Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study ...thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly associated with AD pathology and cognitive impairment. This module was enriched in AD genetic risk factors and in microglia and astrocyte protein markers associated with an anti-inflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were elevated in cerebrospinal fluid in early stages of the disease. In this study of >2,000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brains that may serve as therapeutic targets and fluid biomarkers for the disease.
Membrane-less organelles are cellular structures which arise through the phenomenon of phase separation. This process enables compartmentalization of specific sets of macromolecules (e.g., proteins, ...nucleic acids), thereby regulating cellular processes by increasing local concentration, and modulating the structure and dynamics of their constituents. Understanding the connection between structure, material properties and function of membrane-less organelles requires inter-disciplinary approaches, which address length and timescales that span several orders of magnitude (e.g., Ångstroms to micrometer, picoseconds to hours). In this review, we discuss the wide variety of methods that have been applied to characterize the morphology, rheology, structure and dynamics of membrane-less organelles and their components, in vitro and in live cells.
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•Membrane-less organelles arise through the phenomenon of phase separation.•Select proteins and nucleic acids are concentrated within phase-separated bodies.•Structure and dynamics of the molecular networks affect organelle properties and function.•Structure and dynamic features span broad length and timescales.•Integrative methods are needed in studies of membrane-less organelles.
Maintaining soil organic carbon (SOC) in frequently tilled, intensive organic vegetable production systems is a challenge that is not well understood. Compost and cover crops are often used to add ...organic matter to the soil in these systems. Compost contributes relatively stabilized carbon (C) while cover crops provide readily degradable (labile) organic matter. Our objectives were to quantify C inputs, and to assess the effects of urban yard-waste compost, winter cover crop frequency and cover crop type on SOC and labile C stocks during eight years of intensive, organic production that usually included two vegetable crops per year in a long-term systems study in Salinas, California. Total C inputs from pelleted fertilizer, compost, vegetable transplant potting mix, vegetable residue and cover crops, including estimates of below ground inputs, ranged from 40 to 108 Mg ha-1 in the five systems evaluated. Following a rapid decline in SOC stocks in year 1, compost had the largest effect on SOC stocks increasing mean SOC over years 2 to 8 by an average of 9.4 Mg ha-1, while increased cover crop frequency (annual vs. quadrennial) led to an additional 3.4 Mg ha-1 increase. In contrast, cover cropping frequency had the largest effect on permanganate oxidizable labile C (POX-C), increasing POX-C by 26% after 8 years. Labile POX-C was well correlated with microbial biomass C and nitrogen. Compost had the greatest effect on total SOC stocks, while increasing cover crop frequency altered the composition of SOC by increasing the proportion of labile C. These results suggest that frequent winter cover cropping has a greater potential than compost to increase nutrient availability and vegetable yields in high-input, tillage intensive vegetable systems.
A revisionist account of technology's role in the aesthetics, spaces and politics of transatlantic avant-gardesExplores of a range of key avant-garde formations in the modernist transatlantic period, ...from the Italian futurists and English Vorticists to the Dada-surrealist and post-Harlem Renaissance African American experimentalistsExplores writers' and artists' inventions as well as their texts, and involves them directly in the messy transductions of technology in cultureDraws on previously unknown photos, manuscripts and other evidence that reveals the untold story of Bob and Rose Brown's 'reading machine' - a cross-disciplinary, meta-formational, and transnational project that proposed to transform the everyday act of readingReading Machines in the Modernist Transatlantic provides a new account of aesthetic and technological innovation, from the Machine Age to the Information Age. Drawing on a wealth of archival discoveries, it argues that modernist avant-gardes used technology not only as a means of analysing culture, but as a way of feeding back into it. As well as uncovering a new invention by Mina Loy, the untold story of Bob Brown's 'reading machine' and the radical technicities of African American experimentalists including Gwendolyn Bennett and Ralph Ellison, the book places avant-gardes at the centre of innovation across a variety of fields. From dazzle camouflage to microfilm, and from rail networks to broadcast systems, White explores how vanguardists harnessed socio-technics to provoke social change.
Systems differed by annual compost additions (0 vs. 7.6 Mg ha-1 before each vegetable crop), cover crop type (legume-rye, mustard or cereal rye alone) and cover cropping frequency (quadrennially vs. ...annually planted). https://doi.org/10.1371/journal.pone.0307250.g005 thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Fig 10. Carbon inputs, soil organic carbon and permanganate oxidizable carbon ANOVA F-statistics and significance. https://doi.org/10.1371/journal.pone.0307250.t001 Supporting information S3 Fig. Soil organic carbon stocks over 8 years in three organic vegetable systems in Salinas, CA that all received annual compost additions (7.6 Mg ha-1 before each vegetable crop) and differed by annually planted cover crop type. https://doi.org/10.1371/journal.pone.0307250.s001 (TIF) S1 Table.
Objective
To estimate dementia's incremental cost to the traditional Medicare program.
Data Sources
Health and Retirement Study (HRS) survey‐linked Medicare part A and B claims from 1991 to 2012.
...Study Design
We compared Medicare expenditures for 60 months following a claims‐based dementia diagnosis to those for a randomly selected, matched comparison group.
Data Collection/Extraction Methods
We used a cost estimator that accounts for differential survival between individuals with and without dementia and decomposes incremental costs into survival and cost intensity components.
Principal Findings
Dementia's five‐year incremental cost to the traditional Medicare program is approximately $15 700 per patient, nearly half of which is incurred in the first year after diagnosis. Shorter survival with dementia mitigates the incremental cost by about $2650. Increased costs for individuals with dementia were driven by more intensive use of Medicare part A covered services. The incremental cost of dementia was about $7850 higher for females than for males because of sex‐specific differential mortality associated with dementia.
Conclusions
Dementia's cost to the traditional Medicare program is significant. Interventions that target early identification of dementia and preventable inpatient and post‐acute care services could produce substantial savings.
Efficient use of nitrogen (N) is essential to protect water quality in high-input organic vegetable production systems, but little is known about the long-term effects of organic management on N mass ...balances. We measured soil N and tabulated N inputs (organic fertilizers, compost, irrigation water, atmospheric deposition, cover crop seed, vegetable transplant plugs and fixation by legume cover crops) and exports in harvested crops (lettuce, broccoli) over eight years to calculate soil surface and soil system N mass balances for the Salinas Organic Cropping Systems study in Salinas, CA. Our objectives were to 1) quantify the long-term effects of compost, cover crop frequency and cover crop type on soil N, cover crop and vegetable crop N uptake, and yield, and 2) tabulate N balances to assess the effects of these factors on N export in harvested crops, soil N storage and potential N loss. Results show that across all systems only 13 to 23% of N inputs were exported in harvest. Annual compost applications increased soil N stocks but had little effect on vegetable N uptake or yield, increasing the cumulative soil system N balance surplus over eight years by 999 kg ha-1, relative to the system receiving organic fertilizers alone. Annually planted winter cover crops increased N availability, crop uptake and export; however, biological N fixation by legumes negated the positive effect of increased harvest exports on the balance surplus in the legume-rye cover cropped system. Over eight years, rye cover crops improved system performance and reduced the cumulative N surplus by 384 kg ha-1 relative to the legume-rye mixture by increasing N retention and availability without increasing N inputs. Reduced reliance on external compost inputs and increased use of annually planted non-legume cover crops can improve efficient N use and cropping system yield, consequently improving environmental performance.
OBJECTIVE:The objective of this study was to determine differences in health care utilization, process of diabetes care, care satisfaction, and health status for Medicare Advantage (MA) and ...traditional Medicare (TM) beneficiaries with and without diabetes.
METHODS:Using the 2010–2016 Medicare Current Beneficiary Survey, we identified MA and TM beneficiaries with and without diabetes. To address the endogenous plan choice between MA and TM, we used an instrumental variable approach. Using marginal effects, we estimated differences in the outcomes between MA and TM beneficiaries with and without diabetes.
RESULTS:Our instrumental variable analysis showed that compared with TM beneficiaries with diabetes, MA beneficiaries with diabetes had less annual health care utilization, including −22.4 medical provider visits 95% confidence interval (CI)−23.6 to −21.1 and −3.4 outpatient hospital visits (95% CI−3.8 to −3.0). A significant difference between MA and TM beneficiaries without diabetes was only observed in medical provider visits and the difference was greater among beneficiaries with diabetes than beneficiaries without diabetes (−12.5 medical provider visits; 95% CI−15.9 to −9.2). While we did not detect significant differences in 5 measures of the process of diabetes care between MA and TM beneficiaries with diabetes, there were inconsistent results in the other 3 measures. There were no or marginal differences in care satisfaction and health status between MA and TM beneficiaries with and without diabetes.
CONCLUSIONS:MA enrollment was associated with lower health care utilization without compromising care satisfaction and health status, particularly for beneficiaries with diabetes. MA may have a more efficient care delivery system for beneficiaries with diabetes.
Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to ...improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age-specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community-based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.
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