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3019

Background Quantifying the effect of natural disasters on society is critical for recovery of public health services and infrastructure. The death toll can be difficult to assess in the aftermath of a major disaster. In September 2017, Hurricane Maria caused massive infrastructural damage to Puerto Rico, but its effect on mortality remains contentious. The official death count is 64. Methods Using a representative, stratified sample, we surveyed 3299 randomly chosen households across Puerto Rico to produce an independent estimate of all-cause mortality after the hurricane. Respondents were asked about displacement, infrastructure loss, and causes of death. We calculated excess deaths by comparing our estimated post-hurricane mortality rate with official rates for the same period in 2016. Results From the survey data, we estimated a mortality rate of 14.3 deaths (95% confidence interval [CI], 9.8 to 18.9) per 1000 persons from September 20 through December 31, 2017. This rate yielded a total of 4645 excess deaths during this period (95% CI, 793 to 8498), equivalent to a 62% increase in the mortality rate as compared with the same period in 2016. However, this number is likely to be an underestimate because of survivor bias. The mortality rate remained high through the end of December 2017, and one third of the deaths were attributed to delayed or interrupted health care. Hurricane-related migration was substantial. Conclusions This household-based survey suggests that the number of excess deaths related to Hurricane Maria in Puerto Rico is more than 70 times the official estimate. (Funded by the Harvard T.H. Chan School of Public Health and others.).

2328

This paper focuses on an overview of radioactive cesium 137 (quasi-Cs137 included Cs134) contamination of freshwater fish in Fukushima and eastern Japan based on the data published by the Fisheries Agency of the Japanese Government in 2011. In the area north and west of the Fukushima Nuclear plant, freshwater fish have been highly contaminated. For example, the mean of active cesium (quasi-Cs137) contamination of Ayu (Plecoglossus altivelis) is 2,657 Bq/kg at Mano River, 20-40 km north-west from the plant. Bioaccumulation is observed in the Agano river basin in Aizu sub-region, 70-150 km west from the plant. The active cesium (quasi-Cs137) contamination of carnivorous Salmondae is around 2 times higher than herbivorous Ayu. The extent of active cesium (quasi-Cs137) contamination of Ayu is observed in the entire eastern Japan. The some level of the contamination is recognized even in Shizuoka prefecture, 400 km south-west from the plant.

Concepts: Chernobyl disaster, Japan, Freshwater fish, Prefectures of Japan, Government of Japan, Honshū, Shizuoka Prefecture, Ayu

1618

Despite efforts to recruit and retain more women, a stark gender disparity persists within academic science. Abundant research has demonstrated gender bias in many demographic groups, but has yet to experimentally investigate whether science faculty exhibit a bias against female students that could contribute to the gender disparity in academic science. In a randomized double-blind study (n = 127), science faculty from research-intensive universities rated the application materials of a student-who was randomly assigned either a male or female name-for a laboratory manager position. Faculty participants rated the male applicant as significantly more competent and hireable than the (identical) female applicant. These participants also selected a higher starting salary and offered more career mentoring to the male applicant. The gender of the faculty participants did not affect responses, such that female and male faculty were equally likely to exhibit bias against the female student. Mediation analyses indicated that the female student was less likely to be hired because she was viewed as less competent. We also assessed faculty participants' preexisting subtle bias against women using a standard instrument and found that preexisting subtle bias against women played a moderating role, such that subtle bias against women was associated with less support for the female student, but was unrelated to reactions to the male student. These results suggest that interventions addressing faculty gender bias might advance the goal of increasing the participation of women in science.

Concepts: Scientific method, Female, Gender, University, Gender role, Experiment, Woman, Bias

1550

We explore the risk that self-reinforcing feedbacks could push the Earth System toward a planetary threshold that, if crossed, could prevent stabilization of the climate at intermediate temperature rises and cause continued warming on a “Hothouse Earth” pathway even as human emissions are reduced. Crossing the threshold would lead to a much higher global average temperature than any interglacial in the past 1.2 million years and to sea levels significantly higher than at any time in the Holocene. We examine the evidence that such a threshold might exist and where it might be. If the threshold is crossed, the resulting trajectory would likely cause serious disruptions to ecosystems, society, and economies. Collective human action is required to steer the Earth System away from a potential threshold and stabilize it in a habitable interglacial-like state. Such action entails stewardship of the entire Earth System-biosphere, climate, and societies-and could include decarbonization of the global economy, enhancement of biosphere carbon sinks, behavioral changes, technological innovations, new governance arrangements, and transformed social values.

1517

Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

Concepts: Pharmacology, Clinical trial, Drug discovery, Medicinal chemistry, Natural product, High-throughput screening, Natural products

1515

Global declines in insects have sparked wide interest among scientists, politicians, and the general public. Loss of insect diversity and abundance is expected to provoke cascading effects on food webs and to jeopardize ecosystem services. Our understanding of the extent and underlying causes of this decline is based on the abundance of single species or taxonomic groups only, rather than changes in insect biomass which is more relevant for ecological functioning. Here, we used a standardized protocol to measure total insect biomass using Malaise traps, deployed over 27 years in 63 nature protection areas in Germany (96 unique location-year combinations) to infer on the status and trend of local entomofauna. Our analysis estimates a seasonal decline of 76%, and mid-summer decline of 82% in flying insect biomass over the 27 years of study. We show that this decline is apparent regardless of habitat type, while changes in weather, land use, and habitat characteristics cannot explain this overall decline. This yet unrecognized loss of insect biomass must be taken into account in evaluating declines in abundance of species depending on insects as a food source, and ecosystem functioning in the European landscape.

Concepts: Biodiversity, Insect, Ecology, Crustacean, Ecosystem, Taxonomic rank, Ant, Ecological economics

1504

Background Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. Methods In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. Results A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. Conclusions Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government’s Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639 .).

Concepts: Myocardial infarction, Atherosclerosis, Cardiovascular disease, Low-density lipoprotein, Fat, Olive oil, Greece, Mediterranean diet

1488

Objective To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective population based study. Setting UK Biobank.Participants 263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode v non-active (car or public transport)) to commute to and from work on a typical day.Main outcome measures Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes.Results 2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes.Conclusions Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions.

Concepts: Epidemiology, Disease, Statistics, Death, Median, Sustainable transport, Bicycle, Commuting

1461

Ocean plastic can persist in sea surface waters, eventually accumulating in remote areas of the world’s oceans. Here we characterise and quantify a major ocean plastic accumulation zone formed in subtropical waters between California and Hawaii: The Great Pacific Garbage Patch (GPGP). Our model, calibrated with data from multi-vessel and aircraft surveys, predicted at least 79 (45-129) thousand tonnes of ocean plastic are floating inside an area of 1.6 million km2; a figure four to sixteen times higher than previously reported. We explain this difference through the use of more robust methods to quantify larger debris. Over three-quarters of the GPGP mass was carried by debris larger than 5 cm and at least 46% was comprised of fishing nets. Microplastics accounted for 8% of the total mass but 94% of the estimated 1.8 (1.1-3.6) trillion pieces floating in the area. Plastic collected during our study has specific characteristics such as small surface-to-volume ratio, indicating that only certain types of debris have the capacity to persist and accumulate at the surface of the GPGP. Finally, our results suggest that ocean plastic pollution within the GPGP is increasing exponentially and at a faster rate than in surrounding waters.

Concepts: Great Pacific Garbage Patch, Pacific Ocean, Ocean, Marine pollution, North Pacific Gyre, Project Kaisei

1414

Low carbohydrate diets, which restrict carbohydrate in favour of increased protein or fat intake, or both, are a popular weight-loss strategy. However, the long-term effect of carbohydrate restriction on mortality is controversial and could depend on whether dietary carbohydrate is replaced by plant-based or animal-based fat and protein. We aimed to investigate the association between carbohydrate intake and mortality.