Development and Validation of eRADAR: A Tool Using EHR Data to Detect Unrecognized Dementia.

ObjectivesEarly recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR]).DesignRetrospective cohort study.SettingKaiser Permanente Washington (KPWA), an integrated healthcare delivery system.ParticipantsA total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples.MeasurementsEHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills).ResultsOverall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia.ConclusionThe eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019

Microglia-associated granule cell death in the normal adult dentate gyrus

Microglial cells are constantly monitoring the central nervous system for sick or dying cells and pathogens. Previous studies showed that the microglial cells in the dentate gyrus have a heterogeneous morphology with multipolar cells in the hilus and fusiform cells apposed to the granule cell layer both at the hilar and at the molecular layer borders. Although previous studies showed that the microglia in the dentate gyrus were not activated, the data in the present study show dying granule cells apposed by Iba1-immunolabeled microglial cell bodies and their processes both at hilar and at molecular layer borders of the granule cell layer. Initially, these Iba1-labeled microglial cells surround individual, intact granule cell bodies. When small openings in the plasma membrane of granule cells are observed, microglial cells are apposed to these openings. When larger openings in the plasma membrane occur at this site of apposition, the granule cells display watery perikaryal cytoplasm, watery nucleoplasm and damaged organelles. Such morphological features are characteristic of neuronal edema. The data also show that following this localized disintegration of the granule cell’s plasma membrane, the Iba1-labeled microglial cell body is found within the electron-lucent perikaryal cytoplasm of the granule cell, where it is adjacent to the granule cell’s nucleus which is deformed. We propose that granule cells are dying by a novel microglia-associated mechanism that involves lysis of their plasma membranes followed by neuronal edema and nuclear phagocytosis. Based on the morphological evidence, this type of cell death differs from either apoptosis or necrosis

Providing Grid Services With Heat Pumps: A Review

Abstract The integration of variable and intermittent renewable energy generation into the power system is a grand challenge to our efforts to achieve a sustainable future. Flexible demand is one solution to this challenge, where the demand can be controlled to follow energy supply, rather than the conventional way of controlling energy supply to follow demand. Recent research has shown that electric building climate control systems like heat pumps can provide this demand flexibility by effectively storing energy as heat in the thermal mass of the building. While some forms of heat pump demand flexibility have been implemented in the form of peak pricing and utility demand response programs, controlling heat pumps to provide ancillary services like frequency regulation, load following, and reserve have yet to be widely implemented. In this paper, we review the recent advances and remaining challenges in controlling heat pumps to provide these grid services. This analysis includes heat pump and building modeling, control methods both for isolated heat pumps and heat pumps in aggregate, and the potential implications that this concept has on the power system

Electric Field-Driven Water Dipoles: Nanoscale Architecture of Electroporation

<div><p>Electroporation is the formation of permeabilizing structures in the cell membrane under the influence of an externally imposed electric field. The resulting increased permeability of the membrane enables a wide range of biological applications, including the delivery of normally excluded substances into cells. While electroporation is used extensively in biology, biotechnology, and medicine, its molecular mechanism is not well understood. This lack of knowledge limits the ability to control and fine-tune the process. In this article we propose a novel molecular mechanism for the electroporation of a lipid bilayer based on energetics analysis. Using molecular dynamics simulations we demonstrate that pore formation is driven by the reorganization of the interfacial water molecules. Our energetics analysis and comparisons of simulations with and without the lipid bilayer show that the process of poration is driven by field-induced reorganization of water dipoles at the water-lipid or water-vacuum interfaces into more energetically favorable configurations, with their molecular dipoles oriented in the external field. Although the contributing role of water in electroporation has been noted previously, here we propose that interfacial water molecules are the main players in the process, its initiators and drivers. The role of the lipid layer, to a first-order approximation, is then reduced to a relatively passive barrier. This new view of electroporation simplifies the study of the problem, and opens up new opportunities in both theoretical modeling of the process and experimental research to better control or to use it in new, innovative ways.</p></div

Cultivation of Industrial Hemp on and Near Airports: Implications for Wildlife Use and Risk to Aviation Safety

Land-use planning on and near airports should consider possible revenue from land covers, associated maintenance costs, and potential for land covers to attract vertebrate species recognized as hazardous to aviation safety. The U.S. Federal Aviation Administration has expressed interest in recent attention given to industrial hemp (Cannabis sativa L.; hemp) as a revenue-producing land cover that might be cultivated on or near airports. Our purpose was to better understand the potential production value of hemp as well as its possible role in affecting aviation safety if cultivated on or near airports. Our objectives were to: (1) review the literature relative to a historical perspective of hemp cultivation in the United States, projected cultivation practices, and anticipated economic viability, (2) use our review to gather information on vertebrate use of hemp cultivars, and (3) revisit U.S. and international regulations on land covers near airports relative to attraction of species recognized as hazardous to aviation safety. We found, via review of peer-reviewed and gray literature, that hemp holds potential as an emerging crop in the United States, contributing to food, medicine, and biomass-derived products as well as evidence that birds will use, if not depredate, the crop. However, future markets promoting cultivation of hemp remain tentative. Further, there has been no objective quantification of bird and other wildlife use of hemp alone or as a component of a land cover matrix on or near airports and relative to implications for aviation safety. We make recommendations for future research on wildlife use of hemp and metrics necessary to inform aviation safety

Calcium Valence-to-Core X-ray Emission Spectroscopy: A Sensitive Probe of Oxo Protonation in Structural Models of the Oxygen-Evolving Complex

Calcium is an abundant, nontoxic metal that finds many roles in synthetic and biological systems including the oxygen-evolving complex (OEC) of photosystem II. Characterization methods for calcium centers, however, are underdeveloped compared to those available for transition metals. Valence-to-core X-ray emission spectroscopy (VtC XES) selectively probes the electronic structure of an element’s chemical environment, providing insight that complements the geometric information available from other techniques. Here, the utility of calcium VtC XES is established using an in-house dispersive spectrometer in combination with density functional theory. Spectral trends are rationalized within a molecular orbital framework, and Kβ_(2,5) transitions, derived from molecular orbitals with primarily ligand p character, are found to be a promising probe of the calcium coordination environment. In particular, it is shown that calcium VtC XES is sensitive to the electronic structure changes that accompany oxo protonation in Mn₃CaO₄-based molecular mimics of the OEC. Through correlation to calculations, the potential of calcium VtC XES to address unresolved questions regarding the mechanism of biological water oxidation is highlighted

Industrial Hemp as a Resource for Birds in Agroecosystems: Human–Wildlife Conflict or Conservation Opportunity?

Industrial hemp (Cannabis sativa L.; hemp) is an emerging crop in the United States with little known about bird use or the potential for birds to become an agricultural pest. We identified birds associated with hemp fields, using repeated visits to oilseed plots in North Dakota, USA (n = 6) and cannabinoid (CBD) plots in Florida, USA (n = 4) from August to November 2020. We did not control for plot area or density; our observations were descriptive only. We observed 10 species in hemp, 12 species flying over hemp, and 11 species both foraging in and flying over hemp fields in North Dakota. In Florida, we observed 4 species in hemp, 5 species flying over hemp, and 4 species exhibiting both behaviors. When we observed birds in hemp, we found them perched in the canopy or foraging on the ground. Counts were highest in oilseed and lowest in CBD varieties. The Florida sites were mainly CBD varieties, which explains lower species diversity and raw counts of birds given the lack of seeds produced. Maximum raw counts of the most common birds (mourning doves [Zenaida macroura] = 116; house finches [Haemorhous mexicanus] = 53; and American goldfinches [Spinus tristis] = 40) using very small fields (116–324 m2) in North Dakota suggest oilseed hemp could suffer yield losses but potentially benefit farmland bird conservation and act as a decoy crop to protect other commodities (e.g., sunflower [Helianthus annuus L.])

Rotational spectroscopic characterisation of the [D2,C,S] system: an update from the laboratory and theory

The synergy between high-resolution rotational spectroscopy and quantum-chemical calculations is essential for exploring future detection of molecules, especially when spectroscopy parameters are not available yet. By using highly correlated ab initio quartic force fields (QFFs) from explicitly correlated coupled cluster theory, a complete set of rotational constants and centrifugal distortion constants for D$_2$CS and cis/trans-DCSD isomers have been produced. Comparing our new ab initio results for D$_2$CS with new rotational spectroscopy laboratory data for the same species, the accuracy of the computed B and C rotational constants is within 0.1% while the A constant is only slightly higher. Additionally, quantum chemical vibrational frequencies are also provided, and these spectral reference data and new experimental rotational lines will provide additional references for potential observation of these deuterated sulfur species with either ground-based radio telescopes or space-based infrared observatories.Comment: 15 pages, 2 figures and 1 appendix table; published in Molecular Physics (Tim Lee Memorial Issue

Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation

Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism