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Food Is Medicine interventions are increasingly gaining attention from policy makers, payers, and health care professionals as a promising approach to addressing diet-related chronic health conditions in the health care setting, given the increasing burden and cost of these conditions. The American Heart Association defines Food Is Medicine as the provision of healthy food such as medically tailored meals, medically tailored groceries, and produce prescriptions to treat or manage specific clinical conditions in a way that is integrated with and paid for by the health care sector. Importantly, Food Is Medicine is distinct from, yet complementary to, food and nutrition assistance programs and population-level healthy food policies and programs. In this article, we discuss the importance of this distinction and the prerequisites for successfully integrating Food Is Medicine interventions within the health care system: a standard definition of Food Is Medicine focused on medically tailored meals, medically tailored groceries, and produce prescriptions; a research base showing clinical effectiveness and cost-effectiveness; and implementation that ensures fidelity and quality.

Knowledge of the size‐ and composition‐dependent production flux of primary sea spray aerosol (SSA) particles and its dependence on environmental variables is required for modeling cloud microphysical properties and aerosol radiative influences, interpreting measurements of particulate matter in coastal areas and its relation to air quality, and evaluating rates of uptake and reactions of gases in sea spray drops. This review examines recent research pertinent to SSA production flux, which deals mainly with production of particles with r80 (equilibrium radius at 80% relative humidity) less than 1 μm and as small as 0.01 μm. Production of sea spray particles and its dependence on controlling factors has been investigated in laboratory studies that have examined the dependences on water temperature, salinity, and the presence of organics and in field measurements with micrometeorological techniques that use newly developed fast optical particle sizers. Extensive measurements show that water‐insoluble organic matter contributes substantially to the composition of SSA particles with r80 < 0.25 μm and, in locations with high biological activity, can be the dominant constituent. Order‐of‐magnitude variation remains in estimates of the size‐dependent production flux per white area, the quantity central to formulations of the production flux based on the whitecap method. This variation indicates that the production flux may depend on quantities such as the volume flux of air bubbles to the surface that are not accounted for in current models. Variation in estimates of the whitecap fraction as a function of wind speed contributes additional, comparable uncertainty to production flux estimates.

Plant phenology regulates the carbon cycle and land‐atmosphere coupling. Currently, climate models often disagree with observations on the seasonal cycle of vegetation growth, partially due to how spring onset is measured and simulated. Here we use both thermal and leaf area index (LAI) based indicators to characterize spring onset in CMIP6 models. Although the historical timing varies considerably across models, most agree that spring has advanced in recent decades and will continue to arrive earlier with future warming. Across the Northern Hemisphere for the periods 1950–2014, 1981–2014, and 2015–2099 in the historical and SSP5‐8.5 simulations, thermal‐based indicators estimate spring advances of −0.7 ± 0.2, −1.4 ± 0.4, and −2.4 ± 0.7 days/decade, while LAI‐based indicators estimate −0.4 ± 0.3, −0.1 ± 0.3, and −1±1.1 days/decade. Thereby, LAI‐based indicators exhibit weaker trends toward earlier onset, leading to uncertainties from different indices being as large or larger than model uncertainty. Reconciling these discrepancies is critical for understanding future changes in spring onset. Plain Language Summary The timing of spring onset as indicated by green‐up affects plants, bird and insect populations, rivers, and agriculture. However, state‐of‐the‐art land surface models disagree with satellite‐derived records on the seasonal cycles of vegetation growth, making it difficult to accurately predict green‐up, its response to climate, and the ecological consequences. Here we calculate two sets of spring onset indicators using climate model outputs to characterize spring onset variations and trends in the recent past and future. We find spring has been advancing in recent decades and will continue to arrive earlier with future warming. Thermal‐based indicators show that spring onset advances by −0.7, −1.4, and −2.4 days/decade in the Northern Hemisphere during 1950–2014, 1981–2014, and 2015–2099, respectively. This result suggests that spring onset today is on average four days earlier than spring onset 30 years ago and this rate will nearly double in the future. However, compared to meteorological‐based indicators, vegetation growth‐based indicators exhibit weaker trends toward earlier onset. Therefore, how we define and measure spring onset, as well as the models we use to predict changes in the environmental factors, influence future changes in the start of spring. Key Points Divergence between thermal‐ and growth‐based spring onset indicators grows with time as global temperatures increase Thermal‐based indicators estimate spring advances of −0.7, −1.4, and −2.4 days/decade in 1950–2014, 1981–2014, and 2015–2099 Vegetation growth‐based indicators exhibit weaker trends toward earlier spring onset and larger disagreements among models

Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics 1 – 4 . The All of Us Research Program is a longitudinal cohort study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health 5 , 6 . Here we describe the programme’s genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are individuals from under-represented racial and ethnic minorities. All of Us identified more than 1 billion genetic variants, including more than 275 million previously unreported genetic variants, more than 3.9 million of which had coding consequences. Leveraging linkage between genomic data and the longitudinal electronic health record, we evaluated 3,724 genetic variants associated with 117 diseases and found high replication rates across both participants of European ancestry and participants of African ancestry. Summary-level data are publicly available, and individual-level data can be accessed by researchers through the All of Us Researcher Workbench using a unique data passport model with a median time from initial researcher registration to data access of 29 hours. We anticipate that this diverse dataset will advance the promise of genomic medicine for all. A study describes the release of clinical-grade whole-genome sequence data for 245,388 diverse participants by the All of Us Research Program and characterizes the properties of the dataset.

Fossil hominins from South Africa are enriching the story of early human evolution and dispersal. Herries et al. describe the geological context and dating of the hominin-bearing infilled cave, or palaeocave, at a site called Drimolen in South Africa (see the Perspective by Antón). They focus on the age and context of a recently discovered Homo erectus sensu lato fossil and a Paranthropus robustus fossil, which they dated to ∼2.04 million to 1.95 million years ago. This makes Drimolen one of the best-dated sites in South Africa and establishes these fossils as the oldest definitive specimens of their respective species ever discovered. The age confirms that species of Australopithecus, Paranthropus , and early Homo overlapped in the karst of South Africa ∼2 million years ago. Science , this issue p. eaaw7293 ; see also p. 34 Multiple hominin genera, including the earliest Homo erectus lineage, were present in South Africa 2 million years ago. Understanding the extinction of Australopithecus and origins of Paranthropus and Homo in South Africa has been hampered by the perceived complex geological context of hominin fossils, poor chronological resolution, and a lack of well-preserved early Homo specimens. We describe, date, and contextualize the discovery of two hominin crania from Drimolen Main Quarry in South Africa. At ~2.04 million to 1.95 million years old, DNH 152 represents the earliest definitive occurrence of Paranthropus robustus , and DNH 134 represents the earliest occurrence of a cranium with clear affinities to Homo erectus . These crania also show that Homo , Paranthropus , and Australopithecus were contemporaneous at ~2 million years ago. This high taxonomic diversity is also reflected in non-hominin species and provides evidence of endemic evolution and dispersal during a period of climatic variability.

Inactivating mutations in NPC1L1 were identified on exon sequencing and genotyping in 16 cohorts of patients with coronary heart disease and controls. Mutation carriers had lower LDL cholesterol levels and a lower risk of coronary heart disease than did noncarriers. Ezetimibe, a drug that is commonly prescribed to reduce plasma levels of low-density lipoprotein (LDL) cholesterol, inhibits the function of the protein encoded by the Niemann–Pick C1-like 1 gene ( NPC1L1 ). 1 NPC1L1 protein, which is expressed in the small intestine and liver, functions as a transporter of dietary cholesterol from the gut lumen into intestinal enterocytes. 2 , 3 Because of its ability to block sterol absorption by about 50%, 4 ezetimibe lowers plasma LDL cholesterol levels by 15 to 20%. 5 However, it is uncertain whether inhibiting NPC1L1 — either through ezetimibe treatment or by other means — reduces the risk of . . .

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection 1 , 2 , yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases. A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

Thromboembolic events after total joint arthroplasty are potentially devastating complications. This study evaluated the efficacy of 4 different anticoagulants in preventing deep venous thrombosis and pulmonary embolism after total joint arthroplasty. The demographics and anticoagulant use (warfarin, enoxaparin, and aspirin with and without outpatient mechanical pumps) for patients who underwent primary unilateral total joint arthroplasties performed by a single surgeon from January 2013 to October 2014 were retrospectively reviewed. All patients underwent lower extremity ultrasound at the 3-week postoperative visit. A total of 613 primary unilateral total joint arthroplasties met the study inclusion criteria. There were 288 primary total knee arthroplasties and 325 primary total hip arthroplasties. The patients were 62.2% female, having a mean age of 67.6±10.6 years and a mean body mass index of 30.2±5.9 kg/m 2 . There were 119 patients in group 1 (aspirin alone), 40 patients in group 2 (aspirin plus pumps), 246 patients in group 3 (warfarin), and 208 patients in group 4 (enoxaparin). The overall 3-week symptomatic and asymptomatic deep venous thrombosis and symptomatic pulmonary embolism rates in the entire cohort were 5.7% and 0.3%, respectively. The venous thromboembolism rate was significantly affected by the anticoagulant of choice ( P <.01). Compared with aspirin alone, warfarin decreased the risk of venous thromboembolism ( P <.01). Increasing age led to increased risk of venous thromboembolism ( P =.05). This study indicated that aspirin chemoprophylaxis alone was not as efficacious as warfarin and enoxaparin in preventing asymptomatic and symptomatic venous thromboembolism found during routine postoperative surveillance with lower extremity ultrasound. Aspirin alone may be inadequate and should be augmented with an outpatient mechanical pump as part of multimodal prophylaxis. [ Orthopedics . 2019; 42(1):48–55.]