Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials

Fluctuations in viscous fingering

Our experiments on viscous (Saffman-Taylor) fingering in Hele-Shaw channels reveal finger width fluctuations that were not observed in previous experiments, which had lower aspect ratios and higher capillary numbers Ca. These fluctuations intermittently narrow the finger from its expected width. The magnitude of these fluctuations is described by a power law, Ca^{-0.64}, which holds for all aspect ratios studied up to the onset of tip instabilities. Further, for large aspect ratios, the mean finger width exhibits a maximum as Ca is decreased instead of the predicted monotonic increase.Comment: Revised introduction, smoothed transitions in paper body, and added a few additional minor results. (Figures unchanged.) 4 pages, 3 figures. Submitted to PRE Rapi

Picture-Hanging Puzzles

We show how to hang a picture by wrapping rope around n nails, making a polynomial number of twists, such that the picture falls whenever any k out of the n nails get removed, and the picture remains hanging when fewer than k nails get removed. This construction makes for some fun mathematical magic performances. More generally, we characterize the possible Boolean functions characterizing when the picture falls in terms of which nails get removed as all monotone Boolean functions. This construction requires an exponential number of twists in the worst case, but exponential complexity is almost always necessary for general functions.Comment: 18 pages, 8 figures, 11 puzzles. Journal version of FUN 2012 pape

Electron Spin Resonance Above Tc In Layered Manganites

We have performed electron spin resonance (ESR) and dc magnetization measurements on single crystals of La2(1-x)Sr1+2xMn2O7 up to 800 K with special emphasis on the x = 0.4 composition. The ESR linewidth shows behavior similar to that observed in the three-dimensional perovskites and above ∼500 K can be described by a universal expression ΔHpp(T)=[C/Tχ(T)]ΔHpp (∞). The linewidth and the resonance field become anisotropic below ∼500 K. The anisotropy in the resonance field is proportional to the magnetization M, and we concluded that it is intrinsic to the system. We show that demagnetization effects can explain only part of the anisotropy. The remainder arises from short-range uniaxial terms in the Hamiltonian that are associated with the crystal field and Dzialozhinsky-Moriya interactions. The anisotropy in the linewidth is attributed to the easy-plane ferromagnetic ordering, which also arises from the short-range anisotropy.631717441311744136Ruddlesden, S.N., Popper, P., (1958) Acta Crystallogr., 11, p. 54Moritomo, Y., Asamitsu, A., Kuwahara, H., Tokura, Y., (1996) Nature (London), 380, p. 141Causa, M.T., Tovar, M., Caneiro, A., Prado, F., Ibanez, G., Ramos, C.A., Butera, A., Oseroff, S.B., (1998) Phys. Rev. B, 58, p. 3233Causa, M.T., Alejandro, G., Tovar, M., Pagliuso, P.G., Rettori, C., Oseroff, S.B., Subramanian, M.A., (1999) J. Appl. Phys., 85, p. 5408Huber, D.L., Alejandro, G., Caneiro, A., Causa, M.T., Prado, F., Tovar, M., Oseroff, S.B., (1999) Phys. Rev. B, 60, p. 12155Oseroff, S.B., Moreno, N.O., Pagliuso, P.G., Rettori, C., Huber, D.L., Gardner, J.S., Sarrao, J.L., Alascio, B.R., (2000) J. Appl. Phys., 87, p. 5810Seehra, M.S., Ibrahim, M.M., Babu, V.S., Srinivasan, G., (1996) J. Phys.: Condens. Matter, 8, p. 11283Dominguez, M., Lofland, S.E., Bhagat, S.M., Raychaudhuri, A.K., Ju, H.L., Venkates, T., Greene, R.L., (1996) Solid State Commun., 97, p. 193Lofland, S.E., Kim, P., Dahiroc, P., Bhagat, S.M., Tyagi, S.D., Karabashev, S.G., Shultyatev, D.A., Mukovskii, Y., (1997) Phys. Lett. A, 233, p. 476Kimura, T., Tomioka, Y., Kuwahara, H., Asamitsu, A., Tamura, M., Tokura, Y., (1996) Science, 274, p. 1698Perring, T.G., Aeppli, G., Moritomo, Y., Tokura, Y., (1997) Phys. Rev. Lett., 78, p. 3197Zhou, J.-S., Goodenough, J.B., Mitchell, J.F., (1998) Phys. Rev. B, 58, p. 579Zhou, J.-S., Goodenough, J.B., (1998) Phys. Rev. Lett., 80, p. 2665Kelley, T.M., Argyriou, D.N., Robinson, R.A., Nakotte, H., Mitchell, J.F., Osbron, R., Jorgensen, J.D., (1998) Physica B, 241-243, p. 439Heffner, R.H., MacLaughlin, D.E., Nieuwenhuys, G.J., Kimura, T., Luke, G.M., Tokura, Y., Uemura, Y.J., (1998) Phys. Rev. Lett., 81, p. 1706Potter, C.D., Swiatek, M., Bader, S.D., Argyriou, D.N., Mitchell, J.F., Miller, D.J., Hinks, D.G., Jorgensen, J.D., (1998) Phys. Rev. B, 57, p. 72Chauvet, O., Goglio, G., Molinie, P., Corraze, B., Brohan, L., (1998) Phys. Rev. Lett., 81, p. 1102Hirota, K., Moritomo, Y., Fujioka, H., Kubota, M., Yoshizawa, H., Endoh, Y., (1998) J. Phys. Soc. Jpn., 67, p. 3380Li, J.Q., Matsui, Y., Kimura, T., Tokura, Y., (1998) Phys. Rev. B, 57, pp. R3205Kimura, T., Kumai, R., Tokura, Y., Li, J.Q., Matsui, Y., (1998) Phys. Rev. B, 58, p. 11081Hayashi, T., Miura, N., Tokunaga, M., Kimura, T., Tokura, Y., (1998) J. Phys.: Condens. Matter, 10, p. 11525Suryanarayanan, R., Dhalenne, G., Revcolevschi, A., Prellier, W., Renard, J.P., Dupas, C., Caliebe, W., Chatterji, T., (2000) Solid State Commun., 113, p. 267Kubota, M., Fujioka, H., Ohoyama, K., Hirota, K., Moritomo, Y., Yoshizawa, H., Endoh, Y., (1999) J. Phys. Chem. Solids, 60, p. 116Bhagat, S.M., Lofland, S.E., Mitchell, J.F., (1999) Phys. Lett. A, 259, p. 326Kittel, C., (1997) Introduction to Solid State Physics, , Wiley, New YorkOkochi, M., (1970) J. Phys. Soc. Jpn., 28, p. 897Victoria, C., Barker, R.C., Yelon, A., (1967) Phys. Rev. Lett., 19, p. 792Nagata, K., (1976) J. Phys. Soc. Jpn., 40, p. 1209Nagata, K., Yamamoto, I., Takano, H., Yokozawa, Y., (1977) J. Phys. Soc. Jpn., 43, p. 857. , and references thereinHuber, D.L., Seehra, M.S., (1976) Phys. Status Solidi B, 74, p. 145Stanger, J.-L., Andre, J.-J., Turek, P., Hosokoshi, Y., Tamura, M., Kinoshita, M., Rey, P., Veciana, J., (1997) Phys. Rev. B, 55, p. 8398Van Vleck, J.H., (1950) Phys. Rev., 78, p. 266Kittel, C., (1948) Phys. Rev., 73, p. 15

The effect of the annealing temperature on the local distortion of La0.67_{0.67}Ca0.33_{0.33}MnO3_3 thin films

Mn $K$-edge fluorescence data are presented for thin film samples (3000~\AA) of Colossal Magnetoresistive (CMR) La$_{0.67}$Ca$_{0.33}$MnO$_3$: as-deposited, and post-annealed at 1000 K and 1200 K. The local distortion is analyzed in terms of three contributions: static, phonon, and an extra, temperature-dependent, polaron term. The polaron distortion is very small for the as-deposited sample and increases with the annealing temperature. In contrast, the static distortion in the samples decreases with the annealing temperature. Although the local structure of the as-deposited sample shows very little temperature dependence, the change in resistivity with temperature is the largest of these three thin film samples. The as-deposited sample also has the highest magnetoresistance (MR), which indicates some other mechanism may also contribute to the transport properties of CMR samples. We also discuss the relationship between local distortion and the magnetization of the sample.Comment: 11 pages of Preprint format, 8 figures in one tar fil

Average Lattice Symmetry and Nanoscale Structural Correlations in Magnetoresistive Manganites

We report x-ray scattering studies of nanoscale structural correlations in the paramagnetic phases of the perovskite manganites La$_{0.75}$(Ca$_{0.45}$Sr$_{0.55}$)$_{0.25}$MnO$_3$, La$_{0.625}$Sr$_{0.375}$MnO$_3$, and Nd$_{0.45}$Sr$_{0.55}$MnO$_3$. We find that these correlations are present in the orthorhombic $O$ phase in La$_{0.75}$(Ca$_{0.45}$Sr$_{0.55}$)$_{0.25}$MnO$_3$, but they disappear abruptly at the orthorhombic-to-rhombohedral transition in this compound. The orthorhombic phase exhibits increased electrical resistivity and reduced ferromagnetic coupling, in agreement with the association of the nanoscale correlations with insulating regions. In contrast, the correlations were not detected in the two other compounds, which exhibit rhombohedral and tetragonal phases. Based on these results, as well as on previously published work, we propose that the local structure of the paramagnetic phase correlates strongly with the average lattice symmetry, and that the nanoscale correlations are an important factor distinguishing the insulating and the metallic phases in these compounds.Comment: a note on recent experimental work, and a new reference adde

The Structure of Nanoscale Polaron Correlations in La1.2Sr1.8Mn2O7

A system of strongly-interacting electron-lattice polarons can exhibit charge and orbital order at sufficiently high polaron concentrations. In this study, the structure of short-range polaron correlations in the layered colossal magnetoresistive perovskite manganite, La1.2Sr1.8Mn2O7, has been determined by a crystallographic analysis of broad satellite maxima observed in diffuse X-ray and neutron scattering data. The resulting q=(0.3,0,1) modulation is a longitudinal octahedral-stretch mode, consistent with an incommensurate Jahn-Teller-coupled charge-density-wave fluctuations, that implies an unusual orbital-stripe pattern parallel to the directions.Comment: Reformatted with RevTe

Anisotropic phonon conduction and lattice distortions in CMR-type bilayer manganite (La1−z_{1-z}Prz_{z})1.2_{1.2}Sr1.8_{1.8}Mn2_{2}O7_{7} (z=0,0.2,0.4 and 0.6) single crystals

We have undertaken a systematic study of thermal conductivity as a function of temperature and magnetic field of single crystals of the compound (La$_{1-z}$Pr$_{z}$)$_{1.2}$Sr$_{1.8}$Mn$_{2}$O$_{7}$ for $z$(Pr) =0.2,0.4. and 0.6. The lattice distortion due to Pr-substitution and anisotropic thermal conductivity in bilayer manganites are discussed on the basis of different relaxation models of local lattice distortions in metal and insulating states proposed by Maderda et al. The giant magnetothermal effect is scaled as a function of magnetization and discussed on the basis of a systematic variation of the occupation of the $e_g$-electron orbital states due to Pr-substitution.Comment: 7 pages, 6 figures, in press in Phys.Rev.

Universality and Critical Phenomena in String Defect Statistics

The idea of biased symmetries to avoid or alleviate cosmological problems caused by the appearance of some topological defects is familiar in the context of domain walls, where the defect statistics lend themselves naturally to a percolation theory description, and for cosmic strings, where the proportion of infinite strings can be varied or disappear entirely depending on the bias in the symmetry. In this paper we measure the initial configurational statistics of a network of string defects after a symmetry-breaking phase transition with initial bias in the symmetry of the ground state. Using an improved algorithm, which is useful for a more general class of self-interacting walks on an infinite lattice, we extend the work in \cite{MHKS} to better statistics and a different ground state manifold, namely $\R P^2$, and explore various different discretisations. Within the statistical errors, the critical exponents of the Hagedorn transition are found to be quite possibly universal and identical to the critical exponents of three-dimensional bond or site percolation. This improves our understanding of the percolation theory description of defect statistics after a biased phase transition, as proposed in \cite{MHKS}. We also find strong evidence that the existence of infinite strings in the Vachaspati Vilenkin algorithm is generic to all (string-bearing) vacuum manifolds, all discretisations thereof, and all regular three-dimensional lattices.Comment: 62 pages, plain LaTeX, macro mathsymb.sty included, figures included. also available on http://starsky.pcss.maps.susx.ac.uk/groups/pt/preprints/96/96011.ps.g

On the algebraic K-theory of the complex K-theory spectrum

Let p>3 be a prime, let ku be the connective complex K-theory spectrum, and let K(ku) be the algebraic K-theory spectrum of ku. We study the p-primary homotopy type of the spectrum K(ku) by computing its mod (p,v_1) homotopy groups. We show that up to a finite summand, these groups form a finitely generated free module over a polynomial algebra F_p[b], where b is a class of degree 2p+2 defined as a higher Bott element.Comment: Revised and expanded version, 42 pages