Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl

Background: A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2–related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention.<p></p> Methods and Results: We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min−1 1.73 m−2) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl– and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events.<p></p> Conclusions: Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events.<p></p&gt

Results of a 2-year randomized, controlled obesity prevention trial: Effects on diet, activity and sleep behaviors in an at-risk young adult population

Excess weight gain tends to occur in young adulthood. However, research examining effective weight-related interventions for this age group has been limited. As one of seven trials in the EARLY Trials consortium (Early Adult Reduction of weight through LifestYle intervention), the CHOICES Study (Choosing Healthy Options in College Environments and Settings) tested effects of a technology-integrated, young adult weight gain prevention intervention. It was a randomized controlled trial with assessments at baseline (2011) and 4-, 12- and 24-months post-intervention initiation and included 441 participants (ages 18-35) who were students at three Minnesota community colleges. The 24-month intervention included a 1-credit academic course and social networking and support online intervention. This analysis examined effects on 12 secondary behavioral outcomes across three domains: diet (fast food, sugary beverages, breakfast, at-home meal preparation), physical activity/screen time (minutes and energy expenditure in leisure time physical activity, television viewing, leisure time computer use) and sleep (hours of sleep, time required to fall asleep, days not getting enough rest, difficulty staying awake). The intervention resulted in significant reductions in fast food (p=0.007) but increases in difficulty staying awake (p=0.015). There was limited evidence of other behavior changes at 4 months (0.05<p<0.1) in the expected direction but differences by treatment condition dissipated over time. Analyses examining summary treatment effects (i.e., modeling effects on all behavioral outcomes simultaneously) indicated significant overall effects (p=0.014), largely driven by 4-month results (p=0.005). Additional research is needed to understand effective obesity prevention among young adults, particularly when addressing multiple weight-related outcomes

The Inflaton and Time in the Matter-Gravity System

The emergence of time in the matter-gravity system is addressed within the context of the inflationary paradigm. A quantum minisuperspace-homogeneous minimally coupled inflaton system is studied with suitable initial conditions leading to inflation and the system is approximately solved in the limit for large scale factor. Subsequently normal matter (either non homogeneous inflaton modes or lighter matter) is introduced as a perturbation and it is seen that its presence requires the coarse averaging of a gravitational wave function (which oscillates at trans-Planckian frequencies) having suitable initial conditions. Such a wave function, which is common for all types of normal matter, is associated with a ``time density'' in the sense that its modulus is related to the amount of time spent in a given interval (or the rate of flow of time). One is then finally led to an effective evolution equation (Schroedinger Schwinger-Tomonaga) for ``normal'' matter. An analogy with the emergence of a temperature in statistical mechanics is also pointed out.Comment: 14 pages, late

A screen-printing method for manufacturing of current collectors for structural batteries

Structural carbon fibre composite batteries are a type of multifunctional batteries that combine the energy storage capability of a battery with the load-carrying ability of a structural material. To extract the current from the structural battery cell, current collectors are needed. However, current collectors are expensive, hard to connect to the electrode material and add mass to the system. Further, attaching the current collector to the carbon fibre electrode must not affect the electrochemical properties negatively or requires time-consuming, manual steps. This paper presents a proof-of-concept method for screen-printing of current collectors for structural carbon fibre composite batteries using silver conductive paste. Current collectors are screen-printed directly on spread carbon fibre tows and a polycarbonate carrier film. Experimental results show that the electrochemical performance of carbon fibre vs lithium metal half-cells with the screen-printed collectors is similar to reference half-cells using metal foil and silver adhered metal-foil collectors. The screen-printed current collectors fulfil the requirements for electrical conductivity, adhesion to the fibres and flexible handling of the fibre electrode. The screen-printing process is highly automatable and allows for cost-efficient upscaling to large scale manufacturing of arbitrary and complex current collector shapes. Hence, the screen-printing process shows a promising route to realization of high performing current collectors in structural batteries and potentially in other types of energy storage solutions

A Supersymmetric SO(10) Model with Inflation and Cosmic Strings

We have built a supersymmetric SO(10) model consistent with cosmological observations. The model gives rise to a false vacuum hybrid inflationary scenario which solves the monopole problem. We argue that this type of inflationary scenario is generic in supersymmetric SO(10) model, and arises naturally from the theory. Neither any external field nor any external symmetry has to be added. It can just be a consequence of the theory. In our specific model, at the end of inflation, cosmic strings form. The properties of the strings are presented. The cosmic background radiation anisotropies induced by the inflationary perturbations and the cosmic strings are estimated. The model produces a stable lightest superparticle and a very light left-handed neutrino which may serve as the cold and hot dark matter. The properties of a mixed cosmic string-inflationary large scale structure formation scenario are discussed.Comment: 32 pages, uses RevTex. Misprint in a referenc

Natural Double Inflation in Supergravity

We propose a natural double inflation model in supergravity. In this model, chaotic inflation first takes place by virtue of the Nambu-Goldstone-like shift symmetry, which guarantees the absence of the exponential factor in the potential for the inflaton field. During chaotic inflation, an initial value of the second inflation (new inflation) is set. In this model, the initial value of new inflation can be adequately far from the local maximum of the potential for new inflation due to the small linear term of the inflaton in the K\"ahler potential. Therefore, the primordial fluctuations within the present horizon scale may be attributed to both inflations; that is, the first chaotic inflation produces the primordial fluctuations on the large cosmological scales while the second new inflation on the smaller scales. The successive decay of the inflaton for new inflation leads to a reheating temperature low enough to avoid the overproduction of gravitinos in a wide range of the gravitino mass.Comment: 13 pages, to appear in Phys. Rev.

Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis.

Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI

Double Inflation in Supergravity and the Large Scale Structure

The cosmological implication of a double inflation model with hybrid + new inflations in supergravity is studied. The hybrid inflation drives an inflaton for new inflation close to the origin through supergravity effects and new inflation naturally occurs. If the total e-fold number of new inflation is smaller than $\sim 60$, both inflations produce cosmologically relevant density fluctuations. Both cluster abundances and galaxy distributions provide strong constraints on the parameters in the double inflation model assuming $\Omega_0=1$ standard cold dark matter scenario. The future satellite experiments to measure the angular power spectrum of the cosmic microwave background will make a precise determination of the model parameters possible.Comment: 19 pages (RevTeX file

Weight-Gain Reduction Among 2-Year College Students: The CHOICES RCT

The young adult years have been recognized as an influential period for excess weight gain. Non-traditional students and those attending 2-year community colleges are at particularly high risk for a range of adverse weight-related outcomes

Evading the cosmological domain wall problem

Discrete symmetries are commonplace in field theoretical models but pose a severe problem for cosmology since they lead to the formation of domain walls during spontaneous symmetry breaking in the early universe. However if one of the vacuua is favoured over the others, either energetically, or because of initial conditions, it will eventually come to dominate the universe. Using numerical methods, we study the evolution of the domain wall network for a variety of field configurations in two and three dimensions and quantify the rate at which the walls disappear. Good agreement is found with a recent analytic estimate of the termination of the scaling regime of the wall network.Comment: 17 pages (revtex), including 9 figures (epsf); Revised to include test of numerical approximation used; No change in results or conclusions; accepted for publication in Phys Rev D. PostScript available at ftp://ftp.physics.ox.ac.uk/pub/local/users/sarkar/Domainwalls.ps.g