A close-pair binary in a distant triple supermassive black hole system.

Galaxies are believed to evolve through merging, which should lead to some hosting multiple supermassive black holes. There are four known triple black hole systems, with the closest black hole pair being 2.4 kiloparsecs apart (the third component in this system is at 3 kiloparsecs), which is far from the gravitational sphere of influence (about 100 parsecs for a black hole with mass one billion times that of the Sun). Previous searches for compact black hole systems concluded that they were rare, with the tightest binary system having a separation of 7 parsecs (ref. 10). Here we report observations of a triple black hole system at redshift z = 0.39, with the closest pair separated by about 140 parsecs and significantly more distant from Earth than any other known binary of comparable orbital separation. The effect of the tight pair is to introduce a rotationally symmetric helical modulation on the structure of the large-scale radio jets, which provides a useful way to search for other tight pairs without needing extremely high resolution observations. As we found this tight pair after searching only six galaxies, we conclude that tight pairs are more common than hitherto believed, which is an important observational constraint for low-frequency gravitational wave experiments.

Electronic cigarette use in young people in Great Britain 2013-2014.

OBJECTIVES: The recent growth in the market for electronic cigarettes (e-cigarettes) has led to concerns over their use by young people. It is therefore important to examine trends in the perception and use of e-cigarettes and conventional cigarettes in this group. STUDY DESIGN: Two-wave cross-sectional survey design. METHODS: Young people aged 11-18 in Great Britain were surveyed online by YouGov in 2013 and 2014. Use of e-cigarettes, together with perceived health harms and intention to use were assessed and compared in relation to cigarette smoking history, age and gender. RESULTS: Ever-use of e-cigarettes increased significantly from 4.6% (95% CI 3.8-5.7) in 2013 to 8.2% (95% CI 7.0-9.6) in 2014. Monthly or more use of e-cigarettes increased from 0.9% (95% CI 0.5-1.5) to 1.7 (1.2-2.4), but remained rare in never-smokers at under 0.2%. The proportion of young people who perceived e-cigarettes to be less harmful to users than cigarettes fell from 73.4% (95% CI 71.0-75.8) to 66.9% (95% CI 64.5-69.2), while the proportion who considered e-cigarettes to cause similar levels of harm increased from 11.8% (95% CI 10.0-13.5) to 18.2% (95% CI 16.3-20.1). Of the 8.2% of e-cigarette ever-users in 2014, 69.8% (95% CI 62.2%-77.3%) had smoked a cigarette prior to using an e-cigarette, while 8.2% (95% CI 4.1%-12.2%) first smoked a cigarette after e-cigarette use. CONCLUSIONS: A growing proportion of young people in Great Britain believe e-cigarettes are as harmful as smoking tobacco. Use of e-cigarettes by young people is increasing, but is largely confined to those who smoke.

Smoke-free homes in England: prevalence, trends and validation by cotinine in children.

OBJECTIVE: To examine the prevalence of smoke-free homes in England between 1996 and 2007 and their impact on children's exposure to second-hand smoke via a series of annual cross-sectional surveys: the Health Survey for England. These comprised nationally representative samples of non-smoking children aged 4-15 (n = 13 365) and their parents interviewed in the home. Main outcome measures were cotinine measured in saliva, smoke-free homes defined by "no" response to "Does anyone smoke inside this house/flat on most days?", self-reported smoking status of parents and self-reported and cotinine validated smoking status in children. RESULTS: The proportion of homes where one parent was a smoker that were smoke free increased from 21% in 1996 to 37% in 2007, and where both parents were smokers from 6% to 21%. The overwhelming majority of homes with non-smoking parents were smoke free (95% in 1996; 99% in 2007). For children with non-smoking parents and living in a smoke-free home the geometric mean cotinine across all years was 0.22 ng/ml. For children with one smoking parent geometric mean cotinine levels were 0.37 ng/ml when the home was smoke free and 1.67 ng/ml when there was smoking in the home; and for those with two smoking parents, 0.71 ng/ml and 2.46 ng/ml. There were strong trends across years for declines in cotinine concentrations in children in smoke-free homes for the children of smokers and non-smokers. CONCLUSIONS: There has been a marked secular trend towards smoke-free homes, even when parents themselves are smokers. Living in a smoke-free home offers children a considerable, but not complete, degree of protection against exposure to parental smoking.

Vulnerability to smoking after trying a single cigarette can lie dormant for three years or more.

OBJECTIVE: To examine the development of smoking behaviour among adolescents who, at age 11, had tried cigarettes just once. DESIGN: A five-year prospective study. SETTING: 36 schools in South London, England. SUBJECTS: A socioeconomically and ethnically diverse sample of students completed questionnaires annually from age 11-16. A total of 5863 students took part, with an annual response rate ranging from 74-85%. 2041 (35%) provided smoking status data every year. MAIN OUTCOME MEASURES: Current smoking (smoking sometimes or more often) for the first time. Cotinine assays provided biochemical verification of smoking status. RESULTS: Students who at age 11 reported having tried smoking cigarettes just once (n = 260), but were not smoking at the time, were more likely to take-up smoking at a later age than those that had not tried smoking (n = 1719), even after a gap of up to three years of not smoking. The odds of starting to smoke at age 14 were 2.1 times greater (95% confidence interval 1.2 to 3.5) in the age 11 "one time triers" than the "non-triers", even once sex, ethnicity, deprivation, parental smoking and conduct disorder were adjusted for. CONCLUSIONS: This is the first clear demonstration of a "sleeper effect" or period of dormant vulnerability. Our findings have implications for understanding the development of cigarette use and for policies to reduce smoking in young people. Preventing children from trying even one cigarette may be important, and the design of interventions should recognise adolescents who have smoked just once, several years previously, as potentially vulnerable to later smoking uptake.

Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey.

BACKGROUND: The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers' nicotine intakes and exposure to cigarette toxins has been called into question. However, most studies of the relationship between nicotine yield and nicotine intake have been on relatively small and unrepresentative samples and have included few smokers of "ultra-low" brands (i.e., those yielding around 1 mg of tar and 0.1 mg of nicotine). METHODS: We examined the relationship between salivary cotinine (a major metabolite of nicotine) concentrations and nicotine yields of machine-smoked cigarettes in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. We used standard linear regression techniques to examine associations and two-sided tests of statistical significance. RESULTS: Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. On average, cotinine levels were slightly lower in smokers of lower nicotine-yielding brands, but these smokers differed in terms of sex, socioeconomic profile, and cigarette consumption. After we controlled for potential confounders, nicotine yield from the brand smoked accounted for only 0.79% of the variation in saliva cotinine concentrations. Nicotine intake per cigarette smoked, as estimated from salivary cotinine level, did not correspond with machine-smoked yields at any level of nicotine yield. Nicotine intake per cigarette was about eight times greater than machine-smoked yields at the lowest deliveries (1.17 mg estimated nicotine intake per cigarette from brands averaging 0.14-mg delivery from machine smoking) and 1.4 times greater for the highest yield cigarettes (1.31-mg estimated nicotine intake per cigarette from brands averaging 0.91 mg from machine smoking). CONCLUSIONS: Smokers' tendency to regulate nicotine intake vitiates potential health gains from lower tar and nicotine cigarettes. Current approaches to characterizing tar and nicotine yields of cigarettes provide a simplistic guide to smokers' exposure that is misleading to consumers and regulators alike and should be abandoned.

Toward a comprehensive long term nicotine policy.

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Factors determining exposure to passive smoking in young adults living at home: quantitative analysis using saliva cotinine concentrations.

Saliva cotinine concentrations were used to examine determinants of exposure to environmental tobacco smoke in 393 non-smoking students (age range 16-19 years) attending a sixth form college and living at home. Average concentrations were low (median 0.60 ng/ml), reflecting partly the warm weather at the time of the survey and partly the predominantly middle class sample. Despite this, cotinine levels were strongly related to the extent of self-reported passive smoking in the past three days (medians 0.30, 0.60, 0.90 and 1.35 ng/ml in those reporting 'None at all', 'A little', 'Some' and 'A lot' respectively, p less than 0.0001). Individual sources of environmental tobacco smoke identified were smoking by mothers (p less than 0.0001), by fathers (p less than 0.01), and exposure at college (p less than 0.001) and when out in the evenings (p less than 0.001). The results indicate that exposure outside the home may become of equal or greater importance than family smoking in determining the overall passive smoking dose received by this age group.

Maternal cotinine level during pregnancy and birthweight for gestational age.

BACKGROUND: Recent studies have found that cotinine is a better predictor of birthweight than the number of cigarettes smoked in pregnancy. In this paper we test this hypothesis and use cotinine to explore the effect of environmental tobacco smoke (ETS) on birthweight. METHODS: In all, 1254 white women were interviewed at booking, 28 and 36 weeks about the number and brand of cigarette smoked. Cotinine was assayed from blood samples taken on the day of interview. The outcome was birthweight for gestational age. RESULTS: There was good agreement between self-reported smoker/non-smoker status and maternal cotinine with 1.3% women mis-reported as non-smokers at booking, 0.6% and 1.8% mis-reported at 28 and 36 weeks respectively. Among smokers, cotinine was more closely related to birthweight than the number of cigarettes smoked at all three time points (r = -0.25 versus r = -0.16 at booking). A reduction in cotinine between booking and 28 weeks was associated with increased birthweight but the effect was not statistically significant. Among non-smokers the association between birthweight and cotinine was not statistically significant after adjusting for maternal height, parity, sex and gestational age. Difference in mean birthweight between non-smokers in the lower and upper quintiles of cotinine was 0.2% (95% CI: -2.4, 2.8). Pooling the results of 10 studies plus our own gave an estimated difference in mean birthweight between women unexposed and exposed to passive smoke of 31 g (95% CI: 19, 44). CONCLUSIONS: Cotinine is a better predictor of birthweight than the reported number of cigarettes smoked. If biochemical analysis is impossible, then self-reported smoking habit should be obtained prospectively using a structured approach. Any effect on birthweight of maternal passive smoking during pregnancy is small compared with the effects of maternal active smoking.

Smoking, alcohol consumption, and leukocyte counts.

Blood was collected from 684 healthy volunteers and examined for total and differential white blood cell (WBC) counts. A subgroup also was tested for numbers of T cells, B cells, and CD4 and CD8 subsets. Smoking status and alcohol consumption were determined by means of questionnaire, and smoking status was verified with serum cotinine concentration. High smoking rate was associated with increases in all counts. Former smokers abstinent less than 5 years still demonstrated elevated counts, whereas those abstinent more than 5 years had WBC counts comparable to those in persons who were never smokers. Compared with levels in those who had never smoked, total WBC counts were 27% higher in current smokers and 14% higher in former smokers who were abstinent for less than 5 years. Lymphocyte counts were 9% higher in those consuming more than one alcoholic drink per day than in those consuming less alcohol, but drinking was not associated with other cell populations.

Does caffeine intake enhance absolute levels of cognitive performance?

The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of 9003 British adults (the Health and Lifestyle Survey). Subjects completed tests of simple reaction time, choice reaction time, incidental verbal memory, and visuo-spatial reasoning, in addition to providing self-reports of usual coffee and tea intake. After controlling extensively for potential confounding variables, a dose-response trend to improved performance with higher levels of coffee consumption was observed for all four tests (P < 0.001 in each case). Similar but weaker associations were found for tea consumption, which were significant for simple reaction time (P = 0.02) and visuo-spatial reasoning (P = 0.013). Estimated overall caffeine consumption showed a dose-response relationship to improved cognitive performance (P < 0.001 for each cognitive test, after controlling for confounders). Older people appeared to be more susceptible to the performance-improving effects of caffeine than were younger. The results suggest that tolerance to the performance-enhancing effects of caffeine, if it occurs at all, is incomplete.

The scientific case that nicotine is addictive.

Despite the wide-ranging and authoritative 1988 review by the US Surgeon General, views questioning the addictiveness of nicotine contine to be expressed in some quarters. This lack of complete consensus is not unexpected, since no universally agreed scientific definition of addiction exists. In this paper we briefly consider a number of lines of evidence from both the human and animal literature bearing on the addictiveness of nicotine. Patterns of use by smokers and the remarkable intractability of the smoking habit point to compulsive use as the norm. Studies in both animal and human subjects have shown that nicotine can function as reinforcer, albeit under a more limited range of conditions than with some other drugs of abuse. In drug discrimination paradigms there is some cross-generalisation between nicotine on the one hand, and amphetamine and cocaine on the other. A well-defined nicotine withdrawal syndrome has been delineated which is alleviated by nicotine replacement. Nicotine replacement also enhances outcomes in smoking cessation, roughly doubling success rates. In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine and alcohol.

Does switching to an ultra-low nicotine cigarette induce nicotine withdrawal effects?

Twenty-six smokers took part in a study which examined subjective and physiological effects of switching to an ultra-low yielding cigarette (0.1 mg nicotine) for 10 days. Subjects were randomly assigned to one of two groups. One group continued smoking their usual brand while the other group switched to the low yielding cigarette. Subjective ratings and physiological measures were taken at baseline, then after 1, 3 and 10 days in the respective conditions. Plasma nicotine concentrations dropped by some 60% after switching. Although substantial, this drop was considerably less than the drop in nominal yield of the cigarettes (around 90%), indicating marked compensation on the part of these smokers. Switching to the low yielding cigarette was accompanied by a significant increase in hunger and a drop in heart rate. These effects typically occur following cigarette withdrawal. However, other common cigarette withdrawal symptoms, such as irritability, depression, and inability to concentrate, were not detected.

Effect of smoke-free cigarettes on 24 h cigarette withdrawal: a double-blind placebo-controlled study.

In a double-blind randomised trial, 40 cigarette smokers used either nicotine-containing or placebo smoke-free cigarettes during 24 h abstinence from smoking. Subjects in the nicotine group experienced smaller increases in irritability and difficulty concentrating and fewer urges to smoke than those who received placebo. Nicotine smoke-free cigarettes were rated as more satisfying, more helpful and more effective in relieving craving than placebo. After 24 h use nicotine smoke-free cigarettes provided average blood nicotine levels of 6.3 ng/ml, i.e., 29.2% of smoking levels. The most frequent side effects were irritation of the throat and coughing. Overall, side effects were rated as not serious. Although the smoke-free cigarette in its present form is not very efficient in delivering nicotine, it was effective in alleviating initial tobacco withdrawal. It is possible that by providing both nicotine and "behavioural" replacement it may be particularly useful in the first stages of stopping smoking. The product is worth further investigation.

Nicotine intake and dependence in Swedish snuff takers.

Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products.

Non-smokers show acute tolerance to subcutaneous nicotine.

Plasma nicotine concentrations following subcutaneous (SC) injection were measured in six subjects who included three life-long nonsmokers. On average, a peak plasma level of 8.5 ng/ml (SD = 3.1) was reached 15 min after the mean dose of 13.25 micrograms/kg nicotine base. Subjective effects were reported by five subjects. The peak heart rate response (mean boost 11 beats per min at 10 min) preceded and was already declining by the time plasma nicotine concentrations peaked. Hysteresis plots showed clear evidence of acute nicotine tolerance in subjects who had never smoked, indicating that acute tolerance is not an acquired phenomenon. The acquisition by smokers of chronic tolerance to nicotine has not yet been systematically demonstrated. Reliable dose-response studies in smokers and nonsmokers are needed, and use of the SC route for this purpose is discussed.

Urinary adrenaline concentrations during 10 days of smoking abstinence.

Urinary adrenaline concentrations were measured in 17 subjects during 10 days of cigarette abstinence. Adrenaline concentrations dropped significantly in the first 3 days of cigarette withdrawal. This was followed by a significant rise. More subjects showed a U-shaped function of adrenaline over time than would be expected by chance. The evidence suggests that the drop in urinary adrenaline concentration following cigarette withdrawal does not merely constitute a return to a non-smoking state, but includes an element of rebound resulting from loss of a component of smoking, probably nicotine, to which adaptation has occurred.

Effect of subcutaneous nicotine injections of EEG alpha frequency in non-smokers: a placebo-controlled pilot study.

The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection and 8.5 ng/ml 10 min after the second injection. The nicotine injections produced an increase in mean dominant alpha frequency on the electroencephalogram (EEG) which was 2 Hz greater than the effect of placebo (P = 0.049) and also produced a heart-rate boost which was 8 beats per minute greater than that produced by placebo (P = 0.022). These effects on dominant alpha frequency and heart rate were most apparent in the 10 min following each nicotine injection. The increase in dominant alpha frequency found in non-smokers in this study was similar to that following nicotine inhalation in abstinent smokers in previous studies, and suggests that this is a primary effect of nicotine, rather than simply a reversal of withdrawal-induced EEG slowing.

A profile of tobacco smoking.

Cigarette smoking has for years been declining slowly in a number of major Western countries. It nevertheless remains highly prevalent, with one-quarter to one-third of adults being current smokers in the USA and Britain, and only some 40 per cent of those who have ever smoked cigarettes regularly have given up. Smoking is increasingly becoming a marker for deprivation and for a stressful life-style, and is also associated with consumption of other drugs. There is abundant and convincing evidence that, far from being confined to a minority of problem users, high levels of dependence on tobacco are experienced by a majority of smokers in the general population, with an onset early in the smoking career. The rewards which underpin continued smoking are unclear, but it may be that avoidance of the unpleasantness of not smoking is more significant than positively rewarding effects.

The association between having children, family size and smoking cessation in adults.

This study aimed to examine the relationship between rates of smoking cessation in adults and whether or not they have dependent children at home. Previous work has suggested that among women, particularly poor women, caring for young children might work against giving up smoking, while the relationship between having children and giving up smoking in men is largely unexplored. The analysis employed data from 3 years (1988, 1990 and 1992) of the General Household Survey, and assessed rates of self-reported smoking cessation among adult ever-smokers of cigarettes aged 16-49 years. After adjustment for a wide range of potential confounding variables, adults with dependent children were more likely to have given up smoking than those without. Among women there was a linear increase in the odds of cessation with each additional child. Using the combined data from the 3 years, and by comparison with those with no children, the adjusted odds of cessation were 1.42 (95% CI 1.21-1.67) in women with one dependent child, 1.77 (1.50-2.09) in those with two and 2.19 (1.74-2.74) in those with three or more. The effect was marginally present in men, with an increase in the odds of cessation of about 25% in those with two or more dependent children. (Estimated odds from the combined data 1.30 (1.09-1.50) for men with two dependent children and 1.23 (0.97-1.51) for those with three or more.) The association of increased rates of smoking cessation with number of dependent children did not vary with level of deprivation. It is concluded that having children is associated with smoking cessation in parents, whether poor or affluent. Health education campaigns targeted at families with children could aim to amplify this effect.