What Can Hydrography Between the New England Slope, Bermuda and Africa Tell us About the Strength of the AMOC Over the Last 90 years?

The Gulf Stream is the only pathway in the subtropical North Atlantic by which warm water flows poleward. This transport of warm water and return of cold water at depth is called the Atlantic Meridional Overturning Circulation (AMOC). The dynamic method is applied to hydrocasts collected since the 1930s to estimate upper-ocean transport (0–1,000 m) between the U.S. Continental Slope and Bermuda and separately to Africa with focus on the longest directly observable timescale. Calculating transport between the Slope and Bermuda eliminates the Gulf Stream\u27s northern and southern recirculation gyres, while calculations between the Slope and Africa remove all other recirculating geostrophic flow. The net Slope-Bermuda upper-ocean transport is estimated to be 41.1 ± 0.4 Sv, decreasing by 2.0 ± 0.8 Sv between 1930 and 2020. The AMOC contribution is 18.4 ± 0.6 Sv, decreasing by 0.4 ± 0.6 Sv between 1930 and 2020

Recent Trends in Medicaid Spending and Use of Drugs with US Food and Drug Administration Accelerated Approval

State Medicaid programs have reported concerns about rising drug prices and spending, particularly regarding drugs entering the market through the accelerated approval program under the US Food and Drug Administration (FDA). The accelerated approval program enables the FDA to approve drugs on the basis of unverified surrogate end points, meaning that clinical benefits for these products are uncertain at the time of approval. However, state Medicaid programs are legally required to cover these drugs. Little is known about the set of products with accelerated approval over time, their use among Medicaid beneficiaries, or the magnitude of their financial influence on state Medicaid programs. OBJECTIVE To identify the number and class of drugs approved through the FDA’s accelerated approval pathway and analyze state Medicaid programs’ use and spending on these drugs from 2015 through 2019. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, biannual FDA reports were used to identify products granted accelerated approval and their associated indications approved between December 1992 and December 2020. State Medicaid Drug Utilization Data files available for 1992 through 2019 were used to estimate national totals for spending and use of outpatient drugs. MAIN OUTCOMES AND MEASURES National Medicaid use and gross and net spending on drugs with accelerated approval from 2015 through 2019. RESULTS Since the inception of the FDA’s accelerated approval pathway in 1992 through 2020, 216 product-indication pairs granted accelerated approval were identified, comprising 149 unique products. The composition of drugs approved through the pathway has changed over time, with 28 of 30 (93.3%) product-indication pairs receiving accelerated approval in 2020 being indicated for cancer. Relative to all outpatient prescription drugs paid for by Medicaid, products with accelerated approval ranged from 0.2% to 0.4% of use (1.3-2.4 million prescriptions annually). Despite their infrequent use, drugs with accelerated approval represented a minimum annual net spending on all drugs covered by Medicaid of 6.4% ($2.2 billion of$34.6 billion) in 2015 and a maximum of 9.1% ($2.5 billion of$27.6 billion) in 2018. Estimated annual gross spending on drugs with accelerated approval ranged from $4.2 billion to$4.9 billion over 2015 through 2019, and estimated net spending from $2.2 billion to$2.6 billion. CONCLUSIONS AND RELEVANCE In this cross-sectional study of 216 drugs granted accelerated approval, state spending on drugs approved through the FDA’s growing accelerated approval program represented an outsized amount of spending relative to use. Because drugs with accelerated approval have come to market on the basis of trials using surrogate end points, considerable amounts of this spending may have been attributable to products with unproven clinical benefits

New Pseudo-Phase Structure for α\alpha-Pu

In this paper we propose a new pseudo-phase crystal structure, based on an orthorhombic distortion of the diamond structure, for the ground-state $\alpha$-phase of plutonium. Electronic-structure calculations in the generalized-gradient approximation give approximately the same total energy for the two structures. Interestingly, our new pseudo-phase structure is the same as the Pu $\gamma$-phase structure except with very different b/a and c/a ratios. We show how the contraction relative to the $\gamma$ phase, principally in the $z$ direction, leads to an $\alpha$-like structure in the [0,1,1] plane. This is an important link between two complex structures of plutonium and opens new possibilities for exploring the very rich phase diagram of Pu through theoretical calculations

Toward a structural understanding of turbulent drag reduction: nonlinear coherent states in viscoelastic shear flows

Nontrivial steady flows have recently been found that capture the main structures of the turbulent buffer layer. We study the effects of polymer addition on these "exact coherent states" (ECS) in plane Couette flow. Despite the simplicity of the ECS flows, these effects closely mirror those observed experimentally: Structures shift to larger length scales, wall-normal fluctuations are suppressed while streamwise ones are enhanced, and drag is reduced. The mechanism underlying these effects is elucidated. These results suggest that the ECS are closely related to buffer layer turbulence.Comment: 5 pages, 3 figures, published version, Phys. Rev. Lett. 89, 208301 (2002

Intrinsic transverse momentum and the polarized Drell-Yan process

In this paper we study the cross section at leading order in $1/Q$ for polarized Drell-Yan scattering at measured lepton-pair transverse momentum $Q_T$. We find that for a hadron with spin $1/2$ the quark content at leading order is described by six distribution functions for each flavor, which depend on both the lightcone momentum fraction $x$, and the quark transverse momentum \bbox{k}_T^2. These functions are illustrated for a free-quark ensemble. The cross sections for both longitudinal and transverse polarizations are expressed in terms of convolution integrals over the distribution functions.Comment: 25 pages, REVTEX 3.0 (3 figures included in separate LATEX file using feynman.tex), NIKHEF-94-P1 (Revised version

Effects of acute lying and sleep deprivation on metabolic and inflammatory responses of lactating dairy cows

Dairy cows that are restricted from lying down have a reduced ability to sleep. In other species, sleep loss is a key risk factor for disease, mediated by changes in metabolic and inflammatory responses. The cumulative effect of lying and sleep deprivation on cow health is unknown. The objective was to determine the effects of lying and sleep deprivation on metabolic and inflammatory responses of dairy cows. Data were collected from 8 multiparous and 4 primiparous lactating cows (199 +/- 44 d in milk, 77 +/- 30 d pregnant; mean +/- standard deviation) enrolled in a study using a crossover design. Each cow was exposed to 2 treatments meant to induce sleep loss: (1) human disturbance (imposed by researchers making noise or physical contact when the cow's posture suggested sleep) and (2) lying deprivation (imposed by a wooden grid placed on the pen floor). Cows experienced a 24-h baseline period (d - 1) followed by a 24-h treatment period (d 0), with a 12-d washout period between treatments. Baseline and treatment periods were imposed from 2100 to 2059 h. Cows were housed in individual pens during the acclimation period (d - 3 and - 2), d - 1, and d 0. Nonesterified fatty acid and glucose concentrations were measured at 0300, 0900, 1500, and 2059 h on d - 1 and 0. Proinflammatory cytokine mRNA [tumor necrosis factor (TNF), interleukin-1B (IL1B), and interleukin-6 (IL6)] abundance in whole-blood leukocytes, both nonstimulated and stimulated with lipopolysaccharide, were assessed at 2059 h on d -1 (end of baseline) and d 0 (end of treatment). Nonesterified fatty acids and glucose varied by time of day but were not affected by treatment or day. The abundances of TNF and IL1B from both stimulated and nonstimulated cells were higher following 24 h of lying deprivation (d 0) compared with baseline (d -1). Abundance of IL6 was increased in nonstimulated cells after lying deprivation compared with baseline. In contrast, human disturbance for 24 h did not alter TNF, IL1B, or IL6 abundance relative to baseline levels. These results suggest that a short period of lying deprivation generally increases inflammatory responses but not metabolic responses.Peer reviewe

The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

To gain further knowledge on the preclinical phase of AD, we sought to characterize cognitive performance, volumetric MRI, amyloid PET, FDG PET, retinal amyloid, and plasma biomarkers in a cohort of non-demented adults with Down Syndrome (DS). The goal of the Down Syndrome Biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30-60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid PET 18F-florbetapir, 18F-fluorodeoxyglucose (18F-FDG) PET, and retinal amyloid imaging. In addition, plasma beta-amyloid species were measured and ApoE genotyping was performed. Consistent with previous autopsy studies, subjects demonstrated amyloid PET positivity reflecting fibrillar amyloid plaque deposition. Results from our multimodal analysis also suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Retinal amyloid imaging demonstrated presence of plaques. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971

Simulation of thermal conductivity and heat transport in solids

Using molecular dynamics (MD) with classical interaction potentials we present calculations of thermal conductivity and heat transport in crystals and glasses. Inducing shock waves and heat pulses into the systems we study the spreading of energy and temperature over the configurations. Phonon decay is investigated by exciting single modes in the structures and monitoring the time evolution of the amplitude using MD in a microcanonical ensemble. As examples, crystalline and amorphous modifications of Selenium and $\rm{SiO_2}$ are considered.Comment: Revtex, 8 pages, 11 postscript figures, accepted for publication in PR

Atomic structure and vibrational properties of icosahedral B4_4C boron carbide

The atomic structure of icosahedral B$_4$C boron carbide is determined by comparing existing infra-red absorption and Raman diffusion measurements with the predictions of accurate {\it ab initio} lattice-dynamical calculations performed for different structural models. This allows us to unambiguously determine the location of the carbon atom within the boron icosahedron, a task presently beyond X-ray and neutron diffraction ability. By examining the inter- and intra-icosahedral contributions to the stiffness we show that, contrary to recent conjectures, intra-icosahedral bonds are harder.Comment: 9 pages including 3 figures, accepted in Physical Review Letter

Synthesis of highly tetrahedral amorphous carbon by mixed-mode HiPIMS sputtering

Tetrahedral amorphous carbon films with an sp 3 content of 80% have been produced by high power impulse magnetron sputtering (HiPIMS) operating in a mixed sputtering/arc mode. In this mode, short-lived cathode spots form in the magnetic racetrack and produce large numbers of carbon ions. The spots move rapidly, inhibiting the formation of macroparticles. An argon pressure below 2.5 mTorr was critical for obtaining films with high sp 3 content, high stress, large Tauc gap and symmetrical Raman spectra, and all four quantities were strongly correlated