Search Results - (Author, Cooperation:T. Henning)

2014-01-31

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

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Natural Sciences in General

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2013-02-01

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

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2014-04-12

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

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Chemistry and Pharmacology

Computer Science

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2015-10-10

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

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2011-11-18

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

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1476-4687

Nature Archives 1869 - 2009

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

[Auszug] Sulphur is depleted in cold dense molecular clouds with embedded young stellar objects, indicating that most of it probably resides in solid grains. Iron sulphide grains are the main sulphur species in cometary dust particles, but there has been no direct evidence for FeS in astronomical ...

Electronic Resource

1350-4495

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Physics

Electronic Resource

1350-4495

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Physics

Electronic Resource

1572-8722

Springer Online Journal Archives 1860-2000

Law

Abstract This paper analyses some of the rhetorical and linguistic features of two judges' summations to two different juries in a criminal case that was tried twice in the Tasmanian Criminal Court. In the first trial, the jury failed to reach a verdict upon a number of counts in the indictment. In the second trial, the jury returned guilty verdicts on all counts. The purpose of this paper is to cast light upon how the linguistic and rhetorical features observed in the summations lent colour or weight to a particular interpretation of the events tried. The paper argues that the judge's summing up is part of the persuasive process of the criminal trial and that judges do present a version of the facts to the jury, deploying various language strategies to construct and communicate that version. The analysis focuses solely upon the judges' summing up of the evidence and the facts. It does not deal with directions or determinations concerning the law. Three major differences between the summations are considered: their distinct thematic approaches to the factual issues, the disparate levels of assistance they provide to the jury in assessing the evidence and their relative comprehensibility. The different thematic approaches produced disparate choices concerning the evidence -- its selection for consideration and its evaluation. The approach in the first summation resulted in an analysis of the evidence that favoured the accused. In the second summation, the thematic approach facilitated a more critical appraisal of the accused's case and a more favourable assessment of the complainant's version of events. The summations also provide differential levels of assistance and achieve differential levels of comprehensibility. The first summation provides relatively little guidance to the jury in evaluating significant items of evidence. In contrast, the second trial summation gives a more directional appraisal. It also achieves a greater level of clarity in the communication of key ideas than the first summation. Both distinctions are attributed to the discourse structures of the summations and to the second summation's reliance upon such organisational and rhetorical devices as repetition, enumeration and rhetorical questions. They are also attributed in part to the comparative syntactic simplicity of the second summation's sentences. It is the conclusion of this paper that the trial judge's linguistic, discourse construction and rhetorical skills are central to the clarification or obfuscation of the facts and issues in a case. How judges say what they say is significant at two levels of sense construction -- at the level of what Bernard Jackson calls “signification” and at the level of communication.

Electronic Resource

1572-946X

Springer Online Journal Archives 1860-2000

Physics

Electronic Resource

1572-946X

Springer Online Journal Archives 1860-2000

Physics

Abstract In this paper we study the influence of model parameters adopted in radiative transfer computations on the shape of the 10 and 20 μm bands observed in IR spectra of Becklin-Neugebauer objects and O-rich giants and supergiants. The calculations show that besides the wavelength-dependence of the absorption efficiency the optical depth is the most important parameter. From the appearance of the 10 μm feature we can distinguish three different regions: emission, self-absorption and absorption. The most important effect demonstrated by the model computations is that an emission feature shows a weaker variation than an absorption feature if the optical depth is increased or decreased. Furthermore shells with central-peaked density distributions should exhibit stronger emission bands and weaker absorption bands than shells with a constant density.

Electronic Resource

1572-946X

Springer Online Journal Archives 1860-2000

Physics

Abstract In this paper the mean relative efficiency factors for absorption of dust grains in the wavelength range from 8 to 22 μm have been derived from IR spectra of the optically thin dust shells surrounding the O-rich supergiants μ Cep, αOri, X Her, and R Cas. The resulting absorption efficiency curve has been extrapolated into the near as well as the far infrared regions, having regard to restrictions set by experience. Planck mean efficiency factors have been calculated for the temperature range from 30 to 1500 K. The curveQ P(T), which shows a maximum atT=300 K, has been approximated conveniently by a power law on either side of this maximum.

Electronic Resource

1432-0843

Key words: ADR-529 – Cardioprotection – Metastatic breast cancer

Springer Online Journal Archives 1860-2000

Medicine

Abstract. The purpose of this study was to determine the maximal tolerable dose (MTD) of epirubicin and ADR-529 given in combination with cyclophosphamide, 5-fluorouracil, and tamoxifen. A total of 64 breast cancer patients with locally advanced disease or a first metastatic event were included. Using fixed doses of cyclophosphamide, 5-fluorouracil, and tamoxifen, cohorts of ten patients were treated with escalating doses of epirubicin and ADR-529. With the use of protocol criteria specifying evaluation after the first course, the MTD was not reached. Dose reductions carried out due to hematologic toxicity during the first four courses made it impossible to escalate doses of epirubicin beyond 80 mg/m2 given together with ADR-529 600 mg/m2. The vascular toxicity of ADR-529 necessitated central venous access in a number of patients. For phase III evaluation of ADR-529 given together with cyclophosphamide, epirubicin, 5-fluorouracil, and tamoxifen (CEF/TAM) we recommend using epirubicin/ADR-529 at 60/600 mg/m2. Together with evaluation of the cardioprotective properties of ADR-529, we recommend evaluating the impact of ADR-529 on the efficacy of cytotoxic therapy and investigating further the toxicity of ADR-529.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary Pharmacokinetic analysis of epirubicin and its metabolites epirubicinol and 7-deoxy-13-dihydro-epirubicinol aglycone during the first and the fourth courses of treatment was performed in 78 patients with metastatic breast cancer. The patients were treated every 3 weeks with epirubicin given as 10-min i.v. infusions at four different dose levels: 40, 60, 90 and 135 mg/m2. In most cases (76 of 78 cases), plasma concentration-time curves fitted to a three-compartmental pharmacokinetic model. The terminal half-life of epirubicin was independent of dose and duration of treatment. Large interindividual differences were demonstrated (meant 1/2γ, 21.6±7.9 h; range, 10.6–69 h;n=110). In two subjects, extremely long half-lives and high serum bilirubin concentrations indicated impaired liver function. No correlation was found between the half-life and levels of liver alanine aminotransferase (ALAT) or serum creatinine. The metabolite epirubicinol appeared quickly after epirubicin administration and its half-lives were shorter than that of the parent compound (meant 1/2γ, 18.1±4.8 h; range, 8.2–38.4 h;n=105).Formation of the aglycone metabolite was delayed and the half-life of this metabolite was shorter than that of epirubicin (meant 1/2γ, 13±4.6 h; range, 2.7–29 h;n=104). The AUC of epirubicin and the total AUC (drug and metabolites) were linearly proportional to the dose, with the former value constituting two-thirds of the latter. A correlation was found between AUC and the plasma concentration of epirubicin at two time points (2 and 24 h after administration). The proposed model was AUC=9.44×c 2+62.5×c 24+157.7 (r=0.953).

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirubicin. A similar correlation was observed when the metabolite epirubicinol was also considered. The decrease in leucocyte count as expressed by the logarithmic ratio between nadir WBC and initial WBC was linearly correlated with the AUC of either epirubicin alone (r=−0.55,P〈0.001) or epirubicin and epirubicinol together (r=−0.63,P〈0.001). As a relationship between the concentration of epirubicin in a single plasma sample taken at 6 h following i.v. administration and the AUC of the drug has been established, a log-linear relationship between the expected decrease in leucocytes and the concentration at 6 h after administration could be calculated. The proposed model is expressed as the equation: log WBCnadir=log WBCinitial−0.0073×c 6 (ng/ml) −0.14.

Electronic Resource

1432-0843

ADR-529 ; Cardioprotection ; Metastatic breast cancer

Springer Online Journal Archives 1860-2000

Medicine

Abstract The purpose of this study was to determine the maximal tolerble dose (MTD) of epirubicin and ADR-529 given in combination with cyclophophamide, 5-fluorouracil, and tamoxifen. A total of 64 breast cancer patients with locally advanced disease or a first metastatic event were included. Using fixed doses of cyclophosphamide, 5-fluorouracil, and tamoxifen, cohorts of ten patients were treated with escalating doses of epirubicin and ADR-529. With the use of protocol criteria specifying evaluation after the first course, the MTD was not reached. Dose reductions carried out due to hematologic toxicity during the first four courses made it impossible to escalate doses of epirubicin beyond 80 mg/m2 given together with ADR-529 600 mg/m2. The vascular toxicity of ADR-529 necessitated central venous access in a number of patients. For phase III evaluation of ADR-529 given together with cyclophosphamide, epirubicin, 5-fluorouracil, and tamoxifen (CEF/TAM) we recommend using epirubicin/ADR-529 at 60/600 mg/m2. Together with evaluation of the cardioprotective properties of ADR-529, we recommend evaluating the impact of ADR-529 on the efficacy of cytotoxic therapy and investigating further the toxicity of ADR-529.

Electronic Resource

1432-0843

Key words Pharmacokinetics ; ADR-529 ; Epirubicin ; Metastatic breast cancer ; High-pressure liquid chromatography

Springer Online Journal Archives 1860-2000

Medicine

Abstract  A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-μm silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i. v. administration of different doses of ADR-529 (600 – 1000 mg/m2) together with different doses of epirubicin (E, 60 – 100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.

Electronic Resource

1432-0843

Pharmacokinetics ; ADR-529 ; Epirubicin ; Metastatic breast cancer ; High-pressure liquid chromatography

Springer Online Journal Archives 1860-2000

Medicine

Abstract A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-μm silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m2) together with different doses of epirubicin (E, 60–100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.

Electronic Resource

1432-0754

Springer Online Journal Archives 1860-2000

Physics

Summary Cosmic dust grains play an important role for the thermal, dynamical, and chemical structure of the interstellar medium. This is especially true for the star formation process and the late stages of stellar evolution. Dust grains determine the spectral appearance of protostars, very young stellar objects with disk-like structures as well as of evolved stars with circumstellar envelopes. In this review, we will demonstrate that solid particles in interstellar space are both agent and subject of galactic evolution. We will especially discuss the different dust populations in circumstellar envelopes, the diffuse interstellar medium, and the molecular clouds with strong emphasis on the evolutionary aspects and the metamorphosis of these populations.

Electronic Resource

1432-2323

Springer Online Journal Archives 1860-2000

Medicine

Résumé Le rôle du traitement anti-oestrogénique du cancer du sein opéré après la ménopause chez les malades à hauts risques de récidive a été soumis à une étude prospective randomisée sur le plan national par le groupe Danois d'Etude du Cancer du Sein. Cette étude comporte d'une part 829 malades qui après mastectomie totale et radiothérapie postopératoire ont été traitées par le tamoxifen (RT + TAM) pendant un an et d'autre part 821 malades qui n'ont pas été soumises à un traitement complémentaire (RT). L'absence de récidive après 3 ans a été de 44% dans le premier groupe et de 40% dans le second. Dans les deux groupes le taux de la survie à 5 ans a été de 51% (p=0.53). Le pronostic basé sur les données rassemblées a été étudié en fonction de plusieurs facteurs: âge, degré d'anaplasie, volume de la tumeur, envahissement ganglionnaire. Le taux d'absence de récidive à 3 ans a été plus bas chez les malades traitées par l'association radiothérapie et tamoxifen mais il n'a de valeur significative que chez les malades âgées de 50 à 59 ans, présentant des tumeurs dont l'anaplasie est de stade I, le volume est inférieur à 5 cm et l'envahissement concerne 4 ganglions ou plus. La concentration oestrogénique a été dosée chez 291 de ces malades. La limite de 10 fmol/mg cytosol protéine et l'emploi du modèle des risques proportionnels Cox ont permis la distinction entre malades à hauts risques de récidive à 3 ans et les autres. Les malades dont le pouvoir récepteur oestrogénique est inférieur à 100 fmol/mg ne tirent aucun bénéfice du traitement endocrinien contrairement à ceux dont le pouvoir est supérieur. Le pouvoir récepteur progestéronique a été étudié chez 12% des malades. Celles qui ont un pouvoir positif ont un taux de récidive moins élevé quand elles sont traitées par RT + TAM par rapport à celles qui sont traitées seulement par RT (p=0.017).

Resumen La evaluación del valor del tratamiento antiestrógeno en pacientes postmenopáusicas con cáncer de seno con alto riesgo de enfermedad recurrente fue realizada en un ensayo nacional prospectivo y aleatorizado conducido por el Grupo Danés de Cáncer de Seno. Después de haber sido sometidas a mastectomía total y radioterapia postoperatoria, 829 pacientes fueron asignadas en forma aleatoria a tratamiento con Tamoxifén (RT + TAM) por 1 año, y 821 no recibieron tratamiento adicional (RT). La sobrevida libre de recurrencia (SLR) a los 72 meses es de 44% en el grupo RT + TAM, y de 40% en el grupo RT (p=0.003). La supervivencia global es de 51% en ambos grupos (p =0.53). Los datos han sido analizados con respecto a factores de pronóstico, incluyendo edad, grado de anaplasia, tamańo del tumor y ganglios positivos. La SLR es mayor en los subgrupos de pacientes tratadas con RT + TAM, pero es de significación sólo en los grupos de edad entre 50 y 59 años con tumores de anaplasia grado I, de tamaño menor de 5 cm y con 4 o más ganglios linfáticos positivos. Aún cuando se presentaron menos metastasis locales y distantes en las pacientes tratadas con RT + TAM, no se logró un aumento en la supervivencia global y aún en aquellos subgrupos de pacientes con las más significativas prolongaciones de la SLR no se pudo demostrar aumento de la supervivencia. La concentración de receptores de estrógeno fue medida en un subgrupo de 291 de las pacientes. Un límite bajo de 10 fmol/mg de proteína citosólica, distingue a las pacientes con prolongada SLR de aquellas con enfermedad recurrente temprana. Las pacientes con contenidos de receptores de estrógenos por debajo de 100 fmol/mg no derivaron beneficio de la terapia endocrina mientras aquellas con concentraciones superiores a 100 fmol/mg exhibieron una SLR significativamente más prolongada. Determinaciones de receptores de progesterona fueron realizadas en el 12% de las pacientes. Las pacientes con receptores de progesterona positivos tuvieron una menor tasa de recurrencia con el regimen RT + TAM que las pacientes con receptores de progesterona positivos manejadas con RT solamente (p=0.017). En conclusión, la terapia adyuvante con TAM aumenta la SLR en pacientes postmenopáusicas con cáncer mamario de alto riesgo. La eficacia está significativamente correlacionada con la edad de las pacientes y con ciertas características histopatológicas y bioquímicas de los tumores. El valor pronóstico de las determinaciones de RE se logra al emplear un límite bajo en la positividad RE el cual esencialmente sirve para distinguir los tumores RE negativos de los RE positivos. El valor de predicción de las determinaciones de RE y de RPg en cuanto al efecto de la terapia adyuvante parece depender sólo de las concentraciones de RE y RPg en el tejido tumoral, puesto que las más bajas tasas de recurrencia se presentan en pacientes con las más altas concentraciones.

Abstract The role of anti-estrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective, randomized trial conducted by the Danish Breast Cancer Group. After total mastectomy and postoperative radiotherapy, 829 patients were randomized to treatment with tamoxifen (RT + TAM) for 1 year and 821 were randomized to no further therapy (RT). The recurrence-free survival (RFS) after 72 months of life-table analysis is 44% in the RT + TAM treated group, and 40% in the RT group (p=0.0003). Survival is 51% in both treatment groups (p=0.53). The data have been further analyzed with respect to prognostic factors such as age, degree of anaplasia, tumor size, and positive nodes. The RFS is lower in all subsets of patients treated with RT + TAM, but is only significant in patients 50–59 years of age, with tumors of anaplasia grade I, with tumors less than 5 cm, or with 4 or more positive lymph nodes. Estrogen receptor concentrations were measured in a subset of 291 of these patients. A cut-off limit of 10 fmol/mg cytosol protein and the use of a Cox proportional hazards model distinguished between patients with long RFS and those with early recurrent disease. Patients with an estrogen receptor content below 100 fmol/mg did not benefit from the endocrine therapy, while those with concentrations above 100 fmol/mg had a significantly longer RFS. Progesterone receptor determinations were performed in 12% of the patients. Progesterone receptor-positive patients had a lower rate of recurrence when treated with RT + TAM compared to the receptor-positive patients in the RT group (p=0.017).

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