was not significantly associated with lagged MLSA laws after adjusting for year (odds ratio [OR] = .87, 95% confidence interval [CI]: .73-1.03; p = .10) and covariates (OR = .85, .69-1.03; p = .10). Unlagged laws were significantly and negatively associated with cigarette smoking (OR = .84, .71-.98, p = .02), but not after adjusting for covariates (OR = .84, .70-1.01, p = .07). E-cigarette and other tobacco use, sex, race/ethnicity, age, and smoke-free laws were associated with cigarette smoking (p .05). Results unadjusted for e-cigarette use and other tobacco use yielded a significant negative association between e-cigarette MLSA laws and cigarette smoking (lagged: OR = .78, .64-.93, p = .01; unlagged: OR = .80, .68-.95, p = .01).After adjusting for covariates, state e-cigarette MLSA laws did not affect youth cigarette smoking. Unadjusted for e-cigarette and other tobacco use, these laws were associated with lower cigarette smoking.

The salinity measured by SBE 41CP and SBE 61 conductivity-temperature-depth (CTD) sensors on deep floats was evaluated by comparison with shipboard CTD casts at deployment, after temperature and pressure were verified as unlikely to be biased. Salinity biases with a negative pressure dependency, expressed as ΔS = ΔSoffset + ap × pressure and ap

Introduction Cigarette smoking continues to be the leading cause of preventable disease and death in the U.S. Smoking also carries an economic burden, including smoking-attributable healthcare spending. This study assessed smoking-attributable fractions in healthcare spending between 2010 and 2014, overall and by insurance type (Medicaid, Medicare, private, out-of-pocket, other federal, other) and by medical service (inpatient, non-inpatient, prescriptions). Methods Data were obtained from the 2010–2014 Medical Expenditure Panel Survey linked to the 2008–2013 National Health Interview Survey. The final sample (n = 49,540) was restricted to non-pregnant adults aged 18 years or older. Estimates from two-part models (multivariable logistic regression and generalized linear models) and data from 2014 national health expenditures were combined to estimate the share of and total (in 2014 dollars) annual healthcare spending attributable to cigarette smoking among U.S. adults. All models controlled for socio-demographic characteristics, health-related behaviors, and attitudes. Results During 2010–2014, an estimated 11.7% (95% CI = 11.6%, 11.8%) of U.S. annual healthcare spending could be attributed to adult cigarette smoking, translating to annual healthcare spending of more than $225 billion dollars based on total personal healthcare expenditures reported in 2014. More than 50% of this smoking-attributable spending was funded by Medicare or Medicaid. For Medicaid, the estimated healthcare spending attributable fraction increased more than 30% between 2010 and 2014. Conclusions Cigarette smoking exacts a substantial economic burden in the U.S. Continuing efforts to implement proven population-based interventions have been shown to reduce the health and economic burden of cigarette smoking nationally.

Approximately 70% of current (past 30-day) adult marijuana users are current tobacco users, which may complicate tobacco cessation. We assessed prevalence and trends in tobacco cessation among adult ever tobacco users, by marijuana use status.Data came from the National Survey on Drug Use and Health, a cross-sectional, nationally representative, household survey of U.S. civilians. Analyses included current, former, and never marijuana users aged≥18 reporting ever tobacco use (cigarette, cigar, chew/snuff). We computed weighted estimates (2013-2014) of current tobacco use, recent tobacco cessation (quit 30days to 12months), and sustained tobacco cessation (quit12months) and adjusted trends in tobacco use and cessation (2005-2014) by marijuana use status. We also assessed the association between marijuana and tobacco use status.In 2013-2014, among current adult marijuana users reporting ever tobacco use, 69.1% were current tobacco users (vs. 38.5% of former marijuana users, p0.0001, and 28.2% of never marijuana users, p0.0001); 9.1% reported recent tobacco cessation (vs. 8.4% of former marijuana users, p0.01, and 6.3% of never marijuana users, p0.001), and 21.8% reported sustained tobacco cessation (vs. 53.1% of former marijuana users, p0.01, and 65.5% of never marijuana users, p0.0001). Between 2005 and 2014, current tobacco use declined and sustained tobacco cessation increased among all marijuana use groups.Current marijuana users who ever used tobacco had double the prevalence (vs. never-marijuana users) of current tobacco use, and significantly lower sustained abstinence. Interventions addressing tobacco cessation in the context of use of marijuana and other substances may be warranted.

The use of Search and Rescue (SAR) drift forecasting in an operational capacity is demonstrated through two SAR case studies, each predicting the drift of a panga skiff for 120 h (Case 1) and 72 h (Case 2). The leeway characteristics of panga skiffs were previously unknown, until a leeway field study was undertaken in mid-2012 to empirically determine the influence of wind and waves on their drift. As part of the two case studies described herein, four ocean models were used as environmental forcing for a stochastic particle trajectory model, to forecast the drift and resulting search areas for the panga skiffs. Each of the four ocean models were tested individually, and then combined into a consensus forecast to ascertain which ocean model was the most accurate in terms of distance error of modelled positions compared to actual panga skiff locations. Additionally, a hit analysis was undertaken to determine whether the panga skiff was located within the forecast search areas for each ocean model, and for consensus search areas. Finally, an assessment of the search area sizes was carried out to assess the single ocean model forecast search area sizes, and how they compared with the consensus search area size. In both of the case studies, all four ocean model forecast search areas contained the panga skiff at the time intervals tested, indicating a 100% hit rate and general consensus between the ocean models. The consensus search area, where all four ocean models overlapped, was approximately one third the size of the average single model search area. This demonstrates that the consensus search areas provide a more efficient search area compared to individual ocean model search area forecasts.

Introduction In recent years, self-reported cigarette smoking has declined among youth and adults, while electronic cigarette (e-cigarette) use has increased. However, sales trends for these products are less certain. This study assessed national and state patterns of U.S. cigarette and e-cigarette unit sales. Methods Trends in cigarette and e-cigarette unit sales were analyzed using retail scanner data from September 25, 2011 through January 9, 2016 for: (1) convenience stores; and (2) all other outlets combined, including supermarkets, mass merchandisers, drug, dollar, and club stores, and military commissaries (online, tobacco-only, and “vape“ shops were not available). Data by store type were available for the total contiguous U.S. and 29 states; combined data were available for the remaining states, except Alaska, Hawaii, and DC. Results During 2011–2015, cigarette sales exhibited a small, significant decrease; however, positive year-over-year growth occurred in convenience stores throughout most of 2015. E-cigarette unit sales significantly increased during 2011–2015, but year-over-year growth slowed and was occasionally negative. Cigarette unit sales exceeded e-cigarettes by 64:1 during the last 4-week period. During 2014–2015, cigarette sales increases occurred in 15 of 48 assessed states; e-cigarette sales increased in 18 states. Conclusions Despite overall declines during 2011–2015, cigarette sales in 2015 grew for the first time in a decade. E-cigarette sales growth was positive, but slowed over the study period in assessed stores. Cigarette sales continued to exceed e-cigarette sales, reinforcing the importance of efforts to reduce the appeal and accessibility of cigarettes and other combusted tobacco products.

While the high costs of neonatal intensive care have been a topic of increasing study, the financial impact on families have been less frequently reported or summarized. We conducted a systematic review of the literature using Pubmed/Medline and EMBASE (1990-2020) for studies reporting estimates of out-of-pocket costs or qualitative estimates of financial burden on families during a neonatal intensive care unit stay or after discharge. 44 studies met inclusion criteria, with 25 studies providing cost estimates. Cost estimates primarily focused on direct non-medical out-of-pocket costs or loss of productivity, and there was a paucity of cost estimates for insurance cost-sharing. Available estimates suggest these costs are significant to families, cause significant stress, and may impact care received by patients. More high-quality studies estimating the entirety of out-of-pocket costs are needed, and particular attention should be paid to how these costs directly impact the care of our high-risk population.

Economic evaluations performed alongside randomized controlled trials benefit from the protections against bias inherent in randomization. In this systematic review, we assessed the frequency and quality of economic assessments alongside randomized controlled trials of interventions in neonates published between 1990 and 2016. Over that period, 58 economic assessments were published, corresponding to approximately 2% of RCTs. We noted significant methodological limitations of these studies, including limitation of included costs to the health sector or payer rather than broader categories such as family or community expenditures (81%), short time horizon for cost measurement (less than one year in 60%), lack of reporting of uncertainty (26%), and infrequent analysis of costs and effects in a single metric (combined in 45%). Strategies for improving the quality and frequency of economic evaluations in neonatology are discussed, including selection of appropriate trials, funding, and peer review.

Multiunit housing (MUH) residents are particularly susceptible to involuntary secondhand smoke (SHS) exposure in their home, which can enter their living units from nearby units and shared areas where smoking occurs. To date, no study has assessed non-cigarette tobacco use among MUH residents. This study assessed the prevalence and sociodemographic correlates of tobacco use (combustible, noncombustible, any tobacco use including electronic cigarettes), smoke-free home rules, and SHS incursions among U.S. MUH residents.Data came from the 2013-2014 National Adult Tobacco Survey, a telephone survey of U.S. adults aged ≥18 years. Analyses were conducted in 2015. Prevalence of current tobacco use and smoke-free home rules were assessed overall and by sociodemographics, stratified by housing type (single family versus MUH). Prevalence and adjusted odds of SHS incursions among MUH residents with smoke-free home rules were assessed.Tobacco use was higher among adults living in MUH (24.7%) than those in single-family housing (18.9%, p0.05). Smoke-free home rules were higher among adults living in single-family housing (86.7%) than those in MUH (80.9%, p0.05). Among MUH residents with smoke-free homes, 34.4% experienced SHS incursions. Adjusted odds of SHS incursions were greater among women, younger adults, non-Hispanic blacks, Hispanics, and those with lower income.One quarter of MUH residents use tobacco, and one third of MUH residents with smoke-free rules experience SHS incursions. Interventions are warranted to promote tobacco cessation and smoke-free building policies to protect all MUH residents, employees, and visitors from the dangers of tobacco use and SHS.

Curiosity is a potential risk factor for electronic cigarette (e-cigarette) use, which has increased considerably among US youth in recent years. We examined the relationship between curiosity about e-cigarettes and perceived harm, comparative addictiveness, and e-cigarette advertisement exposure. Data came from the 2014 National Youth Tobacco Survey, a nationally representative survey of U.S. middle and high school students. In 2014, 2.5% of middle school and 9.2% of high school students currently used cigarettes, while 3.9% of middle school and 13.4% of high school students reported current e-cigarette use. Among never e-cigarette users (n=17,286), descriptive statistics assessed curiosity about e-cigarettes by combustible tobacco use, sex, race/ethnicity, and school level. Associations between curiosity and perceived harm (absolute and comparative to cigarettes), comparative addictiveness, and e-cigarette advertising exposure were explored using multivariate models in 2015. Among youth who never used e-cigarettes, 25.8% reported curiosity about e-cigarettes. Higher levels of perceived absolute harm and comparative harm were associated with lower levels of curiosity, while no association was observed between comparative addictiveness and curiosity. Among never combustible tobacco users, the odds of high curiosity were greater among non-Hispanic blacks (odds ratio (OR): 1.39; 95% confidence interval (CI):1.02-1.88), Hispanics (OR=1.79; 95% CI:1.48-2.16), and non-Hispanic 'Other' (OR=1.47; 95% CI:1.15-1.89) race/ethnicities than non-Hispanic whites. One-quarter of middle and high school students who have never used e-cigarettes are curious about the products, with greater curiosity among those with lower perceptions of harm from these products. These findings may help inform future strategies aimed at reducing curiosity about e-cigarettes among youth.

The following study describes a technique to improve maritime search area prediction by using consensus forecasting to quantify areas of higher probability within a model defined search area. The study included forecasting search areas for 45 five-day drifter tracks, each simulated independently using different ocean models (BLUElink, FOAM, HYCOM and NCOM) throughout 2012 in the eastern Indian Ocean, off the coast of Western Australia. It was found that zones where all four model search areas overlapped (defined here as a consensus search area) were significantly smaller than those areas generated by any single model forecast. The average consensus search area was quantified to be up to 56.9% smaller at 24 h and 72.5% smaller at 120 h than the average single model search areas at corresponding times. However the average hit rate (the frequency that the drifter was contained within the forecast search area) for the consensus search area was reduced by up to 26.2% at 24 h and 52.8% at 120 h, when compared to average hit rates from single model search areas. This indicated that the four model consensus search area had a higher hit rate per unit of search area than any individual model search area. Hence if search resources were a limiting factor for a particular search effort, then search resources may be most effectively deployed by prioritising the effort initially to the smaller, four model consensus search area.

Introduction Policies legalizing marijuana for medical and recreational use have been increasing in the U.S. Considering the potential impact of these policies, important knowledge gaps exist, including information about the prevalence of various modes of marijuana use (e.g., smoked in joints, bowls, bongs; consumed in edibles or drinks) and about medical versus recreational use. Accordingly, this study assessed (1) prevalence and correlates of modes of current and ever marijuana use and (2) prevalence of medicinal and recreational marijuana use in U.S. adults. Methods Data came from Summer Styles ( n =4,269), a nationally representative consumer panel survey of adults aged ≥18 years, collected in 2014. The survey asked about past 30–day (current) and ever mode of marijuana use and current reason for use (medicinal, recreational, both). Weighted prevalence estimates were computed and correlates were assessed in 2014 using logistic regression. Results Overall, 7.2% of respondents reported current marijuana use; 34.5% reported ever use. Among current users, 10.5% reported medicinal-only use, 53.4% reported recreational-only use, and 36.1% reported both. Use of bowl or pipe (49.5%) and joint (49.2%) predominated among current marijuana users, with lesser use of bong, water pipe, or hookah (21.7%); blunts (20.3%); edibles/drinks (16.1%); and vaporizers (7.6%); 92.1% of the sample reported combusted-only marijuana use. Conclusion Combusted modes of marijuana use are most prevalent among U.S. adults, with a majority using marijuana for recreation. In light of changing policies and patterns of use, improved marijuana surveillance is critical for public health planning.

To assess the prevalence and characteristics of smoke-free home and vehicle rules by tobacco use.Data came from the 2012-2013 National Adult Tobacco Survey, a telephone survey of adults aged ≥18. Respondents who reported smoking is 'never allowed' inside their home or any family vehicle were considered to have smoke-free home and vehicle rules, respectively. Prevalence and characteristics of smoke-free rules were assessed overall and by current tobacco use (combustible only, noncombustible only, combustible and noncombustible, no current tobacco use). Assessed characteristics included: sex, age, race/ethnicity, education, marital status, income, region, and sexual orientation.Nationally, 83.7% of adults (n=48,871) had smoke-free home rules and 78.1% (n=46,183) had smoke-free vehicle rules. By tobacco use, prevalence was highest among nonusers of tobacco (homes: 90.8%; vehicles: 88.9%) and lowest among combustible-only users (homes: 53.7%; vehicles: 34.2%). Prevalence of smoke-free home and vehicle rules was higher among males, adults with a graduate degree, and adults living in the West.Most adults have smoke-free home and vehicle rules, but differences exist by tobacco use. Opportunities exist to educate adults about the dangers of secondhand smoke and the benefits of smoke-free environments, particularly among combustible tobacco users.

Purinergic Signalling in the Enteric Nervous System involves the regulated release of ATP (or a structurally-related nucleotide) which activates an extensive suite of membrane-inserted receptors (P2X and P2Y subtypes) on a variety of cell types in the gastrointestinal tract. P2X receptors are gated ion-channels permeable to sodium, potassium and calcium. They depolarise cells, act as a pathway for calcium influx to activate calcium-dependent processes and initiate gene transcription, interact at a molecular level as a form of self-regulation with lipids within the cell wall (e.g. PIP2) and cross-react with other membrane-inserted receptors to regulate their activity (e.g. nAChRs). P2Y receptors are metabotropic receptors that couple to G-proteins. They may release calcium ions from intracellular stores to activate calcium-dependent processes, but also may activate calcium-independent signalling pathways and influence gene transcription. Originally ATP was a candidate only for NANC neurotransmission, for inhibitory motoneurons supplying the muscularis externa of the gastrointestinal tract and bringing about the fast IJP. Purinergic signalling later included neuron-neuron signalling in the ENS, via the production of either fast or slow EPSPs. Later still, purinergic signalling included the neuro-epithelial synapse-for efferent signalling to epithelia cells participating in secretion and absorption, and afferent signalling for chemoreception and mechanoreception at the surface of the mucosa. Many aspects of purinergic signalling have since been addressed in a series of highly-focussed and authoritative reviews. In this overview however, the current focus is on key aspects of purinergic signalling where there remains uncertainty and ambiguity, with the view to stimulating further research in these areas.

Heterologous expression of many proteins in bacteria, yeasts, and plants is often limited by low titers of functional protein. To address this problem, we have created a two-tiered directed evolution strategy in Escherichia coli that enables optimization of protein production while maintaining high biological activity. The first tier involves a genetic selection for intracellular protein stability that is based on the folding quality control mechanism inherent to the twin-arginine translocation pathway, while the second is a semi-high-throughput screen for protein function. To demonstrate the utility of this strategy, we isolated variants of the endoglucanase Cel5A, from the plant-pathogenic fungus Fusarium graminearum, whose production was increased by as much as 30-fold over the parental enzyme. This gain in production was attributed to just two amino acid substitutions, and it was isolated after two iterations through the two-tiered approach. There was no significant tradeoff in activity on soluble or insoluble cellulose substrates. Importantly, by combining the folding filter afforded by the twin-arginine translocation quality control mechanism with a function-based screen, we show enrichment for variants with increased protein abundance in a manner that does not compromise catalytic activity, providing a highly soluble parent for engineering of improved or new function.

Menthol can mask the harshness and taste of tobacco, making menthol cigarettes easier to use and increasing their appeal among vulnerable populations. The tobacco industry has targeted youth, women, and racial minorities with menthol cigarettes, and these groups smoke menthol cigarettes at higher rates. The tobacco industry has also targeted the lesbian, gay, bisexual, and transgender (LGBT) communities with tobacco product marketing.To assess current menthol cigarette smoking by sexual orientation among a nationally representative sample of U.S. adults.Data were obtained from the 2009-2010 National Adult Tobacco Survey, a national landline and cellular telephone survey of non-institutionalized U.S. adults aged ≥18 years, to compare current menthol cigarette smoking between LGBT (n=2,431) and heterosexual/straight (n=110,841) adults. Data were analyzed during January-April 2014 using descriptive statistics and logistic regression adjusted for sex, age, race, and educational attainment.Among all current cigarette smokers, 29.6% reported usually smoking menthol cigarettes in the past 30 days. Menthol use was significantly higher among LGBT smokers, with 36.3% reporting that the cigarettes they usually smoked were menthol compared to 29.3% of heterosexual/straight smokers (p0.05); this difference was particularly prominent among LGBT females (42.9%) compared to heterosexual/straight women (32.4%) (p0.05). Following adjustment, LGBT smokers had greater odds of usually smoking menthol cigarettes than heterosexual/straight smokers (OR=1.31, 95% CI=1.09, 1.57).These findings suggest that efforts to reduce menthol cigarette use may have the potential to reduce tobacco use and tobacco-related disease and death among LGBT adults.

Background Increasing diversity of the tobacco product landscape, including electronic cigarettes (e-cigarettes), hookah, snus, and dissolvable tobacco products (dissolvables), raises concerns about the public health impact of these non-conventional tobacco products among youth. Purpose This study assessed awareness, ever use, and current use of non-conventional tobacco products among U.S. students in 2012, overall and by demographic and tobacco use characteristics. Methods Data from the 2012 National Youth Tobacco Survey, a nationally representative survey of U.S. middle and high school students, were analyzed in 2013. Prevalence of awareness, ever use, and current use of e-cigarettes, hookah, snus, and dissolvables were calculated overall and by sex, school level, race/ethnicity, and conventional tobacco product use, including cigarettes, cigars, or smokeless tobacco (chewing tobacco, snuff, or dip). Results Overall, 50.3% of students were aware of e-cigarettes; prevalence of ever and current use of e-cigarettes was 6.8% and 2.1%, respectively. Awareness of hookah was 41.2% among all students, and that of ever and current use were 8.9% and 3.6%, respectively. Overall awareness; ever; and current use of snus (32%, 5.3%, 1.7%, respectively) and dissolvables (19.3%, 2.0%, 0.7%, respectively) were generally lower than those of e-cigarettes or hookah. Conventional tobacco product users were more likely to be aware of and to use non-conventional tobacco products. Conclusions Many U.S. students are aware of and use non-conventional tobacco products. Evidence-based interventions should be implemented to prevent and reduce all tobacco use among youth.

Background Among U.S. youth overall, cigars are the most commonly used tobacco product after cigarettes. However, youth who identify their products by brand names, not general terms like "cigar," may underreport use. Purpose To examine changes in reported cigar (cigar, cigarillo, or little cigar) smoking among students following inclusion of cigar brand examples on the National Youth Tobacco Survey (NYTS). Methods Data from the 2011 and 2012 NYTS and National Survey on Drug Use and Health (NSDUH) were analyzed in 2013 to estimate ever and current cigar smoking, overall and by race/ethnicity. The 2012 NYTS included cigar brand examples (Black and Mild, Swisher Sweets, Dutch Masters, White Owl, Phillies Blunt) in the survey instructions and ever use question, but the 2011 NYTS and 2011 and 2012 NSDUH did not. Results NYTS ever cigar smoking was higher in 2012 (27.8%) than 2011 (19.5%) among black students overall. Current cigar smoking was 60%–70% higher among black females and students aged ≥17 years, in 2012 than 2011. For black females, current cigar smoking (11.5%) was two times greater than that of white females (4.3%) in 2012, whereas the prevalence among these subgroups was comparable in 2011. Similar changes were not observed among these subgroups in the 2011–2012 NSDUH. Conclusions This study highlights the high burden of cigar use among U.S. youth and suggests that NYTS ascertainment of cigar smoking may have improved by including brands. Disparities in cigar smoking need to be addressed to prevent and reduce all youth tobacco use.

Purpose: Flavors can mask the harshness and taste of tobacco, making flavored tobacco products appealing to youth. We assessed the prevalence and correlates of flavored-little-cigar and flavoredcigarette use among U.S. middle and high school students in 2011. Methods: Data were obtained from the 2011 National Youth Tobacco Survey, a nationally representative school-based survey of U.S. students in grades 6e12. National estimates of current flavored-little-cigar use, flavored-cigarette use, and combined use of either product were calculated overall and among current smokers by respondent characteristics, including sex, race/ ethnicity, school level, and grade. Additionally, intention to quit tobacco and smoking frequency were assessed by flavored product use. Results: The overall prevalence of current use was 4.2% for flavored cigarettes, 3.3% for flavored little cigars, and 6.3% for either product. Among current cigar smokers, 35.9% reported using flavored little cigars, and among current cigarette smokers, 35.4% reported using flavored cigarettes. Among current cigar or cigarette smokers, 42.4% reported using flavored little cigars or flavored cigarettes. Flavored product use among current smokers was higher among non-Hispanic whites than among blacks and Hispanics, higher among high school students than middle school students, and increased with grade. Among cigar smokers, prevalence of no intention to quit tobacco was higher among flavored-little-cigar users (59.7%) than nonusers (49.3%). Conclusions: More than two fifths of U.S. middle and high school smokers report using flavored little cigars or flavored cigarettes, and disparities in the use of these products exist across subpopulations. Efforts are needed to reduce flavored tobacco product use among youth.

article i nfo Background. Most tobacco use begins during youth. Thus, this study assessed the prevalence, trends, and correlates of pro-tobacco advertising among United States students in grades 6-12 during 2000-2012. Methods. Data from the 2000-2012 National Youth Tobacco Survey were analyzed to assess self-reported exposure to pro-tobacco advertisements through three media: over the Internet, in newspapers/magazines, and at retail stores. Trends during 2000-2012 were assessed in a binary logistic regression model (P b 0.05). Results. Among all middle and high school students, the overall prevalence of exposure to Internet pro- tobacco advertisements increased from 22.3% to 43.0% during 2000-2012 (P b 0.001 for linear trend). During the same period, declines were observed in the overall prevalence of exposure to pro-tobacco advertisements in newspapers/magazines (65.0% to 36.9%) and at retail stores (87.8% to 76.2%) (P b 0.001 for all linear trends). Conclusion. Exposure to pro-tobacco advertisements over the Internet increased significantly during 2000-2012 among United States middle and high school students, while a decline in exposure to advertisements in newspapers or magazines, and at retail stores occurred during the sameperiod. However, over two-thirds of stu- dents still reported retail store exposure to pro-tobacco advertisements in 2012. Enhanced and sustained efforts would be beneficial to reduce even more exposure to all forms of pro-tobacco advertisements among youths.

An accurate understanding of the leeway drift characteristics of drifting objects is required to effectively forecast the drift of persons, vessels or objects lost at sea, and to generate efficient search areas to maximise the probability of successfully locating those missing. Presently, the most effective method for calculating the leeway drift characteristics of an object or vessel is to empirically derive the leeway coefficients of that object through field studies. The main goal of the studies is to measure how the object drifts in relation to the surface currents, due to the wind and wave action upon it. This paper outlines the determination of downwind and crosswind leeway coefficients for three small craft common to Pacific island communities for which no accurate leeway coefficients exist. These craft were: a 19 foot (5.8 m) fibreglass skiff (known locally as pangas, fibres, or banana boats); a 20 foot (5.97 m) fibreglass outrigger canoe; and a 2-person sit down personal water craft (PWC). Due to the vast distances between pacific islands and the remoteness of these locations it can be several days until a search can be mounted to rescue those lost at sea, hence it is paramount that an accurate description of the drift of these tropical pacific craft is available for use in search and rescue (SAR) drift models, to define appropriate search areas. This study successfully derived the leeway coefficients required for each of these three craft. The leeway speed of the outrigger canoe and PWC, both with one person on board (POB) equivalent loading, were calculated to be 2.40% and 4.24% of the wind speed respectively. The leeway speed of the skiff was found to range between 7.71% and 4.40% of the wind speed for equivalent loading between 1 POB and 13 POB. The results of these field tests have subsequently been implemented into search and rescue models by several SAR organisations worldwide. These results show that the findings herein have the potential to both increase the likelihood of finding persons adrift at sea alive, as well as reducing search costs through more effective drift prediction and efficient search area formulation.

Using inverse methods a circulation for a new section along 32°S in the Indian Ocean is derived with a maximum in the overturning stream function (or deep overturning) of 10.3 Sv at 3310 m. Shipboard and Lowered Acoustic Doppler Current Profiler (ADCP) data are used to inform the choice of reference level velocity for the initial geostrophic field. Our preferred solution includes a silicate constraint (−312 ± 380 kmol s−1) consistent with an Indonesian throughflow of 12 Sv. The overturning changes from 12.3 Sv at 3270 m when the silicate constraint is omitted to 10.3 Sv when it is included. The deep overturning varies by only ±0.7 Sv as the silicate constraint varies from +68 to −692 kmol s−1, and by ±0.3 Sv as the net flux across the section, driven by the Indonesian throughflow, varies from −7 to −17 Sv with an appropriately scaled silicate flux constraint. Thus, the overturning is insensitive to the size of the Indonesian throughflow and silicate constraint within their apriori uncertainties. We find that the use of the ADCP data adds significant detail to the horizontal circulation. These resolved circulations include the Agulhas Undercurrent, deep cyclonic gyres and deep fronts, features evidenced by long term integrators of the flow such as current meter and float measurements as well as water properties.

Venture capitalists are often lauded, as well as sought after, for their expertise as strategists. How they influence the direction of the firms they invest in is well understood, but how they develop strategy for their own firms has received limited attention in the literature. This study adopts a strategy as practice perspective and examines decision making processes at leading venture capital firms in Boston and Silicon Valley. Three main ideas are advanced. First, that venture capitalists are ‘bifurcated strategists’, using planning for their portfolio companies, while using emergent strategies on their own behalf. Second, that some leading firms use deliberately emergent strategies, a finding that is consistent with other empirical studies of strategizing in turbulent environments. Finally, a dynamic model is proposed showing how these strategies are put into practice.

P2X receptors are cation-selective, ligand-gated ion channels activated by synaptically released, extracellular adenosine 5'-triphosphate (ATP). ATP-gated currents are inhibited by ethanol when tested in dorsal root ganglion and CA1 neurons. Recently, we reported differences in sensitivity to ethanol inhibition between homomeric P2X(2) and P2X(4) receptors expressed in Xenopus oocytes, which suggested that subunit composition of native P2X receptors determines their ethanol sensitivity. The present study extended the investigation to P2X(3) receptors. The effects of ethanol and zinc ions (Zn(2+)) were tested on homomeric P2X(3) and P2X(4) receptors expressed in Xenopus oocytes using two-electrode voltage clamp. Ethanol potentiated ATP-gated P2X(3) receptor currents in a concentration dependent manner. In contrast, ethanol inhibited P2X(4) receptor function. Ethanol did not directly alter receptor function, nor did it alter the Hill coefficient or maximal ATP response (E(max)) in either P2X(3) or P2X(4) receptors. Ethanol increased the maximal response to Zn(2+) ATP-gated currents in P2X3 receptors which suggests that ethanol and Zn(2+) act on different sites. The differences in ethanol response of P2X(3) and P2X(4) receptors set the stage for future investigations that will use chimeric P2X receptors or other molecular manipulations of P2X structure to investigate the molecular sites and mechanisms of action of ethanol.

A method to model the influence of a hydraulic structure connecting two water bodies is presented. This method was incorporated into an existing two-dimensional (depth-averaged) hydrodynamic model. Specifically, the flow in and out of a cell (used to represent the hydraulic structure) is calculated using a broad crested weir formula and is determined from the time-varying head difference between the two systems. An example application of the method is also presented. In this example the hydraulic structure cell was used to model the flow through an automated bi-directional hydraulic structure connecting an estuary to an artificial lake system. The gates of this hydraulic structure are programmed to open four times each day (once during each semi-diurnal tidal phase) and remain open for a period of 2 hours, allowing alternative and partial exchange between the two water bodies. Hence, the model setup involved the specification of the opening and closing times of the gates and the calibration of the discharge coefficient. Tests indicated that these were the most sensitive parameters which ensured the correct volume of water exchange between the two systems. Finally, the model-predicted results were compared with available surface elevation observations at two sites within the lake. The comparison showed a good agreement (RMS error

The cloning of a human G-protein-coupled receptor (GPCR) that specifically responds to UDP-glucose and related sugar-nucleotides has been reported recently. This receptor has important structural similarities to known members of the P2Y receptor family but also shows a distinctly different pharmacological response profile. Here, the IUPHAR Subcommittee for P2Y receptor nomenclature and classification review the current knowledge of this receptor and present their reasons for including this receptor in the P2Y receptor family as the P2Y(14) receptor.

The beginning of the last decade heralded three important and sequential developments in our understanding of cell-to-cell signalling by extracellular ATP via its cell surface receptors, the P2 purinoceptors. One major development in ATP signalling culminated in a timely review in 1991, when it was established in the clearest of terms that ATP receptors exploited discrete signal transduction pathways (Dubyak, G.R., 1991. Signal transduction by P2-purinergic receptors for extracellular ATP. Am. J. Respir. Cell. Mol. Biol. 4, 295–300; and later in Dubyak, G.R., El-Moatassim, C., 1993. Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am. J. Physiol. 265, C577–C606). Henceforth, it was universally acknowledged that some P2 purinoceptors interacted with heterotrimeric G-proteins to activate intracellular signalling cascades (metabotropic ATP receptors), whereas others contained intrinsic ion-channels (ionotropic ATP receptors). A second key development can be traced to 1992, from the discovery that ATP receptors were involved in excitatory neurotransmission in the CNS and PNS (Edwards, F.A., Gibb, A.J., Colquhoun, D., 1992. ATP receptor-mediated synaptic currents in the central nervous system. Nature 359, 144–147; Evans, R.J., Derkach, V., Surprenant, A., 1992. ATP mediates fast synaptic transmission in mammalian neurons. Nature 357, 503–505; Silinsky, E.M., Gerzanich, V., Vanner, S.M., 1992. ATP mediates excitatory synaptic transmission in mammalian neurones. Br. J. Pharmacol., 106, 762–763). Thereafter, it was accepted that ATP could play a neurotransmitter and/or modulatory role throughout the entire nervous system. The third key development stemmed from the isolation of a cDNA, from chick brain, encoding a metabotropic ATP receptor (Webb, T.E., Simon, J., Krishek, B.J., Bateson, A.N., Smart, T.G., King, B.F., Burnstock, G., Barnard, E.A., 1993. Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett. 324, 219–225). The cloning of a membrane protein serving as an ATP receptor ignited a widespread international interest in purinergic signalling. Investigators at University College London (UCL) — colleagues and associates of Geoffrey Burnstock — were at the forefront of this rapid phase of discovery. In this review, we highlight the UCL experience when the fields of molecular biology, physiology and cell biology converged to help advance our understanding of ATP as an extracellular signalling molecule.

A method of recording four quadrature-reference-wave-holograms by CCD and reconstructing the object wave front by numerical calculation is presented in this paper. The terms of direct transmitting, auto-correlation and conjugate wave in the four reconstructing waves are cancelled out and only the original object wave is left after overlapping. Reconstructed images are obtained by calculating through Fresnel–Kirchhoff integral on computers. The influences of the noise of CCD and the phase-shifting error of phase-shift elements to the quality of the reconstructed images are analyzed. Experimental results show that pure original object wave or the conjugate object wave can be reconstructed in in-line holograms using the method in this paper.

We have cloned and functionally characterised the mouse orthologue of the P2X4 receptor, mP2X4, and a splice variant of this receptor, mP2X4a. mP2X4 is 388 amino acids in length and shares 94% and 87% identity with the rat and human P2X4 receptors, respectively, while mP2X4a is 361 amino acids in length and lacks a 27-amino acid region in the extracellular domain corresponding to exon 6 of the known P2X receptor gene structures. When expressed in Xenopus laevis oocytes, mP2X4 produces a rapid inward current in response to ATP with an EC50 of 1.68+/-0.2 microM, consistent with the affinity of the rat and human P2X4 receptors for ATP. This agonist response is potentiated by the P2X receptor antagonists suramin, Reactive blue 2 and, over a limited concentration range, by PPADS. Although mP2X4a forms a poorly functional homomeric receptor, it appears able to interact with the full-length mP2X4 subunit to result in a functional channel with a reduced affinity for ATP. These results suggest a possible role for splice variants of P2X receptors in the formation of functional heteromeric ion channels.

Hydrographic data from the World Ocean Circulation Experiment (WOCE) and South Atlantic Ventilation Experiment (SAVE) in the region of transition between the Scotia Sea and the Argentine Basin are examined to determine the composition of the deep water from the Southern Ocean that enters the Atlantic, and to describe the pathways of its constituents. The deep current that flows westward against the Falkland Escarpment is formed of several superposed velocity cores that convey waters of different origins: Lower Circumpolar Deep Water (LCDW), Southeast Pacific Deep Water (SPDW), and Weddell Sea Deep Water (WSDW). Different routes followed by the WSDW upstream of, and through, the Georgia Basin, lead to distinctions between the Lower-WSDW (σ4>46.09) and the Upper-WSDW (46.04

Background: The 5-HT 3 receptor is a serotonin receptor believed to reside on enteric neurons. However, several studies belie an exclusive neural localization. Our hypothesis is that the 5-HT 3 receptor agonist, 2-methyl-5-HT (2Me5HT), induces chloride secretion despite neural blockade, which can be blocked by a 5-HT 3 receptor antagonist. Methods: Rat distal colon was stripped of its muscularis, mounted as mucosal sheets in Ussing chambers, and short-circuited. Adjacent sheets were pretreated with 1 μmol/L of the neurotoxin, tetrodotoxin, and incubated with 2Me5HT (50 μmol/L) alone or with a 5-HT 3 (0.3 μmol/L ondansetron or 0.3 μmol/L tropisetron) or a 5-HT 4 (0.3 μmol/L GR11808) receptor antagonist. Short-circuit current (I sc ) was measured continuously. Results: 2Me5HT caused an increase in I sc , which was significantly (P

The aim of the present study was to examine the effects of a number of P2-purinoceptor antagonists on degradation of adenine nucleotides by Xenopus laevis oocyte ecto-nucleotidase. Folliculated oocytes readily metabolize all three naturally-occurring nucleotides, the order of preferential substrates being ATPADPAMP. The degradation of ATP and ADP was decreased significantly in the presence of several P2X- and P2Y-purinoceptor antagonists, including suramin, PPADS, Cibacron blue, Coomassie Brilliant blue, Evans blue, Trypan blue, Congo red, and PIT (each compound was used at 100 microM). All these compounds inhibited the degradation of ATP by up to 60%, whereas the hydrolysis of ADP was inhibited by Congo red and PIT by 75-80%. In addition, DIDS (100 microM) and TNP-ATP (100 microM) selectively inhibited the breakdown of ATP, and sodium azide (10 mM) selectively inhibited the breakdown of ADP. The enzymatic breakdown of either ATP or ADP was unaffected by 8-pSPT (100 microM), an antagonist of P1-purinoceptors, or by oxidized ATP (100 microM), an antagonist of P2Z-purinoceptors. The degradation of AMP was prevented completely by PIT (100 microM) and ingibited significantly by Congo red (100 microM). In conclusion, the present study shows that most of currently available antagonists of P2-purinoceptors inhibit the enzymatic breakdown of extracellular ATP and ADP. The inhibitory effect on ecto-nucleotidase activity should be taken into account when these antagonists are used in pharmacological experiments.

The role of prejunctional purinoceptors (P 1 -subtype) in the control of ATP-release from inhibitory motoneurons was investigated electrophysiologically, by studying fast purinergic inhibitory junction potentials (IJPs) in guinea-pig ileal circular muscle. Pressure ejections of adenosine and ATP (but not of α, β-methylene ATP) onto circular muscle depressed the amplitude of fast IJPs, indicating the presence of prejunctional P 1 -purinoceptors. An adenosine (A 1/2 )-receptor antagonist, theophylline (10 −8 –10 −4 M), increased the amplitude of fast IJPs in a dose-related manner (EC 50 − 17.5 μM), suggesting the existence of a basal ‘adenosine tone’ that regulated ATP-release from ileal motoneurons. However, three methylxanthine derivatives, caffeine (10 −8 –10 −4 M), 3-isobutyl-1-methylxanthine (IBMX; 10 −8 –10 −4 M) and the potent A 1 -receptor antagonist 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (DPCPX; 10 −8 –10 −4 M), failed to potentiate fast IJPs and placed in doubt the existence of this inhibitory adenosine tone. Caffeine and IBMX, but not DCPCX, hyperpolarised ileal circular muscle in a dose-related manner and reduced IJP-amplitude; DPCPX did not alter the amplitude of IJPs. The non-specific inhibitor of phosphodiesterases, Ro-20-1724 (5 × 10 −7 –5 × 10 −5 M ), increased the amplitude of fast. IJPs, mimicking the actions of theophylline. To this extent, facilitation of inhibitory transmission appeared to involve phosphodiesterase inhibition and modification of intra-axonal cAMP levels and phosphorylation of intra-axonal protein kinases. The phenomenon of IJP rundown, presumed to be a manifestation of prejunctional autoinhibition, was studied using theophylline and DPCPX as A 1 -receptor antagonists. Theophylline enhanced the extent of IJP rundown, while the more potent A 1 -antagonist DPCPX was inactive, suggesting that IJP-rundown did not involve P 1 /A 1 -receptors. It was concluded that P 1 -purinoceptors do not play a significant role in the regulation of evoked ATP-release, at least at low stimulus rates of less than 2 Hz, although P 1 purinoceptors were present on motoneurons. Instead, there appears to be another mechanism, regulated by intra-axonal phosphodiesterases and involving cAMP, that controls ATP-release from ileal motoneurons.

Considered are sets of the first category whose images under similarities are of the first category. It has been established that if A is a dense set of the first category then every set similar to A is of the first category. Established here is that the homeomorphic images of such sets are of the first category. Also considered are their ordered unions, their dense subsets, and noted is the difference between these kinds of sets and the notion of a set always of the first category. Lastly consideration is given towards sets always classified as nowhere dense.