The optimal method to make inferences about a linear combination of proportions

Asymptotic inferences about a linear combination of K independent binomial proportions are very frequent in applied research. Nevertheless, until quite recently research had been focused almost exclusively on cases of K≤2 (particularly on cases of one proportion and the difference of two proportions). This article focuses on cases of K>2, which have recently begun to receive more attention due to their great practical interest. In order to make this inference, there are several procedures which have not been compared: the score method (S0) and the method proposed by Martín Andrés et al. (W3) for adjusted Wald (which is a generalization of the method proposed by Price and Bonett) on the one hand and, on the other hand, the method of Zou et al. (N0) based on the Wilson confidence interval (which is a generalization of the Newcombe method). The article describes a new procedure (P0) based on the classic Peskun method, modifies the previous methods giving them continuity correction (methods S0c, W3c, N0c and P0c, respectively) and, finally, a simulation is made to compare the eight aforementioned procedures (which are selected from a total of 32 possible methods). The conclusion reached is that the S0c method is the best, although for very small samples (n i ≤ 10, ∀ i) the W3 method is better. The P0 method would be the optimal method if one needs a method which is almost never too liberal, but this entails using a method which is too conservative and which provides excessively wide CIs. The W3 and P0 methods have the additional advantage of being very easy to apply. A free programme which allows the application of the S0 and S0c methods (which are the most complex) can be obtained at http://www.ugr.es/local/bioest/Z_LINEAR_K.EXE

The two pion decay of the Roper resonance

We evaluate the two pion decay of the Roper resonance in a model where explicit re-scattering of the two final pions is accounted for by the use of unitarized chiral perturbation theory. Our model does not include an explicit $\epsilon$ or $\sigma$ scalar-isoscalar meson decay mode, instead it generates it dynamically by means of the pion re-scattering. The two ways, explicit or dynamically generated, of introducing this decay channel have very different amplitudes. Nevertheless, through interference with the other terms of the model we are able to reproduce the same phenomenology as models with explicit consideration of the $\epsilon$ meson.Comment: 17 latex pages, 11 eps figures. A few misprints corrected. A few new references. Version accepted for publication in Phys. Rev.

On the background in the γp→ω(π0γ)p\gamma p \to \omega(\pi^0\gamma) p reaction and mixed event simulation

In this paper we evaluate sources of background for the $\gamma p \to \omega p$, with the $\omega$ detected through its $\pi^0 \gamma$ decay channel, to compare with the experiment carried out at ELSA. We find background from $\gamma p \to \pi^0 \pi^0 p$ followed by decay of a $\pi^0$ into two $\gamma$, recombining one $\pi^0$ and one $\gamma$, and from the $\gamma p \to \pi^0 \eta p$ reaction with subsequent decay of the $\eta$ into two photons. This background accounts for the data at $\pi^0 \gamma$ invariant masses beyond 700 MeV, but strength is missing at lower invariant masses which was attributed to photon misidentification events, which we simulate to get a good reproduction of the experimental background. Once this is done, we perform an event mixing simulation to reproduce the calculated background and we find that the method provides a good description of the background at low $\pi^0 \gamma$ invariant masses but fakes the background at high invariant masses, making background events at low invariant masses, which are due to $\gamma$ misidentification events, responsible for the background at high invariant masses which is due to the $\gamma p \to \pi^0 \pi^0 p$ and $\gamma p \to \pi^0 \eta p$ reactions.Comment: 10 pages, 5 figure

Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma

Background: Proviral Insertion site for Moloney murine leukemia virus (PIM) kinases are overexpressed in hematologic malignancies, including multiple myeloma. Previous preclinical data from our group demonstrated the anti-myeloma effect of the pan-PIM kinase inhibitor PIM447. Methods: Based on those data, we evaluate here, by in vitro and in vivo studies, the activity of the triple combination of PIM447 + pomalidomide + dexamethasone (PIM-Pd) in multiple myeloma. Results: Our results show that the PIM-Pd combination exerts a potent anti-myeloma effect in vitro and in vivo, where it markedly delays tumor growth and prolongs survival of treated mice. Mechanism of action studies performed in vitro and on mice tumor samples suggest that the combination PIM-Pd inhibits protein translation processes through the convergent inhibition of c-Myc and mTORC1, which subsequently disrupts the function of eIF4E. Interestingly the MM pro-survival factor IRF4 is also downregulated after PIM-Pd treatment. As a whole, all these molecular changes would promote cell cycle arrest and deregulation of metabolic pathways, including glycolysis and lipid biosynthesis, leading to inhibition of myeloma cell proliferation. Conclusions: Altogether, our data support the clinical evaluation of the triple combination PIM-Pd for the treatment of patients with multiple myeloma.This work was supported by funding from Spanish FIS (PI15/00067, PI15/02156 and PI18/01600) and FEDER, AECC (GCB120981SAN), Junta de Castilla y León, Consejería de Sanidad (GRS 862/A/13 and BIO/SA05/14), Fundación Memoria de D. Samuel Solórzano Barruso of the University of Salamanca (FS/22-2015), Fundación Ramón Areces (FRA16/003), Sociedad Española de Hematología y Hemoterapia and Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León. E.M.O. was supported by an Inplant grant from IDIVAL. T.P. is supported by a grant from AECC (INVES18043PAÍN)

Quality changes and shelf-life prediction of a fresh fruit and vegetables purple smoothie

The sensory, microbial and bioactive quality changes of untreated (CTRL) and mild heat−treated (HT; 90 ºC/45 s) smoothies were studied and modelled throughout storage (5, 15 and 25 ºC). The overall acceptability was better preserved in HT samples being highly correlated (hierarchical clustering) with the flavour. The sensory quality data estimated smoothie shelf−life (CTRL/HT) of 18/55 (at 5 ºC), 4.5/12 (at 15 ºC), 2.4/5.8 (at 25 ºC) days. The yeast and moulds growth rate was lower in HT compared to CTRL while a lag phase for mesophiles/psychrophiles was observed in HT−5/15 ºC. HT and 5 ºC−storage stabilized the phenolics content. FRAP reported the best correlation (R2=0.94) with the studied bioactive compounds, followed by ABTS (R2=0.81) while DPPH was the total antioxidant capacity method with the lowest adjustment (R2=0.49). Conclusively, modelling was used to estimate the shelf−life of a smoothie based on quality retention after a short time−high temperature heat treatment that better preserved microbial and nutritional quality during storage.The financial support of this research was provided by the Ministerio Español de Economía y Competitividad MINECO (Projects AGL2013−48830−C2−1−R and AGL2013−48993−C2−1−R) and by FEDER funds. G.A. González−Tejedor thanks to Panamá Government for the scholarship to carry out his PhD Thesis. A. Garre (BES−2014−070946) is grateful to the MINECO for awarding him a pre−doctoral grant. We are also grateful to E. Esposito and N. Castillejo for their skilful technical assistance

Isocalar Roper excitation in the pp --> pp pi0 reaction close to threshold

A new mechanism for the pp --> pp pi0 reaction close to threshold is suggested coming from the isoscalar excitation of the Roper and its decay into N(pi pi)S-wave, with one of the pi0 emitted and the other one reabsorbed on the second nucleon. The mechanism can lead to important interference with other mechanisms and, together with experiment, serves to exclude large ranges of the 2pi N* decay parameters allowed by the N* partial decay widths.Comment: 11 LaTeX pages, 4 postscript figure

Maximally-localized generalized Wannier functions for composite energy bands

We discuss a method for determining the optimally-localized set of generalized Wannier functions associated with a set of Bloch bands in a crystalline solid. By ``generalized Wannier functions'' we mean a set of localized orthonormal orbitals spanning the same space as the specified set of Bloch bands. Although we minimize a functional that represents the total spread sum_n [ _n - _n^2 ] of the Wannier functions in real space, our method proceeds directly from the Bloch functions as represented on a mesh of k-points, and carries out the minimization in a space of unitary matrices U_mn^k describing the rotation among the Bloch bands at each k-point. The method is thus suitable for use in connection with conventional electronic-structure codes. The procedure also returns the total electric polarization as well as the location of each Wannier center. Sample results for Si, GaAs, molecular C2H4, and LiCl will be presented.Comment: 22 pages, two-column style with 4 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/index.html#nm_wan

Preclinical evaluation of the simultaneous inhibition of MCL-1 and BCL-2 with the combination of S63845 and venetoclax in multiple myeloma

This work was supported by the Spanish ISCIII-FIS and FEDER Funds (PI 15/00067 and PI 15/02156) and the Regional Health Council of Castilla y León (GRS 1604/A/17). EMA was supported by a grant from the Regional Education Council of Castilla y León co-financed by the European Social Fund

Chiral perturbation theory calculation for pn -> dpipi at threshold

We investigate the reaction pn -> dpipi in the framework of Chiral Perturbation Theory. For the first time a complete calculation of the leading order contributions is presented. We identify various diagrams that are of equal importance as compared to those recognized in earlier works. The diagrams at leading order behave as expected by the power counting. Also for the first time the nucleon-nucleon interaction in the initial, intermediate and final state is included consistently and found to be very important. This study provides a theoretical basis for a controlled evaluation of the non-resonant contributions in two-pion production reactions in nucleon-nucleon collisions.Comment: 24 pages, 3 figures, 3 table