Statistical Analyses of Mutually Exclusive Competing Risks in Neonatal Studies

Following the well-established approach on how to deal with competing risks in the situation of time-to-event endpoints, cumulative incidences have to be used to analyse each single category of an outcome in the situation of competing risks without a time-to-event structure as well. This can be easily done by applying a simple chi-square test.Nevertheless, these categorial outcomes are usually combined to get a composed dichotomous outcome to face the problem on how to deal with a significant chi-square omnibus test in the situation of more than 1 df, i.e. > 2x2 tables.The aim of this report is to question the practice of combined, i.e. composed dichotomized, endpoints because important information is lost and the real effect of interest in confirmatory phase III studies may only become apparent in explorative secondary analyses.It is shown – by using hypothetical data and by recalculation of published phase III studies' results – how the use of a chi-square omnibus test and the scarcely known post-hoc testing answers the real question of interest within one primary confirmatory analysis. This method reveals insight into the actual effect of a new treatment or therapy on the event of interest in the presence of a mutually exclusive competing risk

Neurotoxicity of Ortho-Phthalates: Recommendations for Critical Policy Reforms to Protect Brain Development in Children

Robust data from longitudinal birth cohort studies and experimental studies of perinatally exposed animals indicate that exposure to ortho-phthalates can impair brain development and increase risks for learning, attention, and behavioral disorders in childhood. This growing body of evidence, along with known adverse effects on male reproductive tract development, calls for immediate action. Exposures are ubiquitous; the majority of people are exposed to multiple ortho-phthalates simultaneously. We thus recommend that a class approach be used in assessing health impacts as has been done with other chemical classes. We propose critically needed policy reforms to eliminate ortho-phthalates from products that lead to exposure of pregnant women, women of reproductive age, infants, and children. Specific attention should be focused on reducing exposures among socially vulnerable populations such as communities of color, who frequently experience higher exposures. Ortho-phthalates are used in a vast array of products and elimination will thus necessitate a multipronged regulatory approach at federal and state levels. The fact that manufacturers and retailers have already voluntarily removed ortho-phthalates from a wide range of products indicates that this goal is feasible

Large non-Gaussianity from two-component hybrid inflation

We study the generation of non-Gaussianity in models of hybrid inflation with two inflaton fields, (2-brid inflation). We analyse the region in the parameter and the initial condition space where a large non-Gaussianity may be generated during slow-roll inflation which is generally characterised by a large f_NL, tau_NL and a small g_NL. For certain parameter values we can satisfy tau_NL>>f_NL^2. The bispectrum is of the local type but may have a significant scale dependence. We show that the loop corrections to the power spectrum and bispectrum are suppressed during inflation, if one assume that the fields follow a classical background trajectory. We also include the effect of the waterfall field, which can lead to a significant change in the observables after the waterfall field is destabilised, depending on the couplings between the waterfall and inflaton fields.Comment: 16 pages, 6 figures; v2: comments and references added, typos corrected, matches published versio

A Full PFPF Shell Model Study of a~=~48 Nuclei

Exact diagonalizations with a minimally modified realistic force lead to detailed agreement with measured level schemes and electromagnetic transitions in $^{48}$Ca, $^{48}$Sc, $^{48}$Ti, $^{48}$V, $^{48}$Cr and $^{48}$Mn. Gamow-Teller strength functions are systematically calculated and reproduce the data to within the standard quenching factor. Their fine structure indicates that fragmentation makes much strength unobservable. As a by-product, the calculations suggest a microscopic description of the onset of rotational motion. The spectroscopic quality of the results provides strong arguments in favour of the general validity of monopole corrected realistic forces, which is discussed.Comment: 30 pages, LaTeX with epsf.sty, 14 Postscript figures included and compressed using uufiles. Completely new version of previous preprint nucl-th/9307001. FTUAM-93/01, CRN/PT 93-3

Clustering of venous thrombosis events at the start of tamoxifen therapy in breast cancer: A population-based experience

Introduction: The epidemiology of tamoxifen and venous thromboembolism (VTE) is not well understood, and most data on tamoxifen toxicity are from adjuvant clinical trials. This study examined the relationship between the duration of tamoxifen use in female patients with breast cancer and the risk of VTE in a large population-based setting. Materials and Methods: Retrospective electronic data extraction on tamoxifen utilization was undertaken among a cohort of 3572 women with breast cancer seen at Marshfield Clinic between January 1, 1994 and June 31, 2009. Observational follow-up extended until February, 2010. Results: On initial exposure to tamoxifen, women had a clustering of VTE events. Cox proportional hazards regression, adjusting for multiple clinically-important covariates including age, body mass index, cancer stage, and concurrent diabetes, demonstrated that as use of tamoxifen continued in those without earlier VTE events, risk of subsequent VTE gradually increased, albeit at a lower rate (hazard ratio per year of tamoxifen duration = 1.225, P < 0.0001). Conclusions: In our study population, initiating tamoxifen coincided with an initial clustering of VTE events, with risks due specifically to tamoxifen, increasing during continued exposure. Evidence suggested that the VTE clustering occurred in high risk individuals at initiation of tamoxifen therapy. Careful selection of patients for whom tamoxifen therapy is appropriate based on susceptibility to VTE is thus required prior to initiation of therapy

CUORE: A Cryogenic Underground Observatory for Rare Events

CUORE is a proposed tightly packed array of 1000 TeO2 bolometers, each being a cube 5 cm on a side with a mass of 760 g. The array consists of 25 vertical towers, arranged in a square of 5 towers by 5 towers, each containing 10 layers of 4 crystals. The design of the detector is optimized for ultralow-background searches: for neutrinoless double beta decay of 130Te (33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals 3x3x6 cm3 of 340 g has been completed, and a single CUORE tower is being constructed as a smaller scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.Comment: 39 pages, 12 figures, submitted to NI

Ab initio atomistic thermodynamics and statistical mechanics of surface properties and functions

Previous and present "academic" research aiming at atomic scale understanding is mainly concerned with the study of individual molecular processes possibly underlying materials science applications. Appealing properties of an individual process are then frequently discussed in terms of their direct importance for the envisioned material function, or reciprocally, the function of materials is somehow believed to be understandable by essentially one prominent elementary process only. What is often overlooked in this approach is that in macroscopic systems of technological relevance typically a large number of distinct atomic scale processes take place. Which of them are decisive for observable system properties and functions is then not only determined by the detailed individual properties of each process alone, but in many, if not most cases also the interplay of all processes, i.e. how they act together, plays a crucial role. For a "predictive materials science modeling with microscopic understanding", a description that treats the statistical interplay of a large number of microscopically well-described elementary processes must therefore be applied. Modern electronic structure theory methods such as DFT have become a standard tool for the accurate description of individual molecular processes. Here, we discuss the present status of emerging methodologies which attempt to achieve a (hopefully seamless) match of DFT with concepts from statistical mechanics or thermodynamics, in order to also address the interplay of the various molecular processes. The new quality of, and the novel insights that can be gained by, such techniques is illustrated by how they allow the description of crystal surfaces in contact with realistic gas-phase environments.Comment: 24 pages including 17 figures, related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Astrophysical Axion Bounds

Axion emission by hot and dense plasmas is a new energy-loss channel for stars. Observational consequences include a modification of the solar sound-speed profile, an increase of the solar neutrino flux, a reduction of the helium-burning lifetime of globular-cluster stars, accelerated white-dwarf cooling, and a reduction of the supernova SN 1987A neutrino burst duration. We review and update these arguments and summarize the resulting axion constraints.Comment: Contribution to Axion volume of Lecture Notes in Physics, 20 pages, 3 figure

Recent searches for solar axions and large extra dimensions

We analyze the data from two recent experiments designed to search for solar axions within the context of multidimensional theories of the Kaluza-Klein type. In these experiments, axions were supposed to be emitted from the solar core, in M1 transitions between the first excited state and the ground state of 57Fe and 7Li. Because of the high multiplicity of axionic Kaluza-Klein states which couple with the strength of ordinary QCD axions, we obtain much more stringent experimental limits on the four-dimensional Peccei-Quinn breaking scale f_{PQ}, compared with the solar QCD axion limit. Specifically, for the 57Fe experiment, f_{PQ}>1x10^6 GeV in theories with two extra dimensions and a higher-dimensional gravitational scale M_H of order 100 TeV, and f_{PQ}>1x10^6 GeV in theories with three extra dimensions and M_H of order 1 TeV (to be compared with the QCD axion limit, f_{PQ}>8x10^3 GeV). For the 7Li experiment, f_{PQ}>1.4x10^5 GeV and 3.4x10^5 GeV, respectively (to be compared with the QCD axion limit, f_{PQ}>1.9x10^2 GeV). It is an interesting feature of our results that, in most cases, the obtained limit on f_{PQ} cannot be coupled with the mass of the axion, which is essentially set by the (common) radius of the extra dimensions.Comment: 4 pages, revtex 4, minor changes, version accepted by PR

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ