Fast recruiting clinical trials – a Utopian dream or logistical nightmare?

Randomised clinical trials that exceed anticipated recruitment rates will by definition have the necessary precision to answer the research question within the expected time, thus ensuring the timely release of data that will inform future clinical practice. In addition, the national or international momentum generated brings with it a collective sense of achievement. Such trials, however, may also identify logistical and scientific problems that researchers should be aware of and for which provision needs to be made. The logistical problems relate to the rapid identification of the extra resources required to allow continued excellence in day-to-day management and monitoring of trial governance (both in participating centres and in coordinating trials units). The scientific/clinical problems include managing issues such as unexpected toxicities and suboptimal compliance, and the lack of time available in a rapidly recruiting trial to address them. A related issue concerns the lack of time available to initiate substudies (e.g. biological substudies), the relevance of which may only become apparent as the trial progresses. Many of these challenges were highlighted by recent experience with the Cancer Research UK Taxotere as Adjuvant Chemotherapy trial

How do patients want to learn of results of clinical trials? A survey of 1431 breast cancer patients

Questionnaires were circulated to UK patients and health care professionals (HCPs) participating in the Taxotere as Adjuvant ChemoTherapy (TACT) trial in autumn 2004 asking if and how trial results, when available, should be conveyed to patients. A total of 1431 (37% of surviving UK TACT patients) returned questionnaires. In all, 30 (2%) patients did not want results. In all, 554 (40%) patients preferred to receive them via their hospital; 664 (47%) preferred results posted directly to their home, 177 (13%) preferred a letter providing a telephone number to request results. Six hundred and twelve patients thought results should come directly from the trials office. One hundred and seventy-six HCPs from 89 UK centres (86%) returned questionnaires. In all, 169 out of 176 patients (96%) thought results should be written in lay terms for patients. Seventy (41%) preferred patients to receive results via their hospital; 64 (38%) preferred a letter providing a telephone number to request results, and 32 (19%) preferred results posted directly to patients. Thirty-one HCPs (18%) thought results to patients should come directly from the trials office. A total of 868 (61%) patients thought next of kin of deceased patients should receive results, 543 (38%) did not; 47 (27%) HCPs thought they should; 118 (68%) did not

Wall slip and flow of concentrated hard-sphere colloidal suspensions

We present a comprehensive study of the slip and flow of concentrated colloidal suspensions using cone-plate rheometry and simultaneous confocal imaging. In the colloidal glass regime, for smooth, non-stick walls, the solid nature of the suspension causes a transition in the rheology from Herschel-Bulkley (HB) bulk flow behavior at large stress to a Bingham-like slip behavior at low stress, which is suppressed for sufficient colloid-wall attraction or colloid-scale wall roughness. Visualization shows how the slip-shear transition depends on gap size and the boundary conditions at both walls and that partial slip persist well above the yield stress. A phenomenological model, incorporating the Bingham slip law and HB bulk flow, fully accounts for the behavior. Microscopically, the Bingham law is related to a thin (sub-colloidal) lubrication layer at the wall, giving rise to a characteristic dependence of slip parameters on particle size and concentration. We relate this to the suspension's osmotic pressure and yield stress and also analyze the influence of van der Waals interaction. For the largest concentrations, we observe non-uniform flow around the yield stress, in line with recent work on bulk shear-banding of concentrated pastes. We also describe residual slip in concentrated liquid suspensions, where the vanishing yield stress causes coexistence of (weak) slip and bulk shear flow for all measured rates

Simple approximation for the starting-energy-independent two-body effective interaction with applications to 6Li

We apply the Lee-Suzuki iteration method to calculate the linked-folded diagram series for a new Nijmegen local NN potential. We obtain an exact starting-energy-independent effective two-body interaction for a multi-shell, no-core, harmonic-oscillator model space. It is found that the resulting effective-interaction matrix elements can be well approximated by the Brueckner G-matrix elements evaluated at starting energies selected in a simple way. These starting energies are closely related to the energies of the initial two-particle states in the ladder diagrams. The ``exact'' and approximate effective interactions are used to calculate the energy spectrum of 6Li in order to test the utility of the approximate form.Comment: 15 text pages and 2 PostScript figures (available upon request). University of Arizona preprint, Number unassigne

Implementation of Grover's Quantum Search Algorithm in a Scalable System

We report the implementation of Grover's quantum search algorithm in the scalable system of trapped atomic ion quantum bits. Any one of four possible states of a two-qubit memory is marked, and following a single query of the search space, the marked element is successfully recovered with an average probability of 60(2)%. This exceeds the performance of any possible classical search algorithm, which can only succeed with a maximum average probability of 50%.Comment: 4 pages, 3 figures, updated error discussio

Large-scale UK audit of blood transfusion requirements and anaemia in patients receiving cytotoxic chemotherapy

Cancer patients receiving cytotoxic chemotherapy often become anaemic and may require blood transfusions. A large-scale audit of patients with a variety of solid tumours receiving chemotherapy at 28 specialist centers throughout the UK was undertaken to quantify the problem. Data were available from 2719 patients receiving 3206 courses of cytotoxic chemotherapy for tumours of the breast (878), ovary (856), lung (772) or testis (213). Their mean age was 55 years (range 16–87). Overall, 33% of patients required at least one blood transfusion but the proportion varied from 19% for breast cancer to 43% for lung. Sixteen per cent of patients required more than one transfusion (7% for breast, 22% in lung). The mean proportion of patients with Hb < 11 g dl−1rose over the course of chemotherapy from 17% before the first cycle, to 38% by the sixth, despite transfusion in 33% of patients. Of the patients receiving transfusions, 25% required an inpatient admission and overnight stay. The most common symptoms reported at the time of transfusion were lethargy, tiredness and breathlessness. Further research is needed to evaluate the role of blood transfusions in patients receiving cytotoxic chemotherapy. © 2000 Cancer Research Campaig

Auxiliary potential in no-core shell-model calculations

The Lee-Suzuki iteration method is used to include the folded diagrams in the calculation of the two-body effective interaction $v^{(2)}_{\rm eff}$ between two nucleons in a no-core model space. This effective interaction still depends upon the choice of single-particle basis utilized in the shell-model calculation. Using a harmonic-oscillator single-particle basis and the Reid-soft-core {\it NN} potential, we find that $v^{(2)}_{\rm eff}$ overbinds ^4\mbox{He} in 0, 2, and $4\hbar\Omega$ model spaces. As the size of the model space increases, the amount of overbinding decreases significantly. This problem of overbinding in small model spaces is due to neglecting effective three- and four-body forces. Contributions of effective many-body forces are suppressed by using the Brueckner-Hartree-Fock single-particle Hamiltonian.Comment: 14 text pages and 4 figures (in postscript, available upon request). AZ-PH-TH/94-2

On defining the Hamiltonian beyond quantum theory

Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

TPOAb and thyroid function are not associated with breast cancer outcome: evidence from a large-scale study using data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

Background: Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives: We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Methods: TACT women >18 years old with node-positive or high-risk node-negative early breast cancer (pT1–3a, pN0–1, M0), with stored plasma (n = 1,974), taken 15.5 (median; IQR 7.0–24.0) months after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1,745/1,974; 88.4%), hormonal therapy (1,378/ 1,974; 69.8%), or trastuzumab (48/1,974; 2.4%). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), and time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results: No difference in DFS was found by TPOAb status (unadjusted hazard ratio [HR]: 0.97, 95%CI: 0.78–1.19; p = 0.75) and/or thyroid function (unadjusted HR [hypothyroid vs. euthyroid]: 1.15, 95% CI: 0.79–1.68; p = 0.46; unadjusted HR [hyperthyroid vs. euthyroid]: 1.14, 95% CI: 0.82–1.61; p = 0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered, and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions: No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-to-high-risk early breast cancer was found in the largest and longest observational study to date

The linearization of the Kodama state

We study the question of whether the linearization of the Kodama state around classical deSitter spacetime is normalizable in the inner product of the theory of linearized gravitons on deSitter spacetime. We find the answer is no in the Lorentzian theory. However, in the Euclidean theory the corresponding linearized Kodama state is delta-functional normalizable. We discuss whether this result invalidates the conjecture that the full Kodama state is a good physical state for quantum gravity with positive cosmological constant.Comment: 14 pages, statement on the corresponding Yang-Mills case correcte