Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis

Background: 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. / Methods: Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0–3) of cardiac uptake. / Results: Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. / Conclusion: Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management

The ABC7 regimen: a new approach to metastatic breast cancer using seven common drugs to inhibit epithelial-to-mesenchymal transition and augment capecitabine efficacy.

Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities. Chemotherapy, radiation, and surgery provoke EMT in cancer generally and in breast cancer specifically. ABC7 uses standard doses of capecitabine as used in treating breast cancer today. In addition, ABC7 uses 1) an older psychiatric drug, quetiapine, to block RANK signaling; 2) pirfenidone, an anti-fibrosis drug to block TGF-beta signaling; 3) rifabutin, an antibiotic to block beta-catenin signaling; 4) metformin, a first-line antidiabetic drug to stimulate AMPK and inhibit mammalian target of rapamycin, (mTOR); 5) propranolol, a beta-blocker to block beta-adrenergic signaling; 6) agomelatine, a melatonergic antidepressant to stimulate M1 and M2 melatonergic receptors; and 7) ribavirin, an antiviral drug to prevent eIF4E phosphorylation. All these block the signaling pathways ? RANK, TGF-beta, mTOR, beta-adrenergic receptors, and phosphorylated eIF4E ? that have been shown to trigger EMT and enhance breast cancer growth and so are worthwhile targets to inhibit. Agonism at MT1 and MT2 melatonergic receptors has been shown to inhibit both breast cancer EMT and growth. This ensemble was designed to be safe and augment capecitabine efficacy. Given the expected outcome of metastatic breast cancer as it stands today, ABC7 warrants a cautious trial

Challenges to support edge-as-a-service

A new era in telecommunications is emerging. Virtualized networking functions and resources will offer network operators a way to shift the balance of expenditure from capital to operational, opening up networks to new and innovative services. This article introduces the concept of edge as a service (EaaS), a means of harnessing the flexibility of virtualized network functions and resources to enable network operators to break the tightly coupled relationship they have with their infrastructure and enable more effective ways of generating revenue. To achieve this vision, we envisage a virtualized service access interface that can be used to programmatically alter access network functions and resources available to service providers in an elastic fashion. EaaS has many technically and economically difficult challenges that must be addressed before it can become a reality; the main challenges are summarized in this article

Coherent pairing states for the Hubbard model

We consider the Hubbard model and its extensions on bipartite lattices. We define a dynamical group based on the $\eta$-pairing operators introduced by C.N.Yang, and define coherent pairing states, which are combinations of eigenfunctions of $\eta$-operators. These states permit exact calculations of numerous physical properties of the system, including energy, various fluctuations and correlation functions, including pairing ODLRO to all orders. This approach is complementary to BCS, in that these are superconducting coherent states associated with the exact model, although they are not eigenstates of the Hamiltonian.Comment: 5 pages, RevTe

Systematics of the Quadrupole-Quadrupole Interaction and Convergence Properties

Our main concern in this work is to show how higher shell admixtures affect the spectrum of a Q.Q interaction. We first review how, in the valence space, the familiar SU(3) result for the energy spectrum can be obtained using a coordinate space Q.Q interaction rather than the Elliott one which is symmetric in r and p. We then reemphasize that the Elliott spectrum goes as L(L+1) where L is the orbital angular momentum. While in many cases this is compatible with the rotational formula which involves I(I+1), where I is the total angular momentum, there are cases, e.g. odd-odd nuclei, where there is disagreement. Finally, we consider higher shell admixtures and devise a scheme so as to obtain results, with the Q.Q interaction, which converge as the model spaces are increased. We consider not only ground state rotational bands but also those that involve intruder states.Comment: 13 pages, Revtex, to appear in Annals of Physic

Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIα-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry

Small oscillations of a chiral Gross-Neveu system

We study the small oscillations regime (RPA approximation) of the time-dependent mean-field equations, obtained in a previous work, which describe the time evolution of one-body dynamical variables of a uniform Chiral Gross-Neveu system. In this approximation we obtain an analytical solution for the time evolution of the one-body dynamical variables. The two-fermion physics can be explored through this solution. The condition for the existence of bound states is examined.Comment: 21pages, Latex, 1postscript figur

A mixed-mode shell-model theory for nuclear structure studies

We introduce a shell-model theory that combines traditional spherical states, which yield a diagonal representation of the usual single-particle interaction, with collective configurations that track deformations, and test the validity of this mixed-mode, oblique basis shell-model scheme on $^{24}$Mg. The correct binding energy (within 2% of the full-space result) as well as low-energy configurations that have greater than 90% overlap with full-space results are obtained in a space that spans less than 10% of the full space. The results suggest that a mixed-mode shell-model theory may be useful in situations where competing degrees of freedom dominate the dynamics and full-space calculations are not feasible.Comment: 20 pages, 8 figures, revtex 12p

Staggering behavior of the low lying excited states of even-even nuclei in a Sp(4,R) classification scheme

We implement a high order discrete derivative analysis of the low lying collective energies of even-even nuclei with respect to the total number of valence nucleon pairs N in the framework of F- spin multiplets appearing in a symplectic sp(4,R) classification scheme. We find that for the nuclei of any given F- multiplet the respective experimental energies exhibit a Delta N=2 staggering behavior and for the nuclei of two united neighboring F- multiplets well pronounced Delta N=1 staggering patterns are observed. Those effects have been reproduced successfully through a generalized sp(4,R) model energy expression and explained in terms of the step-like changes in collective modes within the F- multiplets and the alternation of the F-spin projection in the united neighboring multiplets. On this basis we suggest that the observed Delta N=2 and Delta N=1 staggering effects carry detailed information about the respective systematic manifestation of both high order alpha - particle like quartetting of nucleons and proton (neutron) pairing interaction in nuclei.PACS number(s):21.10.Re, 21.60.FwComment: 22 pages and 6 figures changes in the figure caption

On the use of the group SO(4,2) in atomic and molecular physics

In this paper the dynamical noninvariance group SO(4,2) for a hydrogen-like atom is derived through two different approaches. The first one is by an established traditional ascent process starting from the symmetry group SO(3). This approach is presented in a mathematically oriented original way with a special emphasis on maximally superintegrable systems, N-dimensional extension and little groups. The second approach is by a new symmetry descent process starting from the noninvariance dynamical group Sp(8,R) for a four-dimensional harmonic oscillator. It is based on the little known concept of a Lie algebra under constraints and corresponds in some sense to a symmetry breaking mechanism. This paper ends with a brief discussion of the interest of SO(4,2) for a new group-theoretical approach to the periodic table of chemical elements. In this connection, a general ongoing programme based on the use of a complete set of commuting operators is briefly described. It is believed that the present paper could be useful not only to the atomic and molecular community but also to people working in theoretical and mathematical physics.Comment: 31 page