Limits and possibilities in evaluating groundwater lake water interactions by stable isotopes

Eidesstattliche Erklärung Vorwort und Dankeschön Zusammenfassung 1 Ausgangsfragen und Zielsetzungen des Projekts 2 Durchgeführte Feld- und Laborarbeiten 3 Ergebnisse und Interpretation 4 Grenzen des Isotopenbilanzmodells 5 Literatur A. Seebach, S. Dietz, D. Lessmann and K. Knöller. 2008. Estimation of lake water - groundwater interactions in meromictic mining lakes by modelling isotope signatures of lake water. Isotopes in Environmental and Health Studies, 44(1): 99-110. A. Seebach, C. von Rohden, J. Ilmberger, S.M. Weise and K. Knöller. 2010. Dating problems with selected mining lakes and the adjacent groundwater body in Lusatia, Germany. Isotopes in Environmental and Health Studies (in print). A. Seebach and K. Knöller. 2010. Water Balance Studies in Remote Areas – Limits and Possibilities in Evaluating Groundwater-Lake Water Interactions by Stable Isotopes. Journal of Hydrology (submitted). Lebenslauf LiteraturlisteAn drei Untersuchungsstandorten in der Niederlausitz wurde versucht, der monatliche Grundwassereintrag isotopenhydrologisch (Sauerstoff-18, Deuterium) zu berechnen. Die Untersuchungen wurden an zwei meromiktischen sowie einem polymiktischen Tagebausee durchgeführt. Ziel der Untersuchungen war es, die für durchmischte Seen etablierte isotopenhydrologische Bilanzgleichung zu abzuwandeln und damit die Bilanzierung geschichteter Seen zu ermöglichen. Ein weiterer Aspekt waren Studien zur Modifizierung des Craig & Gordon Modells von 1965 (Craig und Gordon, 1965) und dessen Anpassung an Gebiete hoher Luftfeuchtigkeit. Hierzu wurden über einen Untersuchungszeitraum von 2,5 Jahren zeitlich und räumlich hochaufgelöste Proben aus Grundwasser, Seewasser, Verdunstungs-pfannen, Niederschlag und Luftfeuchte genommen und isotopisch (δ18O, D) untersucht. Ferner wurden die meteorologischen Parameter Luftfeuchte und Lufttemperatur sowie die Oberflächenwassertemperatur der untersuchten Seen aufgezeichnet. Diese Daten wurden in einem Bilanzmodell zusammengeführt. Unglücklicherweise traten während des Untersuchungszeitraumes aufgrund der unbekannten hydrogeologischen Situation unvorhersehbare Schwierigkeiten mit der Bestimmung eines lokalen Backgroundwertes für die Isotopensignaturen des Grundwassers auf. Außerdem stellten die hydrodynamischen Rahmenbedingungen an allen drei Standorten die Bilanzierung vor eine Herausforderung. So schränken starke Seespiegelschwankungen durch den begleitenden Wechsel von effluenten und influenten Strömungsbedingungen die Anwendung der Isotopenbilanz enorm ein. Des Weiteren verliefen die Verdunstungsexperimente unter den lokalen meteorologischen Bedingungen nicht zufrieden stellend, was leider erst gegen ende des Untersuchungszeitraums erkannt wurde. Die Ergebnisse dieser Studie zeigen, dass die Anwendbarkeit des Isotopenbilanzmodells bezüglich der Quantifizierung von Grundwassereintragsraten durch die lokalen hydrogeologischen Verhältnisse stark limitiert werden kann. Dennoch konnte durch die umfassenden Gelände- und Laborarbeiten neben einem nahezu lückenlosen Datensatz für die drei Untersuchungsgebiete wertvolle Erkenntnisse zur Weiterführung dieses Projektes sowie zur Umsetzung bei zukünftigen ähnlichen Untersuchungen gewonnen werden. Hierzu zählen u.a. die Entwicklung einer Methode zur direkten isotopischen Bestimmung von Wasserdampf bzw. Evaporat. Ferner konnten für die untersuchten Standorte hochaufgelöste Local Meteoric Water Lines (LMWL) und Evaporation Lines (EL) generiert werden. Darüber hinaus konnten Erkenntnisse über die heterogenen Verteilungsmuster von Isotopensignaturen im Grund- und Seewasser gewonnen werden.The application of stable isotopes is a common tool for evaluating water balances of lakes. In this paper, we present a two-year isotope data set from three study sites in Lusatia, Eastern Germany, where pit lakes have been explored: Mine lake 107 (ML107), lake Waldsee and lake Moritzteich. ML107 is part of a pit lake area in the Lusatian Lignite District near Plessa. The latter two lakes are located in the Muskau Arch Fold, which is an ice-thrust ridge of a moraine formed by the Elsterian glaciation. Aim of the investigations was to quantify monthly groundwater recharge into pit lakes. Two of the three investigated lakes are meromictic, which makes it essential to adapt existing water balance models to permanently stratified lakes. For isotope analyses, high-resolution data sets of lake water, precipitation, and groundwater were collected in addition to comprehensive meteorological records of the three study sites. Evaporation pan experiments as well as the design of a special procedure for collecting monthly average samples of lake evaporate complete the survey of the isotope water balance concerning parameters. Unfortunately, unexpected problems arose during processing the work programme. Namely, the isotope signatures of the local groundwater bodies are not uniform in none of the investigated sites. Moreover, seasonal lake water level fluctuations accompany regular changes in the hydrodynamic system; surface water infiltration into the groundwater aquifer alternates with groundwater exfiltration into the lake water body. The results of this study show that the hydro-/geological setting at the study sites in the Muskau Arch Fold is far too complex for the application of well-established water balance models in terms of quantification of groundwater recharge. Furthermore, evaporation pan experiments carried out in the framework of these investigations do not bring any satisfactory results under local meteorological conditions. Regardless of problems mentioned above, the present work introduces a nearly complete high- resolution isotope data set from three mine lakes in the Lusatian Lignite District. So the first local meteoric water and evaporation line were generated for the study areas. The novel technique for sampling lake evaporate allowed obtaining more than thirty water samples which provided (discontinuous) records of isotope signatures of lake evaporate δE. For all evaluated components of the hydrological balance (precipitation, groundwater, lake water, lake evaporate) seasonal pattern were observed. Such as, the amplitude height of the temporal variations in surface lake water isotope composition was between 2.43 ‰ (Moritzteich) and 4.43 ‰ (ML107) for oxygen-18, respectively

High Response Rate With Extended Dosing of Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma

BACKGROUND: Cemiplimab (Libtayo METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review. RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

Interim Analysis of Phase 2 Results for Cemiplimab in Patients with Metastatic Basal Cell Carcinoma (mBCC) who Progressed on or are Intolerant to Hedgehog Inhibitors (HHIs)

Abstract not available

A Melodic Contour Repeatedly Experienced by Human Near-Term Fetuses Elicits a Profound Cardiac Reaction One Month after Birth

Human hearing develops progressively during the last trimester of gestation. Near-term fetuses can discriminate acoustic features, such as frequencies and spectra, and process complex auditory streams. Fetal and neonatal studies show that they can remember frequently recurring sounds. However, existing data can only show retention intervals up to several days after birth.Here we show that auditory memories can last at least six weeks. Experimental fetuses were given precisely controlled exposure to a descending piano melody twice daily during the 35(th), 36(th), and 37(th) weeks of gestation. Six weeks later we assessed the cardiac responses of 25 exposed infants and 25 naive control infants, while in quiet sleep, to the descending melody and to an ascending control piano melody. The melodies had precisely inverse contours, but similar spectra, identical duration, tempo and rhythm, thus, almost identical amplitude envelopes. All infants displayed a significant heart rate change. In exposed infants, the descending melody evoked a cardiac deceleration that was twice larger than the decelerations elicited by the ascending melody and by both melodies in control infants.Thus, 3-weeks of prenatal exposure to a specific melodic contour affects infants 'auditory processing' or perception, i.e., impacts the autonomic nervous system at least six weeks later, when infants are 1-month old. Our results extend the retention interval over which a prenatally acquired memory of a specific sound stream can be observed from 3-4 days to six weeks. The long-term memory for the descending melody is interpreted in terms of enduring neurophysiological tuning and its significance for the developmental psychobiology of attention and perception, including early speech perception, is discussed

Primary Analysis of Phase 2 Results for Cemiplimab in Patients (pts) with Locally Advanced Basal Cell Carcinoma (laBCC) who Progress on or are Intolerant to Hedgehog Inhibitors (HHIs)

Abstract not available