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  • 1
    Abstract: Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab.
    Type of Publication: Journal article published
    PubMed ID: 28124380
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  • 2
    Keywords: FOLLOW-UP ; COHORT ; IMPACT ; DIABETES-MELLITUS ; STROKE ; CARDIOVASCULAR-DISEASE ; CORONARY-HEART-DISEASE ; FASTING GLUCOSE ; PRIOR MYOCARDIAL-INFARCTION ; MILLION PEOPLE
    Abstract: IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
    Type of Publication: Journal article published
    PubMed ID: 26151266
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    HNO 44 (1996), S. 553-554 
    ISSN: 1433-0458
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Skeletal radiology 20 (1991), S. 222-225 
    ISSN: 1432-2161
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0630
    Keywords: 61.70 ; 66.30
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Aluminum diffusion profiles in silicon were produced under rapid thermal processing conditions using a Si-sandwich structure to avoid losses of aluminum by reaction with the quartz reactor. The impact of phosphorus on the diffusion behaviour of aluminum was investigated by predeposition of P into Al-diffused wafers and vice versa. Dopant profiles were determined by SIMS (Secondary-Ion-Mass Spectroscopy), electrochemical CV-and SRP (Spreading Resistance) analysis. The resulting profiles after Al predeposition at 1293 K exhibit high Al-surface concentrations up to the solid solubility limit of about 2×1025 m−3. It is shown that phosphorus has a great influence on the drivein behaviour of Al, leading to an accelerated Al diffusion in front of the P profile (enhanced Al diffusion caused by self-interstitial supersaturation) and an “up-hill migration” of Al in the high-concentration regime, which can be explained by field-assisted diffusion. A strong retardation of aluminum diffusion combined with concentrations well above the solidsolubility limit was observed during the Al predeposition into P-diffused wafers.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Two composting systems were compared on a laboratory scale as a bioredediation technology for degradation or immobilization of 2,4,6-trinitrotoluene (TNT) in contaminated soils. The first compost was aerated from the beginning whereas the second compost was only aerated after an anaerobic prephase of 65 days. In the first compost system the TNT concentration declined rapidly by 92% but, at the end, TNT could be partially recovered. During the anaerobic prephase of the second compost system, TNT was almost completely converted to aminodinitrotoluenes, which during the subsequent aeration almost entirely disappeared. In addition, the second compost generated less toxic material than the first one as confirmed by inhibition of bioluminescence ofVibrio fischeri. These data show that microbiological TNT-degradation systems can be successfully designed which are prerequisite for an efficient bioremediation of contaminated soils.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0614
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Two composting systems were compared on a laboratory scale as a bioremediation technology for degradation or immobilization of 2,4,6-trinitrotoluene (TNT) in contaminated soils. The first compost was aerated from the beginning whereas the second compost was only aerated after an anaerobic prephase of 65 days. In the first compost system the TNT concentration declined rapidly by 92% but, at the end, TNT could be partially recovered. During the anaerobic prephase of the second compost system, TNT was almost completely converted to aminodinitrotoluenes, which during the subsequent aeration almost entirely disappeared. In addition, the second compost generated less toxic material than the first one as confirmed by inhibition of bioluminescence of Vibrio fischeri. These data show that microbiological TNT-degradation systems can be successfully designed which are prerequisite for an efficient bioremediation of contaminated soils.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0630
    Keywords: PACS: 61.70; 66.30
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract. Aluminum diffusion profiles in silicon were produced under rapid thermal processing conditions using a Si-sandwich structure to avoid losses of aluminum by reaction with the quartz reactor. The impact of phosphorus on the diffusion behaviour of aluminum was investigated by predeposition of P into Al-diffused wafers and vice versa. Dopant profiles were determined by SIMS (Secondary-Ion-Mass Spectroscopy), electrochemical CV- and SRP (Spreading Resistance) analysis. The resulting profiles after Al predeposition at 1293 K exhibit high Al-surface concentrations up to the solid solubility limit of about 2×1025 m−3. It is shown that phosphorus has a great influence on the drive-in behaviour of Al, leading to an accelerated Al diffusion in front of the P profile (enhanced Al diffusion caused by self-interstitial supersaturation) and an "up-hill migration" of Al in the high-concentration regime, which can be explained by field-assisted diffusion. A strong retardation of aluminum diffusion combined with concentrations well above the solid-solubility limit was observed during the Al predeposition into P-diffused wafers.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1434-4726
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An 9 narkotisierten und curaresierten Meerschweinchen wurde das Summenaktionspotential des linken Hörnerven mit einer großen Drahtelektrode abgeleitet. Das Potential wurde durch elektrischen punktförmigen Reiz an der linken Lamina spiralis erzeugt. Die experimentellen Bedingungen ließen sich über mehrere Stunden konstant halten. Das Summenaktionspotential des Hörnerven hat 3 negative Gipfel, genannt N1, N2 und N3. Dabei tritt N1 bei den geringsten elektrischen Reizstärken auf, bei etwas größeren Stärken erscheint N2, und bei noch größeren Reizstärken schließlich N3. Die Größe von N1, N2 und N3 ist eine im ganzen kontinuierliche, S-förmige Funktion der elektrischen Reizstärke, solange die Reizdauer konstant gehalten bleibt. Die Latenzen von N1, N2 und N3 werden mit zunehmender elektrischer Reizstärke kürzer. Die Laufzeit durch die Schnecke ist für N1, N2 und N3 fast identisch, sie differiert nur um 0,1 msec. Dieser Befund stützt die alte Annahme, daß die Verschlüsselung der Lautstärke zum Teil schon auf der Höhe der primären, auditorischen Neurone durchgeführt wird.
    Notes: Summary Nine guinea pigs, anaesthetized and fully curarized, were used in the present experiments. A compound action pptential of the left cochlear nerve was evoked by electrical stimulation of a small section of the homolateral spiral lamina. This compound action potential was recorded for many hours. 1. The auditory nerve when stimulated electrically generates three peaks (N1, N2, N3). The appearance of N2 and N3 depends on the stimulating energy, N1 having the lowest threshold, N2 a higher and N3 the highest threshold. 2. The intensity function of the N1− or N2−- or N3 amplitude is a continuous but non-linear function with only one point of Inflexion. 3. Latencies get shorter as the stimulating energy increases. 4. The time needed for the three peaks to run through the cochlea differs by 0.1 msec. A peripheral coding of loudness generated by the auditory nerve fibres seems to exist.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 37 (1981), S. 773-775 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A solution of 0.0625% 1,2-di-n-butylhydrazine dihydrochloride (1,2-DBH) was given continuously in the drinking water of 6-week-old randomly bred albino Swiss mice for the remainder of their lives. The treatment gave rise to tumors of the lungs, lymphoreticular tissue and kidneys.
    Type of Medium: Electronic Resource
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