IMPORTANCE: US health care spending has continued to increase and now accounts for 18% of the US economy, although little is known about how spending on each health condition varies by payer, and how ...these amounts have changed over time. OBJECTIVE: To estimate US spending on health care according to 3 types of payers (public insurance including Medicare, Medicaid, and other government programs, private insurance, or out-of-pocket payments) and by health condition, age group, sex, and type of care for 1996 through 2016. DESIGN AND SETTING: Government budgets, insurance claims, facility records, household surveys, and official US records from 1996 through 2016 were collected to estimate spending for 154 health conditions. Spending growth rates (standardized by population size and age group) were calculated for each type of payer and health condition. EXPOSURES: Ambulatory care, inpatient care, nursing care facility stay, emergency department care, dental care, and purchase of prescribed pharmaceuticals in a retail setting. MAIN OUTCOMES AND MEASURES: National spending estimates stratified by health condition, age group, sex, type of care, and type of payer and modeled for each year from 1996 through 2016. RESULTS: Total health care spending increased from an estimated $1.4 trillion in 1996 (13.3% of gross domestic product GDP; $5259 per person) to an estimated $3.1 trillion in 2016 (17.9% of GDP; $9655 per person); 85.2% of that spending was included in this study. In 2016, an estimated 48.0% (95% CI, 48.0%-48.0%) of health care spending was paid by private insurance, 42.6% (95% CI, 42.5%-42.6%) by public insurance, and 9.4% (95% CI, 9.4%-9.4%) by out-of-pocket payments. In 2016, among the 154 conditions, low back and neck pain had the highest amount of health care spending with an estimated $134.5 billion (95% CI, $122.4-$146.9 billion) in spending, of which 57.2% (95% CI, 52.2%-61.2%) was paid by private insurance, 33.7% (95% CI, 30.0%-38.4%) by public insurance, and 9.2% (95% CI, 8.3%-10.4%) by out-of-pocket payments. Other musculoskeletal disorders accounted for the second highest amount of health care spending (estimated at $129.8 billion 95% CI, $116.3-$149.7 billion) and most had private insurance (56.4% 95% CI, 52.6%-59.3%). Diabetes accounted for the third highest amount of the health care spending (estimated at $111.2 billion 95% CI, $105.7-$115.9 billion) and most had public insurance (49.8% 95% CI, 44.4%-56.0%). Other conditions estimated to have substantial health care spending in 2016 were ischemic heart disease ($89.3 billion 95% CI, $81.1-$95.5 billion), falls ($87.4 billion 95% CI, $75.0-$100.1 billion), urinary diseases ($86.0 billion 95% CI, $76.3-$95.9 billion), skin and subcutaneous diseases ($85.0 billion 95% CI, $80.5-$90.2 billion), osteoarthritis ($80.0 billion 95% CI, $72.2-$86.1 billion), dementias ($79.2 billion 95% CI, $67.6-$90.8 billion), and hypertension ($79.0 billion 95% CI, $72.6-$86.8 billion). The conditions with the highest spending varied by type of payer, age, sex, type of care, and year. After adjusting for changes in inflation, population size, and age groups, public insurance spending was estimated to have increased at an annualized rate of 2.9% (95% CI, 2.9%-2.9%); private insurance, 2.6% (95% CI, 2.6%-2.6%); and out-of-pocket payments, 1.1% (95% CI, 1.0%-1.1%). CONCLUSIONS AND RELEVANCE: Estimates of US spending on health care showed substantial increases from 1996 through 2016, with the highest increases in population-adjusted spending by public insurance. Although spending on low back and neck pain, other musculoskeletal disorders, and diabetes accounted for the highest amounts of spending, the payers and the rates of change in annual spending growth rates varied considerably.
A process‐based treatment of ice supersaturation and ice nucleation is implemented in the National Center for Atmospheric Research Community Atmosphere Model (CAM). The new scheme is designed to ...allow (1) supersaturation with respect to ice, (2) ice nucleation by aerosol particles, and (3) ice cloud cover consistent with ice microphysics. The scheme is implemented with a two‐moment microphysics code and is used to evaluate ice cloud nucleation mechanisms and supersaturation in CAM. The new model is able to reproduce field observations of ice mass and mixed phase cloud occurrence better than previous versions. The model is able to reproduce observed patterns and frequency of ice supersaturation. Simulations indicate homogeneous freezing of sulfate and heterogeneous freezing on dust are both important ice nucleation mechanisms, in different regions. Simulated cloud forcing and climate is sensitive to different formulations of the ice microphysics. Arctic surface radiative fluxes are sensitive to the parameterization of ice clouds. These results indicate that ice clouds are potentially an important part of understanding cloud forcing and potential cloud feedbacks, particularly in the Arctic.
Gastroesophageal adenocarcinomas (GEAs) are heterogeneous cancers where immune checkpoint inhibitors have robust efficacy in heavily inflamed microsatellite instability (MSI) or Epstein-Barr virus ...(EBV)-positive subtypes. Immune checkpoint inhibitor responses are markedly lower in diffuse/genome stable (GS) and chromosomal instable (CIN) GEAs. In contrast to EBV and MSI subtypes, the tumor microenvironment of CIN and GS GEAs have not been fully characterized to date, which limits our ability to improve immunotherapeutic strategies.
Here we aimed to identify tumor-immune cell association across GEA subclasses using data from The Cancer Genome Atlas (N = 453 GEAs) and archival GEA resection specimen (N = 71). The Cancer Genome Atlas RNAseq data were used for computational inferences of immune cell subsets, which were correlated to tumor characteristics within and between subtypes. Archival tissues were used for more spatial immune characterization spanning immunohistochemistry and mRNA expression analyses.
Our results confirmed substantial heterogeneity in the tumor microenvironment between distinct subtypes. While MSI-high and EBV+ GEAs harbored most intense T cell infiltrates, the GS group showed enrichment of CD4+ T cells, macrophages and B cells and, in ∼50% of cases, evidence for tertiary lymphoid structures. In contrast, CIN cancers possessed CD8+ T cells predominantly at the invasive margin while tumor-associated macrophages showed tumor infiltrating capacity. Relatively T cell-rich ‘hot’ CIN GEAs were often from Western patients, while immunological ‘cold’ CIN GEAs showed enrichment of MYC and cell cycle pathways, including amplification of CCNE1.
These results reveal the diversity of immune phenotypes of GEA. Half of GS gastric cancers have tertiary lymphoid structures and are therefore promising candidates for immunotherapy. The majority of CIN GEAs, however, exhibit T cell exclusion and infiltrating macrophages. Associations of immune-poor CIN GEAs with MYC activity and CCNE1 amplification may enable new studies to determine precise mechanisms of immune evasion, ultimately inspiring new therapeutic modalities.
•There is large heterogeneity in the immune contexture of gastroesophageal adenocarcinoma (GEA) subtypes.•Chromosomal instable GEAs are often T cell excluded, which is associated with enhanced MYC and cell cycle pathways.•Genome stable cancers, contrarily, often have tertiary lymphoid structures.•This study argues for more personalized immunotargeting strategies in gastroesophageal cancer treatment.
Public health is a priority for the Chinese Government. Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount ...importance. This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level.
We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017. We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk. We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI).
Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017. Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval UI 29·8 to 37·4) for stroke and increased by 4·6% (–3·3 to 10·7) for ischaemic heart disease from 1990 to 2017. Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017. Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs. All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88. The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain. The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4).
China has made substantial progress in reducing the burden of many diseases and disabilities. Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system.
China National Key Research and Development Program and Bill & Melinda Gates Foundation.
Background and aims
Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative ...reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells.
Methods
The stability of mast cell lines, HMC1 cells, RBL‐2H3 cells, p815 cells, and mouse bone marrow‐derived mast cells (BMMC) was tested in the presence or absence of VitD3.
Results
Mast cells activated automatically in a VitD‐deficient environment. Exposure to calcitriol in the culture increased the expression of VitD receptor (VDR) in mast cells. VDR formed complexes with Lyn in mast cells to inhibit the binding of Lyn to the β chain of FcεRI and MyD88, which decreased the phosphorylation of Syk, decreased the levels of MAPK and NF‐κB. VDR bound to the promoter of TNF‐α to decrease the acetylation of histone H3/H4, RNA polymerase II and OCT1 (a transcription factor of TNF‐α) at the promoter locus and repressed the expression of TNF‐α in mast cells.
Conclusions
The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.
A consequent tendency toward high-performance quantum information processing is to develop the fully integrated photonic chip. Here, we report the on-chip generation and manipulation of entangled ...photons based on reconfigurable lithium-niobate waveguide circuits. By introducing a periodically poled structure into the waveguide circuits, two individual photon-pair sources with a controllable electro-optic phase shift are produced within a Hong-Ou-Mandel interferometer, resulting in a deterministically separated identical photon pair. The state is characterized by 92.9±0.9% visibility Hong-Ou-Mandel interference. The photon flux reaches ∼1.4×10(7) pairs nm-1 mW-1. The whole chip is designed to contain nine similar units to produce identical photon pairs spanning the telecom C and L band by the flexible engineering of nonlinearity. Our work presents a scenario for on-chip engineering of different photon sources and paves the way to fully integrated quantum technologies.
Background: There is some evidence for an association between traffic noise and ischemic heart disease; however, associations with blood pressure have been inconsistent, and little is known about ...health effects of railway noise. Objectives: We aimed to investigate the effects of railway and traffic noise exposure on blood pressure; a secondary aim was to address potentially susceptible subpopulations. Methods: We performed adjusted linear regression analyses using data from 6,450 participants of the second survey of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA 2) to estimate the associations of daytime and nighttime railway and traffic noise (A-weighted decibels) with systolic blood pressure (SBP) and diastolic blood pressure (DBP; millimeters of mercury). Noise data were provided by the Federal Office for the Environment. Stratified analyses by selfreported hypertension, cardiovascular disease (CVD), and diabetes were performed. Results: Mean noise exposure during the day and night was 51 dB(A) and 39 dB(A) for traffic noise, respectively, and 19 dB(A) and 17 dB(A) for railway noise. Adjusted regression models yielded significant effect estimates for a 10 dB(A) increase in railway noise during the night SBP β = 0.84; 95% confidence interval (CI): 0.22, 1.46; DBP β = 0.44; 95% CI: 0.06, 0.81 and day (SBP β = 0.60; 95% CI: 0.07, 1.13). Additional adjustment for nitrogen dioxide left effect estimates almost unchanged. Stronger associations were estimated for participants with chronic disease. Significant associations with traffic noise were seen only among participants with diabetes. Conclusion: We found evidence of an adverse effect of railway noise on blood pressure in this cohort population. Traffic noise was associated with higher blood pressure only in diabetics, possibly due to low exposure levels. The study results imply more severe health effects by transportation noise in vulnerable populations, such as adults with hypertension, diabetes, or CVD.
Organic electronics is emerging for large-area applications such as photovoltaic cells, rollable displays or electronic paper. Its future development and integration will require a simple, low-power ...organic memory, that can be written, erased and readout electrically. Here we demonstrate a non-volatile memory in which the ferroelectric polarisation state of an organic tunnel barrier encodes the stored information and sets the readout tunnel current. We use high-sensitivity piezoresponse force microscopy to show that films as thin as one or two layers of ferroelectric poly(vinylidene fluoride) remain switchable with low voltages. Submicron junctions based on these films display tunnel electroresistance reaching 1,000% at room temperature that is driven by ferroelectric switching and explained by electrostatic effects in a direct tunnelling regime. Our findings provide a path to develop low-cost, large-scale arrays of organic ferroelectric tunnel junctions on silicon or flexible substrates.
Accurate determination of stellar atmospheric parameters and elemental abundances is crucial for Galactic archaeology via large-scale spectroscopic surveys. In this paper, we estimate stellar ...atmospheric parameters -- effective temperature T sub( eff), surface gravity log g and metallicity Fe/H, absolute magnitudes M sub( V) and M sub( Ks), ...-element to metal (and iron) abundance ratio .../M (and .../Fe), as well as carbon and nitrogen abundances C/H and N/H from the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) spectra with a multivariate regression method based on kernel-based principal component analysis, using stars in common with other surveys (Hipparcos, Kepler, Apache Point Observatory Galactic Evolution Experiment) as training data sets. Both internal and external examinations indicate that given a spectral signal-to-noise ratio (SNR) better than 50, our method is capable of delivering stellar parameters with a precision of ~100 K for T sub( eff), ~0.1 dex for log g, 0.3-0.4 mag for M sub( V) and M sub( Ks), 0.1 dex for Fe/H, C/H and N/H, and better than 0.05 dex for .../M (.../Fe). The results are satisfactory even for a spectral SNR of 20. The work presents first determinations of C/H and N/H abundances from a vast data set of LAMOST, and, to our knowledge, the first reported implementation of absolute magnitude estimation directly based on a vast data set of observed spectra. The derived stellar parameters for millions of stars from the LAMOST surveys will be publicly available in the form of value-added catalogues. (ProQuest: ... denotes formulae/symbols omitted.)
Efficient manipulation of magnon spin transport is crucial for developing magnon-based spintronic devices. In this Letter, we provide proof of principle of a method for modulating the diffusive ...transport of thermal magnons in an yttrium iron garnet channel between injector and detector contacts. The magnon spin conductance of the channel is altered by increasing or decreasing the magnon chemical potential via spin Hall injection of magnons by a third modulator electrode. We obtain a modulation efficiency of 1.6%/mA at T=250 K. Finite element modeling shows that this could be increased to well above 10%/mA by reducing the thickness of the channel, providing interesting prospects for the development of thermal-magnon-based logic circuits.
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