Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected Patients.

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus-infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and resultsWe identified 21 435 human immunodeficiency virus-infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus-related, and cardiovascular risk factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1), 1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When limited to antiretroviral-naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36-0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus-infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate

Low transverse emittance electron bunches from two-color laser-ionization injection

A method is proposed to generate low emittance electron bunches from two color laser pulses in a laser-plasma accelerator. A two-region gas structure is used, containing a short region of a high-Z gas (e.g., krypton) for ionization injection, followed by a longer region of a low-Z gas for post-acceleration. A long-laser-wavelength (e.g., 5 micron) pump pulse excites plasma wake without triggering the inner-shell electron ionization of the high-Z gas due to low electric fields. A short-laser-wavelength (e.g., 0.4 micron) injection pulse, located at a trapping phase of the wake, ionizes the inner-shell electrons of the high-Z gas, resulting in ionization-induced trapping. Compared with a single-pulse ionization injection, this scheme offers an order of magnitude smaller residual transverse momentum of the electron bunch, which is a result of the smaller vector potential amplitude of the injection pulse

Ghost Busting: PT-Symmetric Interpretation of the Lee Model

The Lee model was introduced in the 1950s as an elementary quantum field theory in which mass, wave function, and charge renormalization could be carried out exactly. In early studies of this model it was found that there is a critical value of g^2, the square of the renormalized coupling constant, above which g_0^2, the square of the unrenormalized coupling constant, is negative. Thus, for g^2 larger than this critical value, the Hamiltonian of the Lee model becomes non-Hermitian. It was also discovered that in this non-Hermitian regime a new state appears whose norm is negative. This state is called a ghost state. It has always been assumed that in this ghost regime the Lee model is an unacceptable quantum theory because unitarity appears to be violated. However, in this regime while the Hamiltonian is not Hermitian, it does possess PT symmetry. It has recently been discovered that a non-Hermitian Hamiltonian having PT symmetry may define a quantum theory that is unitary. The proof of unitarity requires the construction of a new time-independent operator called C. In terms of C one can define a new inner product with respect to which the norms of the states in the Hilbert space are positive. Furthermore, it has been shown that time evolution in such a theory is unitary. In this paper the C operator for the Lee model in the ghost regime is constructed exactly in the V/N-theta sector. It is then shown that the ghost state has a positive norm and that the Lee model is an acceptable unitary quantum field theory for all values of g^2.Comment: 20 pages, 9 figure

Electrical Characterization of 4H-SiC JFET Wafer: DC Parameter Variations for Extreme Temperature IC Design

This work reports DC electrical characterization of a 76 mm diameter 4H-SiC JFET test wafer fabricated as part of NASA's on-going efforts to realize medium-scale ICs with prolonged and stable circuit operation at temperatures as high as 500 degC. In particular, these measurements provide quantitative parameter ranges for use in JFET IC design and simulation. Larger than expected parameter variations were observed both as a function of position across the wafer as well as a function of ambient testing temperature from 23 degC to 500 degC

Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs

In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.https://www.liebertpub.com/doi/10.1089/biores.2020.0004Published versio

Evidence of Processing Non-Idealities in 4H-SiC Integrated Circuits Fabricated with Two Levels of Metal Interconnect

The fabrication and prolonged 500 C electrical testing of 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) with two levels of metal interconnect is reported in another submission to this conference proceedings. While some circuits functioned more than 1000 hours at 500 C, the majority of packaged ICs from this wafer electrically failed after less than 200 hours of operation in the same test conditions. This work examines the root physical degradation and failure mechanisms believed responsible for observed large discrepancies in 500 C operating time. Evidence is presented for four distinct issues that significantly impacted 500 C IC operational yield and lifetime for this wafer

Evidence of Processing Non-Idealities in 4H-SiC Integrated Circuits Fabricated With Two Levels of Metal Interconnect

The fabrication and prolonged 500 C electrical testing of 4H-SiC junction field effect transistor (JFET) integrated circuits (ICs) with two levels of metal interconnect is reported in another submission to this conference proceedings. While some circuits functioned more than 3000 hours at 500 C, the majority of packaged ICs from this wafer electrically failed after less than 200 hours of operation in the same test conditions. This work examines the root physical degradation and failure mechanisms believed responsible for observed large discrepancies in 500 C operating time. Evidence is presented for four distinct issues that significantly impacted 500 C IC operational yield and lifetime for this wafer

From AKNS to derivative NLS hierarchies via deformations of associative products

Using deformations of associative products, derivative nonlinear Schrodinger (DNLS) hierarchies are recovered as AKNS-type hierarchies. Since the latter can also be formulated as Gelfand-Dickey-type Lax hierarchies, a recently developed method to obtain 'functional representations' can be applied. We actually consider hierarchies with dependent variables in any (possibly noncommutative) associative algebra, e.g., an algebra of matrices of functions. This also covers the case of hierarchies of coupled DNLS equations.Comment: 22 pages, 2nd version: title changed and material organized in a different way, 3rd version: introduction and first part of section 2 rewritten, taking account of previously overlooked references. To appear in J. Physics A: Math. Ge