Long-Term Treatment of Metastatic Colorectal Cancer with Panitumumab

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. More than 30% patients present with metastases at diagnoses and will require systemic chemotherapy. In recent years many anti-EGFR targets have been developed. Among them, panitumumab, a fully human IgG2 monoclonal antibody has shown important benefits in the treatment of this disease

Albumin Yanomama-2, a ‘private’ polymorphism of serum albumin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65429/1/j.1469-1809.1974.tb01949.x.pd

Happiness Scale Interval Study. Methodological Considerations

The Happiness Scale Interval Study deals with survey questions on happiness, using verbal response options, such as ‘very happy’ and ‘pretty happy’. The aim is to estimate what degrees of happiness are denoted by such terms in different questions and languages. These degrees are expressed in numerical values on a continuous [0,10] scale, which are then used to compute ‘transformed’ means and standard deviations. Transforming scores on different questions to the same scale allows to broadening the World Database of Happiness considerably. The central purpose of the Happiness Scale Interval Study is to identify the happiness values at which respondents change their judgment from e.g. ‘very happy’ to ‘pretty happy’ or the reverse. This paper deals with the methodological/statistical aspects of this approach. The central question is always how to convert the frequencies at which the different possible responses to the same question given by a sample into information on the happiness distribution in the relevant population. The primary (cl)aim of this approach is to achieve this in a (more) valid way. To this end, a model is introduced that allows for dealing with happiness as a latent continuous random variable, in spite of the fact that it is measured as a discrete one. The [0,10] scale is partitioned in as many contiguous parts as the number of possible ratings in the primary scale sums up to. Any subject with a (self-perceived) happiness in the same subinterval is assumed to select the same response. For the probability density function of this happiness random variable, two options are discussed. The first one postulates a uniform distribution within each of the different subintervals of the [0,10] scale. On the basis of these results, the mean value and variance of the complete distribution can be estimated. The method is described, including the precision of the estimates obtained in this way. The second option assumes the happiness distribution to be described as a beta distribution on the interval [0,10] with two shape parameters (α and β). From their estimates on the basis of the primary information, the mean value and the variance of the happiness distribution in the population can be estimated. An illustration is given in which the method is applied to existing measurement results of 20 surveys in The Netherlands in the period 1990–2008. The results clarify our recommendation to apply the model with a uniform distribution within each of the category intervals, in spite of a better validity of the alternative on the basis of a beta distribution. The reason is that the recommended model allows to construct a confidence interval for the true but unknown population happiness distribution. The paper ends with a listing of actual and potential merits of this approach, which has been described here for verbal happiness questions, but which is also applicable to phenomena which are measured along similar lines

Conversion of Verbal Response Scales: Robustness Across Demographic Categories

Happiness and life satisfaction have traditionally been measured using verbal response scales, however, these verbal scales have not kept up with the present trend to use numerical response scales. A switch from a verbal scale to a numerical scale, however, causes a severe problem for trend analyses, due to the incomparability of the old and new measurements. The Reference Distribution Method is a method that has been developed recently to deal with this comparison problem. In this method use is made of a reference distribution based on responses to a numerical scale which is used to decide at which point verbally labelled response options transit from one state to another, for example from ‘happy’ to ‘very happy’. Next, for each wave of the time series in which the verbal scale is used, a population mean is estimated for the beta distribution that fits best to these transition points and the responses in this wave. These estimates are on a level that is comparable to that of the mean of the reference distribution and are appropriate for use in an extended time series based on the responses measured using a verbal and a numerical scale. In this paper we address the question of whether the transition points derived for the general population can be used for demographic categories to produce reliable, extended time series to monitor differences in trends among these categories. We conclude that this is possible and that it is not necessary to derive transition points for each demographic category separately

Mildly oxidised LDL induces more macrophage death than moderately oxidised LDL:roles of peroxidation, lipoprotein-associated phospholipase A2 and PPARgamma

AbstractDeath of macrophages and smooth muscle cells (SMC) can lead to progression of atherosclerosis. Mildly oxidised low-density lipoprotein (mildly-oxLDL) induced more overall death and apoptosis than moderately oxidised LDL, in human monocyte-macrophages (HMM). Mildly-oxLDL also induced more overall death in human SMC than did moderately-oxLDL. Mildly-oxLDL contained more hydroperoxides, but less oxysterol, malondialdehyde and negative charge than moderately-oxLDL. Specific inhibition of lipoprotein-associated phospholipase A2 (by SB222657) diminished death induction in HMM by both oxLDL types. Peroxisome proliferator-activated receptor γ (PPARγ) antagonist (GW9662) and agonist (ciglitazone) experiments suggested that non-hydrolysed, oxidised phospholipids in oxLDL activate PPARγ as a cellular defence mechanism. These results may be relevant to LDL oxidation within atherosclerotic plaques and may suggest strategies for combating atherosclerosis progression

Adalimumab and infliximab survival in patients with hidradenitis suppurativa:a daily practice cohort study

Background: Biologics are often required for the treatment of hidradenitis suppurativa (HS). However, data on the drug survival of biologics in daily practice are currently lacking. Objectives: To assess the d

Laboratory simulation of the electrodynamic interactions of a tethered satellite with an ionospheric plasma

An improved experimental set-up in the Orleans Plasma Chamber allowed investigations of the I-V characteristics of a conductive spherical body (10 cm diameter) in a plasma environment. Moreover, the influence of a transversal magnetic field at 0.6 and 1.2 G was investigated, for the first time, both on the sheath potential profile and current collection. Floating potential profiles were measured at 16 different radial distances from the test body up to 9 body radii in 8 different angular positions. The test body potential could be increased in the range from -200 V up to +100 V. Preliminary results are shown and discussed

High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting.

The tumour-associated antigen epithelial glycoprotein-2 (EGP-2) is a promising target for detection and treatment of a variety of human carcinomas. Antibodies to this antigen have been successfully used in patients for imaging of small-cell lung cancer and for adjuvant treatment of minimal residual disease of colon cancer. We describe here the isolation and complete characterization of high-affinity single-chain variable fragments (scFv) to the EGP-2 antigen. First, the binding kinetics of four murine whole antibodies directed to EGP-2 (17-1A, 323/A3, MOC-31 and MOC-161) were determined using surface plasmon resonance (SPR). The MOC-31 antibody has the lowest apparent off-rate, followed by MOC-161 and 323/A3. The V-genes of the two MOC hybridomas were cloned as scFv in a phage display vector and antigen-binding phage were selected by panning on recombinant antigen. The scFvs compete with the original hybridoma antibodies for binding to antigen and specifically bind to human carcinomas in immunohistochemistry. MOC-31 scFv has an off-rate which is better than those of the bivalent 17-1A and 323/A3 whole antibodies, providing it with an essential characteristic for tumour retention in vivo. The availability of these high-affinity anti-EGP-2 antibody fragments and of their encoding V-genes creates a variety of possibilities for their future use as tumour-targeting vehicles

Lessons to be learned from the coherent photoproduction of pseudoscalar mesons

We study the coherent photoproduction of pseudoscalar mesons---particularly of neutral pions---placing special emphasis on the various sources that put into question earlier nonrelativistic-impulse-approximation calculations. These include: final-state interactions, relativistic effects, off-shell ambiguities, and violations to the impulse approximation. We establish that, while distortions play an essential role in the modification of the coherent cross section, the uncertainty in our results due to the various choices of optical-potential models is relatively small (of at most 30%). By far the largest uncertainty emerges from the ambiguity in extending the many on-shell-equivalent representations of the elementary amplitude off the mass shell. Indeed, relativistic impulse-approximation calculations that include the same pionic distortions, the same nuclear-structure model, and two sets of elementary amplitudes that are identical on-shell, lead to variations in the magnitude of the coherent cross section by up to factors of five. Finally, we address qualitatively the assumption of locality implicit in most impulse-approximation treatments, and suggest that the coherent reaction probes---in addition to the nuclear density---the polarization structure of the nucleus.Comment: Manuscript is 27 pages long and includes 11 eps figure