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The aim of this observational study was to follow-up patients with bedtime basal insulin (NPH insulin) added to metformin. In 285 patients with type 2 diabetes, a therapy with bedtime basal insulin added to metformin was started due to failure to achieve a glycaemic goal. Up until July 2019, 272 patients (95.4%) were followed-up (59.5 y, 92.6 kg, diabetes duration 6.6 y, HbA1c 8.4%/68.6 mmol/mol). HbA1c decreased by −1.2% and bodyweight by −1.7 kg after a duration of 31.7 ± 29.1 (range 2–133) months. Severe hypoglycaemia did not occur. In 144/272 patients (52.9%), the therapeutic goal for HbA1c was achieved over 32.7 months. In 69/272 patients (25.4%), the HbA1c target was achieved over 25.0 months (afterwards, therapy with basal insulin was discontinued because HbA1c was under target). In 36/272 patients (13.2%), the HbA1c goal was achieved until the submission of this manuscript (mean duration of treatment 57.4 ± 28.2 (range 13–121) months). Over 90% of patients with type 2 diabetes and failure of metformin reached their HbA1c goal with additional basal insulin at bedtime over several years in association with a reduction of bodyweight and without any event of severe hypoglycaemia.
A novel method for the highly stereoselective synthesis of tetrahydropyrans is reported. This domino reaction is based on a twofold addition of enamides to aldehydes followed by a subsequent cyclization and furnishes fully substituted tetrahydropyrans in high yields. Three new σ‐bonds and five continuous stereogenic centers are formed in this one‐pot process with a remarkable degree of diastereoselectivity. In most cases, the formation of only one out of 16 possible diastereomers is observed. Two different stereoisomers can be accessed in a controlled fashion starting either from an E‐ or a Z‐configured enamide.
Die Landschaftsstation im Kreis Höxter wird zumeist über ihre Beteiligung an verschiedenen, im Fokus der Öffentlichkeit stehenden Projekten wahrgenommen. Dazu zählt das Projekt „Erlesene Natur“, in dessen Rahmen viel beachtete Erlebnisgebiete wie der Weser-Skywalk im NSG „Hannoversche Klippen“, der neu gestaltete Wanderweg im NSG „Desenberg“ oder das Weidenpalais, ein gewaltiges Lebendbauwerk im Schlosspark Rheder, entstanden. Dazu zählen auch die naturnahe Gestaltung mittelwaldähnlicher Waldränder, Forschungsarbeiten zum Klimawandel sowie das 2011 begonnene Naturschutzprojekt „Vielfalt auf Kalk“ zur Optimierung von insgesamt 11 Trockenlebensräumen im Kreis Höxter. Gerne nutzen wir die „Beiträge zur Naturkunde zwischen Egge und Weser“, um Sie, liebe Leserinnen und Leser, über die Ziele und den Fortgang unserer Projekte zu informieren. Der nachfolgende Tätigkeitsbericht bezieht sich auf die originären Aufgaben unserer Station, die von der Bevölkerung zwar nicht so intensiv wahrgenommen werden wie die oben beschriebenen Projekte, denen wir aber den Großteil unserer Arbeitszeit widmen. Bevor wir die fachlichen Aspekte unserer Arbeit darlegen, möchten wir die Einführung nutzen, um Sie über aktuelle Entwicklungen in unserer Geschäftsstelle zu informieren. Über 10 Jahre lang haben Zivildienstleistende die praktische Landschaftspflege in der Station entscheidend mit geprägt. Am 31. August 2011 endete diese Ära mit dem letzten Arbeitstag von Jannis IFFLAND, dem letzten „Zivi“ der Landschaftsstation. Ihm und all seinen Vorgängern gilt unser Dank für Ihren engagierten Einsatz zum Wohle der Natur im Kreis Höxter. Das bisherige Niveau der Landschaftspflegearbeiten wurde auch im Jahr 2011 durch die Stammbesetzung im Pflegetrupp mit Vorarbeiter Ralf SCHAPERDOT und Mitarbeiter Lars MASSMANN abgesichert. Die notwendigen personellen Verstärkungen zur Umsetzung der vielfältigen Aufgaben erfolgten einen Monat nach dem Weggang des letzten Zivis. Im Oktober 2011 leitete Pablo MENN aus Warburg als erster Bundesfreiwilliger der Landschaftsstation eine neue Ära ein. Der Bundesfreiwilligendienst (BFD) wird als Nachfolgemodell zum bisherigen Zivildienst über den Bund finanziert. Die Einsatzzeit beträgt in der Regel 12 Monate. Im Vergleich zum Zivildienst besitzt der BFD einen deutlich höheren Bildungscharakter, der allein schon durch die vorgeschriebene Mindestzahl von 25 Bildungstagen/ Jahr für Teilnehmer/innen unter 27 Jahren deutlich wird. Die Landschaftsstation möchte Bundesfreiwilligen einen interessanten Mix aus dem breiten Aufgabenspektrum des Naturschutzes anbieten, der sich nicht nur auf die Landschaftspflege beschränkt, und freut sich auf weitere Bewerberinnen und Bewerber. Als weitere Verstärkung wurde ebenfalls im Oktober Werner HEINEMEIER aus Höxter eingestellt. Er wird als Teilnehmer des bundesweiten Modellprojektes „Bürgerarbeit“ über die ARGE Höxter kofinanziert und hat sich bemerkenswert schnell in die Arbeitsabläufe der Station integriert. Personelle Änderungen ergaben sich im Projektteam „Erlesene Natur“ durch das freiwillige Ausscheiden von Birte BRAND, die mit großem Engagement jeweils eine halbe Stelle beim Kreis Höxter und bei der Landschaftsstation ausfüllte. Sie betreibt inzwischen in ihrem Heimatdorf Hagedorn die „Futterkrippe“, einen kleinen Regionalladen. Die freigewordene halbe Stelle in der Station konnte im Anschluss mit Eike SPELLERBERG aus Höxter neu besetzt werden. Ihre Aufgabenschwerpunkte liegen im Bereich der Umsetzung von Maßnahmen und umfassen neben den Ausschreibungen auch die Bauüberwachung und die Abnahme der Gewerke. Weitere Verstärkung erhielt die Geschäftsstelle durch die Einstellung von Michael TILLY, der bereits über Praktika und Werkverträge für die Landschaftsstation tätig war und sich als „Allrounder“ in der Landschaftspflege sowie der Bearbeitung wissenschaftlicher Aufgabenstellungen bewährt hatte. Wie in den vergangenen Jahren waren auch 2011 wieder eine Reihe von Praktikantinnen und Praktikanten an der erfolgreichen Bearbeitung diverser Aufgaben in der Station beteiligt. So kümmerte sich Benjamin GERECKE im Rahmen eines über die ARGE finanzierten Praktikums und einer darauf folgenden halbjährigen Festeinstellung erfolgreich um den Aufbau einer GIS-gestützten Access-Datenbank und die Entwicklung einer praktikablen Eingabemaske. Britta LIEBE aus Höxter unterstützte im Rahmen ihres fünfmonatigen Praxissemesters insbesondere eine Vielzahl von Artenschutzmaßnahmen. Ihnen und allen an dieser Stelle namentlich nicht aufgeführten Helfern und ehrenamtlichen Unterstützern gebührt unser Dank. Sie alle haben dazu beigetragen, dass unser Verein den Naturschutz im Kreis Höxter weiter etablieren konnte. Unser Dank gilt weiterhin den Fachbehörden und Naturschutzverbänden/- vereinen für die gute Zusammenarbeit. Unser Dank gilt auch dem Ministerium für Klimaschutz, Umwelt, Landwirtschaft, Natur- und Verbraucherschutz (MKULNV) für die hohe Wertschätzung der Arbeit der Biologischen Stationen in NRW. Nach vielen aus finanzieller Sicht schwierigen Jahren wurde 2011 der Gesamtetat zur Finanzierung der Biologischen Stationen in NRW angehoben und bis 2015 gesichert. Ein Erfolg für den Naturschutz in NRW, maßgeblich beeinflusst vom rührigen Vorstand des Dachverbandes der Biologischen Stationen. Das nachfolgend dokumentierte, vielfältige Aufgabenspektrum der Station führt dazu, dass die hauptamtlichen Mitarbeiter Umweltbildung in Form von Exkursionen und Vorträgen nicht in der eigentlich gewünschten Quantität anbieten können. Diese vermeintliche Lücke wird inzwischen hervorragend von den auch über die Landschaftsstation ausgebildeten „KulturLand- Führern“ geschlossen, deren Angebote jeweils in einem ansprechenden Jahresprogramm zusammengefasst werden (s. www.kulturland.org). Dennoch können Sie Exkursionswünsche weiterhin gerne an unsere Geschäftsstelle richten. Bei Interesse nehmen wir vorzugsweise im Winterhalbjahr auch gerne Einladungen zu Versammlungen wahr, um unsere Lebensräume und Naturschätze im Kreis Höxter, sowie die Arbeit der Landschaftsstation zu präsentieren.
Background and purpose: Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction.
Methods: The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD-EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m2. eGFR dynamics were classified based on two in-hospital values as “stable normal” (≥60 ml/min/1.73 m2), “increasing” (by at least 15% from baseline, second value ≥ 60 ml/min/1.73 m2), “decreasing” (by at least 15% from baseline of ≥60 ml/min/1.73 m2), and “stable decreased” (<60 ml/min/1.73 m2). The composite endpoint (stroke, major bleeding, myocardial infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder-adjusted models.
Results: Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m2 at baseline (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.40–3.54) as well as decreasing (HR = 1.79, 95% CI = 1.07–2.99) and stable decreased eGFR (HR = 1.64, 95% CI = 1.20–2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95% CI = 1.51–6.10) and decreasing eGFR were associated with all-cause death (HR = 3.12, 95% CI = 1.63–5.98).
Conclusions: In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction.
Purpose: Preoperative (neoadjuvant) chemoradiotherapy (CRT) and total mesorectal excision is the standard treatment for rectal cancer patients (UICC stage II/III). Up to one-third of patients treated with CRT achieve a pathological complete response (pCR). These patients could be spared from surgery and its associated morbidity and mortality, and assigned to a “watch and wait” strategy. However, reliably identifying pCR based on clinical or imaging parameters remains challenging.
Experimental design: We generated gene-expression profiles of 175 patients with locally advanced rectal cancer enrolled in the CAO/ARO/AIO-94 and -04 trials. One hundred and sixty-one samples were used for building, training and validating a predictor of pCR using a machine learning algorithm. The performance of the classifier was validated in three independent cohorts, comprising 76 patients from (i) the CAO/ARO/AIO-94 and -04 trials (n = 14), (ii) a publicly available dataset (n = 38) and (iii) in 24 prospectively collected samples from the TransValid A trial.
Results: A 21-transcript signature yielded the best classification of pCR in 161 patients (Sensitivity: 0.31; AUC: 0.81), when not allowing misclassification of non-complete-responders (False-positive rate = 0). The classifier remained robust when applied to three independent datasets (n = 76).
Conclusion: The classifier can identify >1/3 of rectal cancer patients with a pCR while never classifying patients with an incomplete response as having pCR. Importantly, we could validate this finding in three independent datasets, including a prospectively collected cohort. Therefore, this classifier could help select rectal cancer patients for a “watch and wait” strategy.
Translational relevance: Forgoing surgery with its associated side effects could be an option for rectal cancer patients if the prediction of a pathological complete response (pCR) after preoperative chemoradiotherapy would be possible. Based on gene-expression profiles of 161 patients a classifier was developed and validated in three independent datasets (n = 76), identifying over 1/3 of patients with pCR, while never misclassifying a non-complete-responder. Therefore, the classifier can identify patients suited for “watch and wait”.
In situ measurements of ice crystal size distributions in tropical upper troposphere/lower stratosphere (UT/LS) clouds were performed during the SCOUT-AMMA campaign over West Africa in August 2006. The cloud properties were measured with a Forward Scattering Spectrometer Probe (FSSP-100) and a Cloud Imaging Probe (CIP) operated aboard the Russian high altitude research aircraft M-55 Geophysica with the mission base in Ouagadougou, Burkina Faso. A total of 117 ice particle size distributions were obtained from the measurements in the vicinity of Mesoscale Convective Systems (MCS). Two to four modal lognormal size distributions were fitted to the average size distributions for different potential temperature bins. The measurements showed proportionately more large ice particles compared to former measurements above maritime regions. With the help of trace gas measurements of NO, NOy, CO2, CO, and O3 and satellite images, clouds in young and aged MCS outflow were identified. These events were observed at altitudes of 11.0 km to 14.2 km corresponding to potential temperature levels of 346 K to 356 K. In a young outflow from a developing MCS ice crystal number concentrations of up to (8.3 ± 1.6) cm−3 and rimed ice particles with maximum dimensions exceeding 1.5 mm were found. A maximum ice water content of 0.05 g m−3 was observed and an effective radius of about 90 μm. In contrast the aged outflow events were more diluted and showed a maximum number concentration of 0.03 cm−3, an ice water content of 2.3 × 10−4 g m−3, an effective radius of about 18 μm, while the largest particles had a maximum dimension of 61 μm.
Close to the tropopause subvisual cirrus were encountered four times at altitudes of 15 km to 16.4 km. The mean ice particle number concentration of these encounters was 0.01 cm−3 with maximum particle sizes of 130 μm, and the mean ice water content was about 1.4 × 10−4 g m−3. All known in situ measurements of subvisual tropopause cirrus are compared and an exponential fit on the size distributions is established for modelling purposes.
A comparison of aerosol to ice crystal number concentrations, in order to obtain an estimate on how many ice particles may result from activation of the present aerosol, yielded low ratios for the subvisual cirrus cases of roughly one cloud particle per 30 000 aerosol particles, while for the MCS outflow cases this resulted in a high ratio of one cloud particle per 300 aerosol particles.
In-situ measurements of ice crystal size distributions in tropical upper troposphere/lower stratosphere (UT/LS) clouds were performed during the SCOUT-AMMA campaign over West Africa in August 2006. The cloud properties were measured with a Forward Scattering Spectrometer Probe (FSSP-100) and a Cloud Imaging Probe (CIP) operated aboard the Russian high altitude research aircraft M-55 ''Geophysica'' with the mission base in Ouagadougou, Burkina Faso. A total of 117 ice particle size distributions were obtained from the measurements in the vicinity of Mesoscale Convective Systems (MCS). Two or three modal lognormal size distributions were fitted to the average size distributions for different potential temperature bins. The measurements showed proportionate more large ice particles compared to former measurements above maritime regions. With the help of trace gas measurements of NO, NOy, CO2, CO, and O3, and satellite images clouds in young and aged MCS outflow were identified. These events were observed at altitudes of 11.0 km to 14.2 km corresponding to potential temperature levels of 346 K to 356 K. In a young outflow (developing MCS) ice crystal number concentrations of up to 8.3 cm−3 and rimed ice particles with maximum dimensions exceeding 1.5 mm were found. A maximum ice water content of 0.05 g m−3 was observed and an effective radius of about 90 μm. In contrast the aged outflow events were more diluted and showed a maximum number concentration of 0.03 cm−3, an ice water content of 2.3 × 10−4 g m−3, an effective radius of about 18 μm, while the largest particles had a maximum dimension of 61 μm.
Close to the tropopause subvisual cirrus were encountered four times at altitudes of 15 km to 16.4 km. The mean ice particle number concentration of these encounters was 0.01 cm−3 with maximum particle sizes of 130 μm, and the mean ice water content was about 1.4 × 10−4 g m−3. All known in-situ measurements of subvisual tropopause cirrus are compared and an exponential fit on the size distributions is established in order to give a parameterisation for modelling.
A comparison of aerosol to ice crystal number concentrations, in order to obtain an estimate on how many ice particles result from activation of the present aerosol, yielded low activation ratios for the subvisual cirrus cases of roughly one cloud particle per 30 000 aerosol particles, while for the MCS outflow cases this resulted in a high ratio of one cloud particle per 300 aerosol particles.
We present the black hole accretion code (BHAC), a new multidimensional general-relativistic magnetohydrodynamics module for the MPI-AMRVAC framework. BHAC has been designed to solve the equations of ideal general-relativistic magnetohydrodynamics in arbitrary spacetimes and exploits adaptive mesh refinement techniques with an efficient block-based approach. Several spacetimes have already been implemented and tested. We demonstrate the validity of BHAC by means of various one-, two-, and three-dimensional test problems, as well as through a close comparison with the HARM3D code in the case of a torus accreting onto a black hole. The convergence of a turbulent accretion scenario is investigated with several diagnostics and we find accretion rates and horizon-penetrating fluxes to be convergent to within a few percent when the problem is run in three dimensions. Our analysis also involves the study of the corresponding thermal synchrotron emission, which is performed by means of a new general-relativistic radiative transfer code, BHOSS. The resulting synthetic intensity maps of accretion onto black holes are found to be convergent with increasing resolution and are anticipated to play a crucial role in the interpretation of horizon-scale images resulting from upcoming radio observations of the source at the Galactic Center.
A highly diastereoselective one-pot synthesis of the 1,3-diamino-2-alcohol unit bearing three continuous stereocenters is described. This method utilizes 2-oxyenamides as a novel type of building block for the rapid assembly of the 1,3-diamine scaffold containing an additional stereogenic oxygen functionality at the C2 position. A stereoselective preparation of the required (Z)-oxyenamides is reported as well.
Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au + Au collisions at √sNN = 130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are K+/π− = 0.161± 0.002(stat) ± 0.024(syst) and K−/π− = 0.146± 0.002(stat) ± 0.022(syst) for the most central collisions. The K+/π− ratio is lower than the same ratio observed at the SPS while the K−/π− is higher than the SPS result. The ratios are enhanced by about 50% relative to p + p and p¯ + p collision data at similar energies.