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Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods, and the extent of the reduction in risk when cigarette smoking is stopped at different ages. Design Prospective study that has continued from 1951 to 2001. Setting United Kingdom. Participants 34 439 male British doctors. Information about their smoking habits was obtained in 1951, and periodically thereafter; cause specific mortality was monitored for 50 years. Main outcome measures Overall mortality by smoking habit, considering separately men born in different periods. Results The excess mortality associated with smoking chiefly involved vascular, neoplastic, and respiratory diseases that can be caused by smoking. Men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers. Cessation at age 60, 50, 40, or 30 years gained, respectively, about 3, 6, 9, or 10 years of life expectancy. The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s. The cigarette smoker versus non-smoker probabilities of dying in middle age (35-69) were 42% ν24% (a twofold death rate ratio) for those born in 1900-1909, but were 43% ν 15% (a threefold death rate ratio) for those born in the 1920s. At older ages, the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10% ν 12% at the death rates of the 1950s (that is, among men born around the 1870s) but were 7% ν 33% (again a threefold death rate ratio) at the death rates of the 1990s (that is, among men born around the 1910s). Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century (due to prevention and improved treatment of disease) has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes. Among the men born around 1920, prolonged cigarette smoking from early adult life tripled age specific mortality rates, but cessation at age 50 halved the hazard, and cessation at age 30 avoided almost all of it.

Abstract Objective: To assess the hazards associated with long term use of tobacco. Design: Prospective study of mortality in relation to smoking habits assessed in 1951 and again from20time to time thereafter, with causes sought of deaths20over 40 years (to 1991). Continuation of a study that was last reported after 20 years' follow up (1951-71). Subjects: 34 439 British male doctors who replied20to a postal questionnaire in 1951, of whom 10 000 had died during the first 20 years and another 10 000 have died during the second 20 years. Results - Excess mortality associated with20smoking was about twice as extreme during the second half of the study as it had been during the first half. The death rate ratios during 1971-91 (comparing continuing cigarette smokers with lifelong20non-smokers) were approximately threefold at ages 45-64 and twofold at ages 65-84. The excess mortality was chiefly from diseases that can be caused by smoking. Positive associations with smoking were confirmed for death from cancers of the mouth, oesophagus, pharynx, larynx, lung, pancreas, and bladder; from chronic obstructive pulmonary disease and other respiratory diseases; from vascular diseases; from peptic ulcer; and (perhaps because of confounding by personality and alcohol use) from cirrhosis, suicide, and poisoning. A negative association was confirmed with death20from Parkinson's disease. Those who stopped20smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered, but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke. Conclusion: Results from the first 20 years of this study, and of other studies at that time, substantially20underestimated the hazards of long term use of tobacco. It now seems that about half of all regular cigarette smokers will eventually be killed by their habit.

Abstract Objective: To assess the possible association between smoking and dementia. Design: Prospective study. Setting: Cohort of British male doctors followed up since 1951. Subjects: 34 439 male British doctors, with 24 133 deaths recorded. Results: For all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer's disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer's disease in particular. Conclusions: Contrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer's disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.

Conclusion: A substantial progressive decrease in the mortality rates among non-smokers over the past half century (due to prevention and improved treatment of disease) has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker v non-smoker death rate ratio due to earlier and more intensive use of cigarettes.

The ocean provides food, economic activity, and cultural value for a large proportion of humanity. Our knowledge of marine ecosystems lags behind that of terrestrial ecosystems, limiting effective protection of marine resources. We describe the outcome of 2 workshops in 2011 and 2012 to establish a list of important questions, which, if answered, would substantially improve our ability to conserve and manage the world's marine resources. Participants included individuals from academia, government, and nongovernment organizations with broad experience across disciplines, marine ecosystems, and countries that vary in levels of development. Contributors from the fields of science, conservation, industry, and government submitted questions to our workshops, which we distilled into a list of priority research questions. Through this process, we identified 71 key questions. We grouped these into 8 subject categories, each pertaining to a broad component of marine conservation: fisheries, climate change, other anthropogenic threats, ecosystems, marine citizenship, policy, societal and cultural considerations, and scientific enterprise. Our questions address many issues that are specific to marine conservation, and will serve as a road map to funders and researchers to develop programs that can greatly benefit marine conservation. Setenta y Un Preguntas Importantes para la Conservación de la Biodiversidad Marina

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes. Naturally acquired antibodies may inhibit Plasmodium survival in mosquitoes, alter malaria transmission dynamics, and form the basis for transmission-blocking vaccines. Here, using sera from malaria-exposed individuals, Stone et al. reveal novel antibody correlates of transmission-reducing activity.

In the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes. WE COMPARED TWO COMMONLY USED MOSQUITO FEEDING ASSAY PROCEDURES: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum. 930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94-2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p<0.0001). Replacing the plasma of the gametocyte donor with malaria naïve control serum resulted in higher mosquito infection rates compared to own plasma (OR 1.92, 95% CI 1.68-2.19) while the infectiousness of gametocytes may be reduced during the replacement procedure (OR 0.60, 95% CI 0.52-0.70). Despite a higher efficiency of direct skin feeding assays, membrane feeding assays appear suitable tools to compare the infectiousness between individuals and to evaluate transmission-reducing interventions. Several aspects of membrane feeding procedures currently lack standardization; this variability makes comparisons between laboratories challenging and should be addressed to facilitate future testing of transmission-reducing interventions.

The biodiversity of marine and coastal habitats is experiencing unprecedented change. While there are well-known drivers of these changes, such as overexploitation, climate change and pollution, there are also relatively unknown emerging issues that are poorly understood or recognized that have potentially positive or negative impacts on marine and coastal ecosystems. In this inaugural Marine and Coastal Horizon Scan, we brought together 30 scientists, policymakers and practitioners with transdisciplinary expertise in marine and coastal systems to identify new issues that are likely to have a significant impact on the functioning and conservation of marine and coastal biodiversity over the next 5–10 years. Based on a modified Delphi voting process, the final 15 issues presented were distilled from a list of 75 submitted by participants at the start of the process. These issues are grouped into three categories: ecosystem impacts, for example the impact of wildfires and the effect of poleward migration on equatorial biodiversity; resource exploitation, including an increase in the trade of fish swim bladders and increased exploitation of marine collagens; and new technologies, such as soft robotics and new biodegradable products. Our early identification of these issues and their potential impacts on marine and coastal biodiversity will support scientists, conservationists, resource managers and policymakers to address the challenges facing marine ecosystems. A panel of scientists, policymakers and practitioners have used an iterative voting process to collate a list of 15 priority emerging issues likely to affect marine and coastal biodiversity over the next 5–10 years.

Background People with opioid use disorder (OUD) are high-risk for short-term mortality and morbidity. Emergency department (ED) interventions can reduce those risks, but benefits wane without ongoing community follow-up. Objective To evaluate an ED-based intensive community outreach program. Methods At two urban EDs between October 2019 and March 2020, we enrolled patients with OUD not currently on opioid agonist therapy (OAT) in a prospective cohort study evaluating a one-year intensive community outreach program, which provided ongoing addictions care, housing resources, and community support. We surveyed patients at intake and at scheduled outreach encounters at one, two, six, and twelve months. Follow-up surveys assessed OAT uptake, addictions care engagement, housing status, quality of life scores, illicit opioid use, and outreach helpfulness. We used descriptive statistics for each period and conducted sensitivity and subgroup analyses to account for missing data. Results Of 84 baseline participants, 29% were female and 32% were housed, with a median age of 33. Sixty participants (71%) completed at least one follow-up survey. Survey completion rates were 37%, 38%, 39%, and 40% respectively at one, two, six, and twelve months. Participants had a median of three outreach encounters. Among respondents, OAT was 0% at enrolment and ranged from 38% to 56% at follow-up; addictions care engagement was 22% at enrolment and ranged from 65% to 81% during follow-up; and housing was 40% at enrolment and ranged from 48% to 59% during follow-up. Improvements from baseline to follow-up occurred for all time periods. OAT and engagement in care benefits were maintained in sensitivity and subgroup analyses. Respondents rated the outreach program as helpful at all time periods, Conclusion An ED-initiated intensive outreach program for patients with OUD not yet on OAT was associated with a persistent increase in OAT use and engagement in care, as well as housing.