1,198 research outputs found

    The Potential Trajectory of Carbapenem-Resistant Enterobacteriaceae, an Emerging Threat to Health-Care Facilities, and the Impact of the Centers for Disease Control and Prevention Toolkit.

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    Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half

    Steinberg modules and Donkin pairs

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    We prove that in positive characteristic a module with good filtration for a group of type E6 restricts to a module with good filtration for a subgroup of type F4. (Recall that a filtration of a module for a semisimple algebraic group is called good if its layers are dual Weyl modules.) Our result confirms a conjecture of Brundan for one more case. The method relies on the canonical Frobenius splittings of Mathieu. Next we settle the remaining cases, in characteristic not 2, with a computer-aided variation on the old method of Donkin.Comment: 16 pages; proof of Brundan's conjecture adde

    Dynamic microRNA activity identifies therapeutic targets in trastuzumab‐resistant HER2+ breast cancer

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    MicroRNAs (miRNAs) are implicated in numerous physiologic and pathologic processes, such as the development of resistance to chemotherapy. Determining the role of miRNAs in these processes is often accomplished through measuring miRNA abundance by polymerase chain reaction, sequencing, or microarrays. We have developed a system for the large‐scale monitoring of dynamic miRNA activity and have applied this system to identify the contribution miRNA activity to the development of trastuzumab resistance in a cell model of HER2+ breast cancer. MiRNA activity measurements identified significantly different activity levels between BT474 cells (HER2+ breast cancer) and BT474R cells (HER2+ breast cancer cells selected for resistance to trastuzumab). We created a library of 32 miRNA reporter constructs, which were delivered by lentiviral transduction into cells, and miRNA activity was quantified by bioluminescence imaging. Upon treatment with the bioimmune therapy, trastuzumab, the activity of 11 miRNAs were significantly altered in parental BT474 cells, and 20 miRNAs had significantly altered activity in the therapy‐resistant BT474R cell line. A combination of statistical, network and classification analysis was applied to the dynamic data, which identified miR‐21 as a controlling factor in trastuzumab response. Our data suggested downregulation of miR‐21 activity was associated with resistance, which was confirmed in an additional HER2+ breast cancer cell line, SKBR3. Collectively, the dynamic miRNA activity measurements and analysis provided a system to identify new potential therapeutic targets in treatment‐resistant cancers.MicroRNAs (miRNAs) are often dysrgulated in cancer and can give rise to drug resistance. Identifying the mechanisms for resistance may lead to new This work used an array of miRNA activity reporters to identify miR‐21 as a mediator of trastuzumab resistance in breast cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/1/bit26791.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/2/bit26791_am.pd

    Towards Deconstruction of the Type D (2,0) Theory

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    We propose a four-dimensional supersymmetric theory that deconstructs, in a particular limit, the six-dimensional (2,0)(2,0) theory of type DkD_k. This 4d theory is defined by a necklace quiver with alternating gauge nodes O(2k)\mathrm{O}(2k) and Sp(k)\mathrm{Sp}(k). We test this proposal by comparing the 6d half-BPS index to the Higgs branch Hilbert series of the 4d theory. In the process, we overcome several technical difficulties, such as Hilbert series calculations for non-complete intersections, and the choice of O\mathrm{O} versus SO\mathrm{SO} gauge groups. Consistently, the result matches the Coulomb branch formula for the mirror theory upon reduction to 3d

    Gravitational mechanisms to self-tune the cosmological constant: obstructions and ways forward

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    Gravitational models of self-tuning are those in which vacuum energy has no observable effect on spacetime curvature, even though it is a priori unsuppressed below the cut-off. We complement Weinberg's no go theorem by studying field theoretic completions of self-adjustment allowing for broken translations as well as other generalisations, and identify new obstructions. Our analysis uses a very general Källén-Lehmann spectral representation of the exchange amplitude for conserved sources of energy-momentum and exploits unitarity and Lorentz invariance to show that a transition from self-tuning of long wavelength sources to near General Relativity on shorter scales is generically not possible. We search for novel ways around our obstructions and highlight two interesting possibilities. The first is an example of a unitary field configuration on anti-de Sitter space with the desired transition from self-tuning to GR. A second example is motivated by vacuumenergy sequestering

    Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus

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    Aims Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose-responsive gene in pancreatic B-cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21-1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM. Methods The frequency distribution of a 3' UTR single nucleotide polymorphism (SNP) in TXNIP was investigated in subjects with normal glucose tolerance (NGT; n = 379), impaired glucose tolerance (IGT; n = 228) and Type 2 DM (n = 230). Metabolic data were used to determine the effect of this SNP on parameters associated with lipid and glucose metabolism. Results The frequency of the TXNIP variation did not differ between groups, but within the group of diabetic subjects, carriers of the TXNIP-T variant had 1.6-fold higher triglyceride concentrations (P = 0.015; n = 136) and a 5.5-mmHg higher diastolic blood pressure (P = 0.02; n = 212) than homozygous carriers of the common C-allele, whereas in non-diabetic subjects fasting glucose was 0.26 mmol/l lower (P = 0.002; n = 478) in carriers of the T-allele. Moreover, a significant interaction between plasma glucose concentrations and TXNIP polymorphism on plasma triglycerides was observed (P = 0.012; n = 544). Conclusion This is the first report to implicate TXNIP in a human disorder of energy metabolism, Type 2 diabetes. The effect of TXNIP on triglycerides is influenced by plasma glucose concentrations, suggesting that the biological relevance of TXNIP variations may be particularly relevant in recurrent episodes of hyperglycaemia

    A 5d/3d duality from relativistic integrable system

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    We propose and prove a new exact duality between the F-terms of supersymmetric gauge theories in five and three dimensions with adjoint matter fields. The theories are compactified on a circle and are subject to the Omega deformation. In the limit proposed by Nekrasov and Shatashvili, the supersymmetric vacua become isolated and are identified with the eigenstates of a quantum integrable system. The effective twisted superpotentials are the Yang-Yang functional of the relativistic elliptic Calogero-Moser model. We show that they match on-shell by deriving the Bethe ansatz equation from the saddle point of the five-dimensional partition function. We also show that the Chern-Simons terms match and extend our proposal to the elliptic quiver generalizations.Comment: 30 pages, 4 figures. v2: typo corrected, references adde

    Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

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    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans
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