Influence of diabetes complications on HbA(1c) treatment goals among older US adults: A cost-effectiveness analysis

OBJECTIVE Guidelines on the standard care of diabetes recommend that glycemic treatment goals for older adults consider the patient’s complications and life expectancy. In this study, we examined the influence of diabetes complications and associated life expectancies on the cost-effectiveness (CE) of HbA1c treatment goals. RESEARCH DESIGN AND METHODS We used data from the 2011–2016 National Health and Nutrition Examination Survey (NHANES) to generate nationally representative subgroups of older individuals with diabetes with various health states. We used the Centers for Disease Control and Prevention–RTI International diabetes CE model to estimate the long-term consequences of two treatment goals—a stringent control goal (HbA1c $82,413 per QALY). Further, a stringent goal was not cost-effective when an individual had less than 7 years of life remaining. CONCLUSIONS Our findings support the guideline recommendation that glycemic goals for older adults should consider the complexity of their complications and their life expectancy from a CE perspective

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

A new concept for the combination of optical interferometers and high-resolution spectrographs

The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Dorsal root ganglia control nociceptive input to the central nervous system

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support “gating” of pain information by DRGs and suggest new therapeutic approaches for pain relief

Performance analysis of wind fence models when used for truck protection under crosswind through numerical modeling

This paper is focused on truck aerodynamic analysis under crosswind conditions by means of numerical modeling. The truck was located on the crest of an embankment during the study. In order to analyze the performance of three wind fence models, the truck's aerodynamic coefficients were obtained and compared in two different situations either with or without the wind fences installed. In addition, the effect of both height and porosity of wind fence models on the aerodynamic coefficients acting on truck with respect to separation distance between the truck and the wind fence, was analyzed. A finite volume (or computational fluid dynamic) code was used to carry out the numerical modeling. The Reynolds-averaged Navier?Stokes (RANS) equations along with the k?? SST turbulence model were used to predict the behavior of turbulent flow. With respect to the results, the influence of the distance on the rollover coefficient is soft for all height values studied except for the lowest value (1 m of fence height), where the maximum value of rollover coefficient was obtained for the truck position closer to the fence. Regarding fence porosity, its effect on rollover coefficient is stronger for truck positions on road closer to the wind fence model.This work was supported by the OASIS Research Project that was co-financed by CDTI (Spanish Science and Innovation Ministry) and developed with the Spanish companies: Iridium, OHL Concesiones, Abertis, Sice, Indra, Dragados, OHL, Geocisa, GMV, Asfaltos Augusta, Hidrofersa, Eipsa, PyG, CPS, AEC and Torre de Comares Arquitectos S.L. and 16 research centres. The authors would also like to thank the GICONSIME research group of the University of Oviedo (Spain) for their collaboration in this research

Performance and bacterial community shifts during phosphogypsum biotransformation

Phosphogypsum (PG) is an industrial waste composed mainly by sulfate, turning it a suitable sulfate source for sulfate-reducing bacteria (SRB). In the present work, the capability of two SRB communities, one enriched from Portuguese PG (culture PG) and the other from sludge from a wastewater treatment plant (culture WWT-1), to use sulfate from PG was compared. In addition, the impact of this sulfate-rich waste in the microbial community was assessed. The highest efficiency in terms of sulfate reduction was observed with culture WWT-1. The bacterial composition of this culture was not significantly affected when sodium sulfate from the nutrient medium was replaced by PG as a sulfate source. Next generation sequencing (NGS) showed that this community was phylogenetically diverse, composed by bacteria affiliated to Clostridium, Arcobacter, and Sulfurospirillum genera and by SRB belonging to Desulfovibrio, Desulfomicrobium, and Desulfobulbus genera. In contrast, the bacterial structure of the community enriched from PG was modified when sodium sulfate was replaced by PG as the sulfate source. This culture, which showed the poorest performance in the use of sulfate from PG, was mainly composed by SRB related to Desulfosporosinus genus. The present work provides new information regarding the phylogenetic characterization of anaerobic bacterial communities with the ability to use PG as sulfate donor, thus, contributing to improve the knowledge of microorganisms suitable to be used in PG bioremediation. Additionally, this paper demonstrates that an alternative to lactate and low-cost carbon source (wine wastes) can be used efficiently for that purpose

Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36