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

Transcripts for transforming growth factors in human breast cancer: clinical correlates.

The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients

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

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

The large‐scale freshwater cycle of the Arctic

This paper synthesizes our understanding of the Arctic\u27s large‐scale freshwater cycle. It combines terrestrial and oceanic observations with insights gained from the ERA‐40 reanalysis and land surface and ice‐ocean models. Annual mean freshwater input to the Arctic Ocean is dominated by river discharge (38%), inflow through Bering Strait (30%), and net precipitation (24%). Total freshwater export from the Arctic Ocean to the North Atlantic is dominated by transports through the Canadian Arctic Archipelago (35%) and via Fram Strait as liquid (26%) and sea ice (25%). All terms are computed relative to a reference salinity of 34.8. Compared to earlier estimates, our budget features larger import of freshwater through Bering Strait and larger liquid phase export through Fram Strait. While there is no reason to expect a steady state, error analysis indicates that the difference between annual mean oceanic inflows and outflows (∼8% of the total inflow) is indistinguishable from zero. Freshwater in the Arctic Ocean has a mean residence time of about a decade. This is understood in that annual freshwater input, while large (∼8500 km3), is an order of magnitude smaller than oceanic freshwater storage of ∼84,000 km3. Freshwater in the atmosphere, as water vapor, has a residence time of about a week. Seasonality in Arctic Ocean freshwater storage is nevertheless highly uncertain, reflecting both sparse hydrographic data and insufficient information on sea ice volume. Uncertainties mask seasonal storage changes forced by freshwater fluxes. Of flux terms with sufficient data for analysis, Fram Strait ice outflow shows the largest interannual variability

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

The prognostic significance of transforming growth factors in human breast cancer.

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome