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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.).


Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.

Concepts: Cancer, Biology, Lymph node, Liver, Histology, Lymphatic system, Anatomy, Human anatomy


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


A census of the biomass on Earth is key for understanding the structure and dynamics of the biosphere. However, a global, quantitative view of how the biomass of different taxa compare with one another is still lacking. Here, we assemble the overall biomass composition of the biosphere, establishing a census of the ≈550 gigatons of carbon (Gt C) of biomass distributed among all of the kingdoms of life. We find that the kingdoms of life concentrate at different locations on the planet; plants (≈450 Gt C, the dominant kingdom) are primarily terrestrial, whereas animals (≈2 Gt C) are mainly marine, and bacteria (≈70 Gt C) and archaea (≈7 Gt C) are predominantly located in deep subsurface environments. We show that terrestrial biomass is about two orders of magnitude higher than marine biomass and estimate a total of ≈6 Gt C of marine biota, doubling the previous estimated quantity. Our analysis reveals that the global marine biomass pyramid contains more consumers than producers, thus increasing the scope of previous observations on inverse food pyramids. Finally, we highlight that the mass of humans is an order of magnitude higher than that of all wild mammals combined and report the historical impact of humanity on the global biomass of prominent taxa, including mammals, fish, and plants.


Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes (COL1A1,COL2A1,KMT2D,FLNB,ATR,TRIP11,PCNT) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata’s peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification.

Concepts: DNA, Gene, Genetics, Mutation, Evolution, Molecular biology, Human genome, Chile


Despite concerted international effort to track and interpret shifts in the abundance and distribution of Adélie penguins, large populations continue to be identified. Here we report on a major hotspot of Adélie penguin abundance identified in the Danger Islands off the northern tip of the Antarctic Peninsula (AP). We present the first complete census of Pygoscelis spp. penguins in the Danger Islands, estimated from a multi-modal survey consisting of direct ground counts and computer-automated counts of unmanned aerial vehicle (UAV) imagery. Our survey reveals that the Danger Islands host 751,527 pairs of Adélie penguins, more than the rest of AP region combined, and include the third and fourth largest Adélie penguin colonies in the world. Our results validate the use of Landsat medium-resolution satellite imagery for the detection of new or unknown penguin colonies and highlight the utility of combining satellite imagery with ground and UAV surveys. The Danger Islands appear to have avoided recent declines documented on the Western AP and, because they are large and likely to remain an important hotspot for avian abundance under projected climate change, deserve special consideration in the negotiation and design of Marine Protected Areas in the region.

Concepts: Climate change, Seabird, Penguin, Remote sensing, Antarctica, Aerial photography, Unmanned aerial vehicle, Unmanned vehicles


Background The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. Methods We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). Results Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. Conclusions Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx number, NCT00310180 .).


Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 Å resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral α/β-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.

Concepts: DNA, Protein, Evolution, Amino acid, Crystal, Polymer, Materials science, Polyester


The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.


To examine the associations between egg consumption and cardiovascular disease (CVD), ischaemic heart disease (IHD), major coronary events (MCE), haemorrhagic stroke as well as ischaemic stroke.