Conflicts of Interest and Outcomes of Cardiovascular Trials.

Conflicts of interests have long been recognized as potential sources of influence in the conduct and reporting of clinical trials. This controversy was again rekindled after the publication of the latest statin guidelines and a series of studies regarding competing interests in leading medical journals. We investigate the association between declared author conflicts and the outcomes of large cardiovascular trials. We searched the Medline (PubMed) database to identify "phase 2" and "phase 3" clinical trials using the search term "cardiovascular" over the past decade using "10 years" as the filter. We perceived the competing interest as present regardless of the nature such as consulting fees, honoraria, travel imbursements, stock holding, and employment. Of the 699 titles retrieved, 114 studies met the inclusion criteria. Nearly 80% of studies had at least a single author with competing interests. The 114 studies had a total of 1,433 investigators, of which 725 had declared conflicts of interests (50.6%). A total of 66 studies (58%) had half or >50 percent of investigators who had some conflicts of interests. Of these studies, 54 studies had favorable outcomes and only 12 had unfavorable outcomes (p <0.001). Among the type of competing interests, consulting or personal fees was the most common present in 58 investigators (51%). This was followed by research grants present in 55 the researchers (48%). Among 25 (22%) studies, at least one investigator reported stakes in the industry, of which only 2 studies had unfavorable outcomes for the intervention being investigated. Just 1 of the 25 clinical trials with a sample size of >1,000 had no investigators with competing interests. In conclusion, authors conflicts are associated with favorable outcomes in cardiovascular outcome trials.

Ecological And Metabolic Studies On Free-Living Nematodes From An Estuarine Mud-Flat

Nematodes from a mud-flat in the river Lynher estuary, Cornwall, U.K., have a population density ranging between 8 and 9 × 106 m−2 in the winter months, corresponding to a dry weight of 1·4 and 1·6 g m−2. They reach a peak abundance of 22·86 × 106 m−2 (3·4 g) in May. About 40 species are present, and the species composition remained seasonally stable over the period of study. Analysis of age-structure suggests that the major species have continuous asynchronous reproduction. Respiration rates of 16 species have been determined at 20 °C using Cartesian diver respirometry. For five species, respiration/body size regressions were obtained in the form log10R = log10a+b log10V, where R = respiration in nl O2 ind−1 h−1 and V = body volume in nl: Mesotheristus setosus (log10a = −0·04,b = 0·74), Sphaerolaimus hirsutus (log10a = 0·11, b = 0·68), Axonolaimus paraspinosus (log10a = 0·00, b = 0·79), Metachromadora vivipara (log10a = −0·59, b = 1·07), Praeacanthonchus punctatus (log10a = 0·00, b = 0·55). For the remaining 11 species, several animals were used in each diver and, by assuming b = 0·75, log10a′ values were calculated: Viscosia viscosa (log10a′ = 0·188), Innocuonema tentabundum (−0·012), Ptycholaimellus ponticus (−0·081), Odontophora setosa (−0·092), Sphaerolaimus balticus (−0·112), Dichromadora cephalata (−0·133), Atrochromadora microlaima (−0·142), Cylindrotheristus normandicus (−0·150), Terschellingialongicaudata (−0·170), Sabatieria pulchra (−0·197), Terschellingia communis (−0·277). These values are compared with recalculated values for other species from the literature. Annual respiration of the nematode community is 28·01 O2 m−2, equivalent to 11·2 g carbon metabolised. Community respiration is compared with figures from N. American saltmarshes. At 20 °C, a respiration of about 61 O2 m−2 year−1 g−1 wet weight of nematodes appears to be typical. Annual production is estimated to be 6·6 g C m−2. The correlation between feeding-group, body-size, habitat and the repiration rate of individual species is discussed.

Development of a rapid colorimetric time-kill assay for determining the in vitro activity of ceftazidime and tobramycin in combination against Pseudomonas aeruginosa

It is standard clinical practice to use a combination of two or more antimicrobial agents to treat an infection caused by Pseudonionas aeruginosa. The antibiotic combinations are usually selected empirically with methods to determine the antimicrobial effect of the combination such as the time-kill assay rarely used as they are time-consuming and labour intensive to perforin. Here, we report a modified time-kill assay, based on the reduction of the tetrazolium salt, 2,3-bis[2-methyloxy-4-nitro-5-sulfopheny1]-2H-tetrazolium-5-carboxanilide (XTT), that allows simple, inexpensive and more rapid determination of the in vitro activity of antibiotic combinations against P aeruginosa. The assay was used to determine the in vitro activity of ceftazidime and tobramycin in combination against P. aertiginosa isolates from cystic fibrosis patients and the results obtained compared with those from conventional viable count time-kill assays. There was good agreement in interpretation of results obtained by the XTT and conventional viable count assays, with similar growth curves apparent and the most effective concentration combinations determined by both methods identical for all isolates tested. The XTT assay clearly indicated whether an antibiotic combination had a synergistic, indifferent or antagonistic effect and could, therefore, provide a useful method for rapidly determining the activity of a large number of antibiotic combinations against clinical isolates. (C) 2004 Elsevier B.V. All rights reserved.

The development and validation of liquid chromatography method for the simultaneous determination of metformin and glipizide, gliclazide, glibenclamide or glimperide in plasma

This article describes the development of SPE and HPLC methods for the simultaneous determination of metformin and glipizide, gliclazide, glibenclamide or glimperide in plasma. Several extraction and HPLC methods have been described previously for the determination of each of these analytes in plasma separately. The simultaneous determination of these analytes is important for the routine monitoring of diabetic patients who take combination medications and for studying the pharmacokinetics of the combined dosage forms. In addition this developed method can serve as a standard method for the plasma determination of these analytes therefore saving time, effort and money. The recoveries of the developed methods were found to be between 76.3% and 101.9%. The limits of quantification were between 5 and 22.5 ng/ml. The intraday and interday precision (measured by coefficient of variation, CV%) was always less than 9%. The accuracy (measured by relative error %) was always less than 12%. Stability analysis showed that all analytes are stable for at least 3 months when stored at -70degreesC. (C) 2004 Elsevier B.V. All rights reserved.

Theory of the near K-edge structure in electron energy loss spectroscopy

Arguments are given that lead to a formalism for calculating near K-edge structure in electron energy loss spectroscopy (EELS). This is essentially a one electron picture, while many body effects may be introduced at different levels, such as the local density approximation to density functional theory or the GW approximation to the electron self-energy. Calculations are made within the all electron LMTO scheme in crystals with complex atomic and electronic structures, and these are compared with experiment. (c) 2004 Elsevier B.V. All rights reserved.

Electron/positron collisions with positronium

We report results for e(+/-)-Ps(Is) scattering in the energy range up to 80 eV calculated in 9-state and 30-state coupled pseudostate approximations. Cross-sections are presented for elastic scattering, ortho-para conversion, discrete excitation, ionization and total scattering. Resonances associated with the Ps(n = 2) threshold are also examined and their positions and widths determined. Very good agreement is obtained with the variational calculations of Ward et al. [J. Phys. B 20 (1987) 127] below 5.1 eV. (C) 2004 Elsevier B.V. All rights reserved.

Positronium formation in positron-noble gas collisions

Distorted-wave Born approximation calculations for Ps formation in positron impact on He, Ne, Ar, Kr and Xe are reported for the energy range up to 200 eV. Capture into the n = 1, 2 and 3 states of Ps is calculated explicitly and 1/n(3) scaling is used to estimate capture into states with n > 3. The calculations for the heavier noble gases allow for capture not only from the outer np(6) shell of the atom but also from the first inner ns(2) shell. However, the inner shell capture is found to be very small. Although by no means unambiguous, the calculations provide some support to the conjecture of Larrichia et al. [J. Phys. B 35 (2002) 2525] that the double peak and shoulder structures observed experimentally for Ps formation in Ar, Kr and Xe arise from formation in excited states. (C) 2004 Elsevier B.V. All rights reserved.

Thickness independence of true phase transition temperatures in barium strontium titanate films

The functional properties of two types of barium strontium titanate (BST) thin film capacitor structures were studied: one set of structures was made using pulsed-laser deposition (PLD) and the other using chemical solution deposition. While initial observations on PLD films looking at the behavior of T-m (the temperature at which the maximum dielectric constant was observed) and T-c(*) (from Curie-Weiss analysis) suggested that the paraelectric-ferroelectric phase transition was progressively depressed in temperature as BST film thickness was reduced, further work suggested that this was not the case. Rather, it appears that the temperatures at which phase transitions occur in the thin films are independent of film thickness. Further, the fact that in many cases three transitions are observable, suggests that the sequence of symmetry transitions that occur in the thin films are the same as in bulk single crystals. This new observation could have implications for the validity of the theoretically produced thin film phase diagrams derived by Pertsev [Phys. Rev. Lett. 80, 1988 (1998)] and extended by Ban and Alpay [J. Appl. Phys. 91, 9288 (2002)]. In addition, the fact that T-m measured for virgin films does not correlate well with the inherent phase transition behavior, suggests that the use of T-m alone to infer information about the thermodynamics of thin film capacitor behavior, may not be sufficient. (C) 2004 American Institute of Physics.