Characteristics of moving visual scenes influencing spatial orientation

A visual display rotating in a frontal plane induces effects equivalent to a change in the apparent direction of gravity. Magnitude of visual tilt was measured as a function of time from onset of rotation, velocity of rotation, and area and retinal location of the stimulating field. The major part of the tilt occurs within 30 sec from onset of stimulation. It increases with angular velocity, but independently of area and location of field, up to about 30 to 40° of rotation per sec and then levels off. Tilt increases with field size but the effect of thin ring-fields increases with retinal eccentricity. The interaction of visual and non-visual determinants of the induced effects is discussed.     

Kinetik der radikalischen polymerisation und copolymerisation von N-vinyl-N-methylacetamid

In order to get information on the kinetics of free radical polymerization of N-vinyl-N-methylacetamide (VIMA) polymerizations of the purified monomer were performed in dilatometers using the temperature range from 25 to 70°C, monomer concentrations of 10 to 100% in methanol, and initiation either by γY-irradiation or by radical initiators. Molecular weight meassurements of the polymer were calibrated by light scattering determinations of M_w according to the following equation at 30 °C in methanol: [η]/(ml/g) = 5,02 · 10^?3 · M_w^0,7946. Normal kinetics of free radical polymerization were found to be valid and Arrhenius parameters were calculated for the ratio k_p²/k_t of the propagation rate constant k_p and the termination rate constant k_t as well as for the monomer transfer constant C_M and for the efficiency of initiation f. For copolymerizations of N-vinyl-N-methylacetamide with different comonomers the mean Q-e-values were calculated as follows: Q_VIMA ? 0,06; e_VIMA ? ? 1,8.     

Eine neue methode zur ermittlung kinetischer und kalorischer daten einer radikalischen copolymerisation, 2. Verbesserte auswertungsmethode am beispiel des systems 2-hydroxyethylmethacrylat/methylmethacrylat

The monomer reactivity ratios and the ratio of the rate constants of termination in the 2-hydroxyethyl methacrylate/methyl methacrylate system were measured by differential thermal analysis. The data for the monomer reactivity ratios agree well with data calculated from the Q-e scheme.     

Complementary laminar terminations of afferents to area 17 originating in area 18 and in the lateral geniculate nucleus in squirrel monkey

The projections from area 18 and the lateral geniculate nucleus onto area 17 of the squirrel monkey (Saimiri) were investigated with retrograde (horseradish peroxidase) and anterograde (tritiated proline) labelling techniques, and the (Fink-Heimer) silver impregnation method for degenerating axons and their terminals. The association fibers from area 18 terminated in all layers of area 17 except in layer IV and in the lower aspect of layer IIIc. The greatest number of terminals were in layers I, V and VI. The bulk of geniculocortical fibers terminated in layer IV and the lower aspect of layer IIIc; a minority of the geniculocortical fibers terminated in layer VI and the lower aspect of layer IIIb. Thus, the majority of fibers from the two sources investigated terminate in a complementary laminar fashion in area 17. The portion of area 17 on the lateral surface of the hemisphere, where the central visual field is represented, received a less dense projection from the geniculate nucleus than the striate cortex in the calcarine fissure, where the peripheral visual field is represented. Ocular dominance columns were not apparent in the striate cortex. No evidence was found that the lateral geniculate nucleus projects to area 18. The results of combined injections of horseradish peroxidase and tritiated proline in area 17 indicated a point-to-point reciprocity between area 17 and the ipsilateral lateral geniculate nucleus.     

Pharmacokinetics of gemcitabine combined with trastuzumab in patients with advanced breast cancer

BACKGROUND: Combining the monoclonal antibody trastuzumab (TMAB) with chemotherapy is a new strategy in treatment of advanced breast cancer in HER+++ overexpressing patients. PATIENTS AND METHODS: The disposition of gemcitabine has been investigated in 8 breast cancer patients (prospective cross-over design). Gemcitabine was administered as a 30-min i.v. infusion (1,000 mg/m(2) in 250 ml) on day 1 weekly for 3 weeks. On day 2 TMAB was infused with a loading dose of 4 mg/kg (90-min infusion) followed by a weekly maintenance dose of 2 mg/kg (30-min infusion). Pharmacokinetic analysis was performed after the first (= MONO) and after the third gemcitabine infusion (= TMAB). RESULTS: Cmax was 22.2 microg/ml (t(max) = 24 min) in the MONO and 24.6 microg/ml (t(max) = 23 min) in the TMAB schedule. Gemcitabine distributed rapidly from plasma within a few minutes and was eliminated with a t1/2el of about 80 min in both arms of the study. The metabolite difluorodeoxyuridine (dFdU) appeared in plasma with t1/2appin = 12.8 min (MONO) or t1/2appin = 10.2 min (TMAB) reaching a mean peak concentration of 35.9 microg/ml (MONO) or 30.4 microg/ml (TMAB), respectively. CONCLUSION: The results gave evidence that TMAB does not affect the disposition of gemcitabine.     

Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors

The perturbations of the cytokine signaling pathway play an important role in lymphoid/hematopoietic tumors. Aberrant promoter methylation is the major mechanism of gene silencing in tumors. We examined 150 lymphoid/hematopoietic tumors or potential premalignant specimens, 55 control specimens and 12 EBV-transformed B lymphoblastoid cultures and 10 lymphoma/leukemia (L/L) or multiple myeloma (MM) cell lines for the methylation (and, in cell lines, of the expression status) of three genes involved in the cytokine signaling pathway. The genes were: SHP1, a protein tyrosine phosphatase; SYK, a protein kinase; and SOCS1, a suppressor of cytokine signaling. Our major findings were: (1) one or more of the three genes was frequently methylated in L/L and MM cell lines and there was good concordance (90-100%) between methylation and loss of gene expression; (2) treatment of L/L cell lines with a demethylating agent resulted in re-expression of SHP1 protein and downregulation of phosphorylated STAT3 in L/L cell lines; (3) all 55 control specimens and the lymphoblastoid cultures were negative for methylation of the three genes; (4) non-Hodgkin's lymphomas (100%), and leukemias (94%) had almost universal methylation of SHP1 and relatively less frequent (<30%) methylation of SOCS1 and SYK; (5) MM and monoclonal gammopathy of unknown significance (MGUS) had infrequent methylation of SHP1 (<20%), and occasional methylation of SOCS1 and SYK; and (6) comparable methylation frequencies for SOCS1 were observed in MM and MGUS, suggesting that SOCS1 methylation is an early event in MM pathogenesis. At least one gene was methylated in 119 of 130 (93%) of the malignant and 12 of 20 (60%) of the MGUS samples. Our findings demonstrate that the perturbations of cytokine signaling via silencing of these three genes are almost universal in lymphoid/hematopoietic tumors but the patterns of gene methylated for L/L and plasma cell dyscrasias are different.     

Assessment of the value of confirming responses in clinical trials in oncology

The requirement for a second assessment to confirm initial tumour response is required by all response guidelines. Its rationale, however, is not clear. We have conducted this study to compare validity of response rate assessment determined with and without secondary confirmation. Using specified criteria, nine trials of one single cytotoxic drug including 416 patients were selected from a pharmaceutical database. Objective response rates were determined by a single determination and by two separate determinations. 81 responses (19.5%, [15.8-23.6%]) were scored by the confirmation method and 97 responses (23.3% [19.3-27.7%]) by the no-confirmation method. The Kappa (kappa) coefficient of 0.89 indicates good agreement between both methods. This is the first study that systematically compares response rates calculated with and without performing response confirmation. Results show good agreement between both methods. We suggest that assessing response without confirmation may be the preferred method. These results should be confirmed by additional studies in a variety of cancer settings.     

Biological surrogate end-points in cancer trials: potential uses, benefits and pitfalls

New technologies have led to the development of an increasing number of targeted therapies and interest in combining these with conventional therapy to provide individualised patient treatments. New drug or treatment regimens must, however, undergo rigorous testing under strictly controlled conditions before they can be adopted as standard. This can be expensive, time-consuming and inefficient. Surrogate end-points have been proposed as an alternative, which could be measured earlier or more conveniently than true end-points. The aim of this paper is to review the definition, advantages, disadvantages and potential pitfalls of biological surrogate end-points in the context of cancer treatment.