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Electronic Health Record-Based Surveillance for Community Transmitted COVID-19 in the Emergency Department
Introduction: SARS-CoV-2, a novel coronavirus, manifests as a respiratory syndrome (COVID-19) and is the cause of an ongoing pandemic. The response to COVID-19 in the United States has been hampered by an overall lack of diagnostic testing capacity. To address uncertainty about ongoing levels of SARS-CoV-2 community transmission early in the pandemic, we aimed to develop a surveillance tool using readily available emergency department (ED) operations data extracted from the electronic health record (EHR). This involved optimizing the identification of acute respiratory infection (ARI)-related encounters and then comparing metrics for these encounters before and after the confirmation of SARS-CoV-2 community transmission.Methods: We performed an observational study using operational EHR data from two Midwest EDs with a combined annual census of over 80,000. Data were collected three weeks before and after the first confirmed case of local SARS-CoV-2 community transmission. To optimize capture of ARI cases, we compared various metrics including chief complaint, discharge diagnoses, and ARI-related orders. Operational metrics for ARI cases, including volume, pathogen identification, and illness severity, were compared between the pre- and post-community transmission timeframes using chi-square tests of independence.Results: Compared to our combined definition of ARI, chief complaint, discharge diagnoses, and isolation orders individually identified less than half of the cases. Respiratory pathogen testing was the top performing individual ARI definition but still only identified 72.2% of cases. From the pre to post periods, we observed significant increases in ED volumes due to ARI and ARI cases without identified pathogen.Conclusion: Certain methods for identifying ARI cases in the ED may be inadequate and multiple criteria should be used to optimize capture. In the absence of widely available SARS-CoV-2 testing, operational metrics for ARI-related encounters, especially the proportion of cases involving negative pathogen testing, are useful indicators for active surveillance of potential COVID-19 related ED visits
Partial anomalous pulmonary venous return mimics arterial positioning after central line placement for plasmapheresis
Case: A 61-year-old male who was status post right single lung transplant complicated by grade three primary graft dysfunction was admitted and mechanically ventilated for hypoxic respiratory failure. Donor specific antibody testing to human leukocyte antigens was positive. The protocol for antibody-mediated transplant rejection was initiated. One aspect of the protocol was a series of plasmapheresis procedures. In advance of the first plasmapheresis, central line placement was attempted via the left internal jugular vein. A chest x-ray showed a line that terminated to the left of the midline and raised concern for arterial placement (Figure 1). Blood gases from the line were: pH 7.72, pCO2 21 mmHg, pO2 369 mmHg, bicarbonate 28.4 mmol/L.Alex J. Griffith (Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital), Victoria Ray (MD, Department of Anesthesiology, University of Wisconsin Hospital), William N. Rose (MD, Department of Emergency Medicine, University of Wisconsin Hospital)Includes bibliographical reference
Dont Mess with Texas: Getting the Lone Star State to Net-Zero by 2050
The world is decarbonizing. Many countries, companies, and financial institutions have committed to cutting their emissions. Decarbonization commitments have been issued by: 136 countries including Canada, China, and the UK, at least 16 U.S. states including New York, Louisiana, and Virginia, and a third of the largest 2,000 publicly traded companies in the world, including Apple, Amazon, and Walmart, and numerous Texas companies like ExxonMobil, American and Southwest Airlines, Baker Hughes, and AT&T.1–9 These decarbonizing countries, states, cities, and companies are Texas's energy customers. If Texas ignores the challenge to decarbonize its economy, it may eventually face the more difficult challenge of selling carbon-intensive products to customers around the world who do not want them. We are already seeing this scenario beginning to play out with France canceling a liquified natural gas deal from Texas gas producers and both U.S. and international automakers announcing shifts to electric vehicles. Proactive net-zero emissions strategies might allow Texas to maintain energy leadership and grow the economy within a rapidly decarbonizing global marketplace.Thankfully, Texas is uniquely positioned to lead the world in the transition to a carbon-neutral energy economy. With the second highest Gross State Product in the US, the Texas economy is on par with countries like Canada, Italy, or Brazil. Thus, Texas's decisions have global implications. Texas also has an abundant resource of low-carbon energy sources to harness and a world-class workforce with technical capabilities to implement solutions at a large-scale quickly and safely. Texas has a promising opportunity to lead the world towards a better energy system in a way that provides significant economic benefits to the state by leveraging our renewable resources, energy industry expertise, and strong manufacturing and export markets for clean electricity, fuels, and products. The world is moving, with or without Texas, but it is likely to move faster--and Texas will be more prosperous--if Texans lead the way.There are many ways to fully decarbonize the Texas economy across all sectors by 2050. In this analysis, we present a Business as Usual (BAU) scenario and four possible pathways to Texas achieving state-wide net-zero emissions by 2050. Figure ES-1 provides a visual comparison of scenario conditions
Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice
The asymmetry of chemical nature at the hetero-structural interface offers an
unique opportunity to design desirable electronic structure by controlling
charge transfer and orbital hybridization across the interface. However, the
control of hetero-interface remains a daunting task. Here, we report the
modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n
superlattices by manipulating the periodic thickness with n unit cells of
SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy
rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K.
Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with
breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n
interface, and electronic charge transfer from Mn to Ti 3d orbitals across the
interface. Orbital hybridization accompanying the charge transfer results in
preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a
stronger electronic hopping integral along the out-of-plane direction and
corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that
interfacial orbital hybridization in superlattices of strongly correlated
oxides may be a promising approach to tailor electronic and magnetic properties
in device applications
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
Application of Equilibrium Models of Solution Hybridization to Microarray Design and Analysis
Background: The probe percent bound value, calculated using multi-state equilibrium models of solution hybridization, is shown to be useful in understanding the hybridization behavior of microarray probes having 50 nucleotides, with and without mismatches. These longer oligonucleotides are in widespread use on microarrays, but there are few controlled studies of their interactions with mismatched targets compared to 25-mer based platforms. Principal Findings: 50-mer oligonucleotides with centrally placed single, double and triple mismatches were spotted on an array. Over a range of target concentrations it was possible to discriminate binding to perfect matches and mismatches, and the type of mismatch could be predicted accurately in the concentration midrange (100 pM to 200 pM) using solution hybridization modeling methods. These results have implications for microarray design, optimization and analysis methods. Conclusions: Our results highlight the importance of incorporating biophysical factors in both the design and the analysis of microarrays. Use of the probe ‘‘percent bound’ ’ value predicted by equilibrium models of hybridization is confirmed to be important for predicting and interpreting the behavior of long oligonucleotide arrays, as has been shown for shor
FRAP Analysis on Red Alga Reveals the Fluorescence Recovery Is Ascribed to Intrinsic Photoprocesses of Phycobilisomes than Large-Scale Diffusion
BACKGROUND: Phycobilisomes (PBsomes) are the extrinsic antenna complexes upon the photosynthetic membranes in red algae and most cyanobacteria. The PBsomes in the cyanobacteria has been proposed to present high lateral mobility on the thylakoid membrane surface. In contrast, direct measurement of PBsome motility in red algae has been lacking so far. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we investigated the dynamics of PBsomes in the unicellular red alga Porphyridium cruentum in vivo and in vitro, using fluorescence recovery after photobleaching (FRAP). We found that part of the fluorescence recovery could be detected in both partially- and wholly-bleached wild-type and mutant F11 (UTEX 637) cells. Such partial fluorescence recovery was also observed in glutaraldehyde-treated and betaine-treated cells in which PBsome diffusion should be restricted by cross-linking effect, as well as in isolated PBsomes immobilized on the glass slide. CONCLUSIONS/SIGNIFICANCE: On the basis of our previous structural results showing the PBsome crowding on the native photosynthetic membrane as well as the present FRAP data, we concluded that the fluorescence recovery observed during FRAP experiment in red algae is mainly ascribed to the intrinsic photoprocesses of the bleached PBsomes in situ, rather than the rapid diffusion of PBsomes on thylakoid membranes in vivo. Furthermore, direct observations of the fluorescence dynamics of phycoerythrins using FRAP demonstrated the energetic decoupling of phycoerythrins in PBsomes against strong excitation light in vivo, which is proposed as a photoprotective mechanism in red algae attributed by the PBsomes in response to excess light energy
Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
Circulating glucose levels are tightly regulated. To identify novel glycemic loci, we performed meta-analyses of 21 genome-wide associations studies informative for fasting glucose (FG), fasting insulin (FI) and indices of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 non-diabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with FG/HOMA-B and two associated with FI/HOMA-IR. These include nine new FG loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and FAM148B) and one influencing FI/HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB/TMEM195 with type 2 diabetes (T2D). Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify T2D risk loci, as well as loci that elevate FG modestly, but do not cause overt diabetes
RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies
Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±
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