Solution of the two identical ion Penning trap final state

We have derived a closed form analytic expression for the asymptotic motion of a pair of identical ions in a high precision Penning trap. The analytic solution includes the effects of special relativity and the Coulomb interaction between the ions. The existence and physical relevance of such a final state is supported by a confluence of theoretical, experimental and numerical evidence.Comment: 5 pages and 2 figure

Shear stress fluctuations in the granular liquid and solid phases

We report on experimentally observed shear stress fluctuations in both granular solid and fluid states, showing that they are non-Gaussian at low shear rates, reflecting the predominance of correlated structures (force chains) in the solidlike phase, which also exhibit finite rigidity to shear. Peaks in the rigidity and the stress distribution's skewness indicate that a change to the force-bearing mechanism occurs at the transition to fluid behaviour, which, it is shown, can be predicted from the behaviour of the stress at lower shear rates. In the fluid state stress is Gaussian distributed, suggesting that the central limit theorem holds. The fibre bundle model with random load sharing effectively reproduces the stress distribution at the yield point and also exhibits the exponential stress distribution anticipated from extant work on stress propagation in granular materials.Comment: 11 pages, 3 figures, latex. Replacement adds journal reference and addresses referee comment

Superscars in the LiNC=LiCN isomerization reaction

We demonstrate the existence of superscarring in the LiNC=LiCN isomerization reaction described by a realistic potential interaction in the range of readily attainable experimental energies. This phenomenon arises as the effect of two periodic orbits appearing "out of the blue"in a saddle--node bifurcation taking place in the dynamics of the system. Potential practical consequences of this superlocalization in the corresponding wave functions are also considered.Comment: 6 pages, 5 figures. to appear in EP

Statistical properties of acoustic emission signals from metal cutting processes

Acoustic Emission (AE) data from single point turning machining are analysed in this paper in order to gain a greater insight of the signal statistical properties for Tool Condition Monitoring (TCM) applications. A statistical analysis of the time series data amplitude and root mean square (RMS) value at various tool wear levels are performed, �nding that ageing features can be revealed in all cases from the observed experimental histograms. In particular, AE data amplitudes are shown to be distributed with a power-law behaviour above a cross-over value. An analytic model for the RMS values probability density function (pdf) is obtained resorting to the Jaynes' maximum entropy principle (MEp); novel technique of constraining the modelling function under few fractional moments, instead of a greater amount of ordinary moments, leads to well-tailored functions for experimental histograms.Comment: 16 pages, 7 figure

Impact of retrospective data verification to prepare the ICON6 trial for use in a marketing authorization application

Background: The ICON6 trial (ISRCTN68510403) is a phase III academic-led, international, randomized, three-arm, double-blind, placebo-controlled trial of the addition of cediranib to chemotherapy in recurrent ovarian cancer. It investigated the use of placebo during chemotherapy and maintenance (arm A), cediranib alongside chemotherapy followed by placebo maintenance (arm B) and cediranib throughout both periods (arm C). Results of the primary comparison showed a meaningful gain in progression-free survival (time to progression or death from any cause) when comparing arm A (placebo) with arm C (cediranib). As a consequence of the positive results, AstraZeneca was engaged with the Medical Research Council trials unit to discuss regulatory submission using ICON6 as the single pivotal trial. / Methods: A relatively limited level of on-site monitoring, single data entry and investigator’s local evaluation of progression were used on trial. In order to submit a license application, it was decided that (a) extensive retrospective source data verification of medical records against case report forms should be performed, (b) further quality control checks for accuracy of data entry should be performed and (c) blinded independent central review of images used to define progression should be undertaken. To assess the value of these extra activities, we summarize the impact on both efficacy and safety outcomes. / Results: Data point changes were minimal; those key to the primary results had a 0.47% error rate (36/7686), and supporting data points had a 0.18% error rate (109/59,261). The impact of the source data verification and quality control processes were analyzed jointly. The conclusion drawn for the primary outcome measure of progression-free survival between arm A and arm C was unchanged. The log-rank test p-value changed only at the sixth decimal place, the hazard ratio does not change from 0.57 with the exception of a marginal change in its upper bound (0.74–0.73) and the median progression-free survival benefit from arm C remained at 2.4 months. Separately, the blinded independent central review of progression scans was performed as a sensitivity analysis. Estimates and p values varied slightly but overall demonstrated a difference in arms, which is consistent with the initial result. Some increases in toxicity were observed, though these were generally minor, with the exception of hypertension. However, none of these increases were systematically biased toward one arm. / Conclusion: The conduct of this pragmatic, academic-sponsored trial was sufficient given the robustness of the results, shown by the results remaining largely unchanged following retrospective verification despite not being designed for use in a marketing authorization. The burden of such comprehensive retrospective effort required to ensure the results of ICON6 were acceptable to regulators is difficult to justify

Solvable three-state model of a driven double-well potential and coherent destruction of tunneling

A simple model for a particle in a double well is derived from discretizing its configuration space. The model contains as many free parameters as the original system and it respects all the existing symmetries. In the presence of an external periodic force both the continuous system and the discrete model are shown to possess a generalized time-reversal symmetry in addition to the known generalized parity. The impact of the driving force on the spectrum of the Floquet operator is studied. In particular, the occurrence of degenerate quasienergies causing coherent destruction of tunneling is discussed—to a large extent analytically—for arbitrary driving frequencies and barrier heights

ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy

BACKGROUND: Two novel biological agents-cediranib targeting angiogenesis, and olaparib targeting DNA repair processes-have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse. STUDY HYPOTHESIS: Maintenance therapy with cediranib and olaparib in combination is associated with improved patient outcomes compared with olaparib alone. TRIAL DESIGN: International phase III randomized controlled trial. Following a response to platinum-based chemotherapy patients are randomized 1:1 to either oral olaparib and cediranib (intervention arm) or oral olaparib alone (control arm). MAJOR INCLUSION CRITERIA: Patients with a known diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after first-line platinum-based chemotherapy, who have responded to second-line platinum-based chemotherapy. PRIMARY ENDPOINTS: Progression-free and overall survival. Co-primary endpoints to be assessed using a fixed-sequence gatekeeping approach: (1) progression-free survival, all patients; (2) progression-free survival, BRCA wild type; (3) overall survival, all patients; (4) overall survival, BRCA wild type. SAMPLE SIZE: 618 patients will be recruited. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03278717

Clarifying the structure of low-lying states in Br-72

The spins and parities of low-lying states in Br72 populated in the β decay of Kr72 have been studied via conversion electron spectroscopy. The measurements were carried out at ISOLDE using a miniorange spectrometer with Si(Li) and HPGe detectors for electrons and γ ray detection. Results of the conversion coefficients corresponding to transitions deexciting 12 levels in Br72 are reported. The multipolarities of the transitions are deduced and the spins and parities of the levels involved are discussed. From the multipolarities of the most intense transitions to the ground state, the spin and parity of the Br72 ground state have been definitely established as 1+. The spin of the 101.2-keV isomeric state is determined to be 3-. The level scheme is compared with mean-field and shell-model calculations and oblate deformation for the Br72 ground state is deduced. No E0 transitions have been found in Br72. E0 transitions in the neighboring isobaric nuclei, Se72 and Ge72, have also been studie

The role of humic non-exchangeable binding in the promotion of metal ion

Metal ions form strong complexes with humic substances. When the metal ion is first complexed by humic material, it is bound in an ‘exchangeable’ mode. The metal ion in this fraction is strongly bound, however, if the metal–humic complex encounters a stronger binding site on a surface, then the metal ion may dissociate from the humic substance and be immobilised. However, over time, exchangeably-bound metal may transfer to a ‘non-exchangeable’ mode. Transfer into this mode and dissociation from it are slow, regardless of the strength of the competing sink, and so immobilisation may be hindered. A series of coupled chemical transport calculations has been performed to investigate the likely effects of non-exchangeable binding upon the transport of metal ions in the environment. The calculations show that metal in the nonexchangeable mode will have a significantly higher mobility than that in the exchangeable mode. The critical factor is the ratio of the non-exchangeable first-order dissociation rate constant and the residence time in the groundwater column, metal ion mobility increasing with decreasing rate constant. A second series of calculations has investigated the effect of the sorption to surfaces of humic/metal complexes on the transport of the non-exchangeably bound metal. It was found that such sorption may reduce mobility, depending upon the humic fraction to which the metal ion is bound. For the more weakly sorbing humic fractions, under ambient conditions (humic concentration etc.) the non-exchangeable fraction may still transport significantly. However, for the more strongly sorbed fractions, the non-exchangeable fraction has little effect upon mobility. In addition to direct retardation, sorption also increases the residence time of the nonexchangeable fraction, giving more time for dissociation and immobilisation. The nonexchangeable dissociation reaction, and the sorption reaction have been classified in terms of two Damkohler numbers, which can be used to determine the importance of chemical kinetics during transport calculations. These numbers have been used to develop a set of rules that determine when full chemical kinetic calculations are required for a reliable prediction, and when equilibrium may be assumed, or when the reactions are sufficiently slow that they may be ignored completely

The relation between media promotions and service volume for a statewide tobacco quitline and a web-based cessation program

<p>Abstract</p> <p>Background</p> <p>This observational study assessed the relation between mass media campaigns and service volume for a statewide tobacco cessation quitline and stand-alone web-based cessation program.</p> <p>Methods</p> <p>Multivariate regression analysis was used to identify how weekly calls to a cessation quitline and weekly registrations to a web-based cessation program are related to levels of broadcast media, media campaigns, and media types, controlling for the impact of external and earned media events.</p> <p>Results</p> <p>There was a positive relation between weekly broadcast targeted rating points and the number of weekly calls to a cessation quitline and the number of weekly registrations to a web-based cessation program. Additionally, print secondhand smoke ads and online cessation ads were positively related to weekly quitline calls. Television and radio cessation ads and radio smoke-free law ads were positively related to web program registration levels. There was a positive relation between the number of web registrations and the number of calls to the cessation quitline, with increases in registrations to the web in 1 week corresponding to increases in calls to the quitline in the subsequent week. Web program registration levels were more highly influenced by earned media and other external events than were quitline call volumes.</p> <p>Conclusion</p> <p>Overall, broadcast advertising had a greater impact on registrations for the web program than calls to the quitline. Furthermore, registrations for the web program influenced calls to the quitline. These two findings suggest the evolving roles of web-based cessation programs and Internet-use practices should be considered when creating cessation programs and media campaigns to promote them. Additionally, because different types of media and campaigns were positively associated with calls to the quitline and web registrations, developing mass media campaigns that offer a variety of messages and communicate through different types of media to motivate tobacco users to seek services appears important to reach tobacco users. Further research is needed to better understand the complexities and opportunities involved in simultaneous promotion of quitline and web-based cessation services.</p