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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.


Background Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. Methods We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. Results At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04). Conclusions In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA-TIMI 61 number, NCT02019264 .).


To examine the cardiovascular risks of diclofenac initiation compared with initiation of other traditional non-steroidal anti-inflammatory drugs, initiation of paracetamol, and no initiation.


International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission.


Water ice may be allowed to accumulate in permanently shaded regions on airless bodies in the inner solar system such as Mercury, the Moon, and Ceres [Watson K, et al. (1961) J Geophys Res 66:3033-3045]. Unlike Mercury and Ceres, direct evidence for water ice exposed at the lunar surface has remained elusive. We utilize indirect lighting in regions of permanent shadow to report the detection of diagnostic near-infrared absorption features of water ice in reflectance spectra acquired by the Moon Mineralogy Mapper [M (3)] instrument. Several thousand M (3) pixels (∼280 × 280 m) with signatures of water ice at the optical surface (depth of less than a few millimeters) are identified within 20° latitude of both poles, including locations where independent measurements have suggested that water ice may be present. Most ice locations detected in M (3) data also exhibit lunar orbiter laser altimeter reflectance values and Lyman Alpha Mapping Project instrument UV ratio values consistent with the presence of water ice and also exhibit annual maximum temperatures below 110 K. However, only ∼3.5% of cold traps exhibit ice exposures. Spectral modeling shows that some ice-bearing pixels may contain ∼30 wt % ice that is intimately mixed with dry regolith. The patchy distribution and low abundance of lunar surface-exposed water ice might be associated with the true polar wander and impact gardening. The observation of spectral features of H2O confirms that water ice is trapped and accumulates in permanently shadowed regions of the Moon, and in some locations, it is exposed at the modern optical surface.


Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.


Background Diabetes mellitus is associated with an increased risk of cardiovascular events. Aspirin use reduces the risk of occlusive vascular events but increases the risk of bleeding; the balance of benefits and hazards for the prevention of first cardiovascular events in patients with diabetes is unclear. Methods We randomly assigned adults who had diabetes but no evident cardiovascular disease to receive aspirin at a dose of 100 mg daily or matching placebo. The primary efficacy outcome was the first serious vascular event (i.e., myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage). The primary safety outcome was the first major bleeding event (i.e., intracranial hemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other serious bleeding). Secondary outcomes included gastrointestinal tract cancer. Results A total of 15,480 participants underwent randomization. During a mean follow-up of 7.4 years, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.97; P=0.01). In contrast, major bleeding events occurred in 314 participants (4.1%) in the aspirin group, as compared with 245 (3.2%) in the placebo group (rate ratio, 1.29; 95% CI, 1.09 to 1.52; P=0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]); long-term follow-up for these outcomes is planned. Conclusions Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events. The absolute benefits were largely counterbalanced by the bleeding hazard. (Funded by the British Heart Foundation and others; ASCEND Current Controlled Trials number, ISRCTN60635500 ; number, NCT00135226 .).


Heat waves have profoundly impacted biota globally over the past decade, especially where their ecological impacts are rapid, diverse, and broad-scale. Although usually considered in isolation for either terrestrial or marine ecosystems, heat waves can straddle ecosystems of both types at subcontinental scales, potentially impacting larger areas and taxonomic breadth than previously envisioned. Using climatic and multi-species demographic data collected in Western Australia, we show that a massive heat wave event straddling terrestrial and maritime ecosystems triggered abrupt, synchronous, and multi-trophic ecological disruptions, including mortality, demographic shifts and altered species distributions. Tree die-off and coral bleaching occurred concurrently in response to the heat wave, and were accompanied by terrestrial plant mortality, seagrass and kelp loss, population crash of an endangered terrestrial bird species, plummeting breeding success in marine penguins, and outbreaks of terrestrial wood-boring insects. These multiple taxa and trophic-level impacts spanned >300,000 km2-comparable to the size of California-encompassing one terrestrial Global Biodiversity Hotspot and two marine World Heritage Areas. The subcontinental multi-taxa context documented here reveals that terrestrial and marine biotic responses to heat waves do not occur in isolation, implying that the extent of ecological vulnerability to projected increases in heat waves is underestimated.


To assess whether statin treatment is associated with a reduction in atherosclerotic cardiovascular disease (CVD) and mortality in old and very old adults with and without diabetes.


Migratory species often roam vast distances bringing them into contact with diverse conditions and threats that could play significant roles in their population dynamics. This is especially true if long-range travels occur within crucial stages of a species' annual life-cycle. Crested penguins, for example, usually disperse over several hundreds of kilometres after completing the energetically demanding breeding season and in preparation for the costly annual moult. A basic understanding of crested penguins' pre-moult dispersal is therefore paramount in order to be able to assess factors affecting individual survival. The Fiordland penguin, or Tawaki, the only crested penguin species breeding on the New Zealand mainland, is currently one of the least studied and rarest penguin species in the world. We successfully satellite tracked the pre-moult dispersal of 17 adult Tawaki from a single colony located in the species' northern breeding distribution. Over the course of 8-10 weeks the penguins travelled up to 2,500 km away from their breeding colony, covering total swimming distances of up to 6,800 km. During outbound travels all penguins headed south-west within a well-defined corridor before branching out towards two general trip destinations. Birds leaving in late November travelled towards the Subtropical Front some 800 km south of Tasmania, whereas penguins that left in December headed further towards the subantarctic front. Using K-select analysis we examined the influence of oceanographic factors on the penguins' dispersal. Water depth, surface current velocity and sea level anomalies had the greatest influence on penguin movements at the subantarctic Front, while sea surface temperature and chlorophyll a concentration were key for birds travelling to the subtropical front. We discuss our findings in the light of anthropogenic activities (or lack thereof) in the regions visited by the penguins as well as the potential consequences of Tawaki pre-moult dispersal for the species' breeding distribution on the New Zealand mainland.