Environmental Risk of Pesticides for Fish in Small- and Medium-Sized Streams of Switzerland.

This study assessed the acute and chronic risk of pesticides, singly and as mixtures, for fish using comprehensive chemical data of four monitoring studies conducted in small- and medium-sized streams of Switzerland between 2012 and 2018. Pesticides were ranked based on single substance risk quotients and relative contribution to mixture risk. Concentrations of the pyrethroid insecticides, λ-cyhalothrin, cypermethrin and deltamethrin, and the fungicides, carbendazim and fenpropimorph, posed acute or chronic single substance risks. Risk quotients of eighteen additional pesticides were equal or greater than 0.1, and thirteen of those contributed ≥30% to mixture risk. Relatively few substances dominated the mixture risk in most water samples, with chronic and acute maximum cumulative ratios never exceeding 5 and 7, respectively. A literature review of toxicity data showed that concentrations of several pesticides detected in Swiss streams were sufficient to cause direct sublethal effects on fish in laboratory studies. Based on the results of our study, we conclude that pesticides detected in Swiss streams, especially pyrethroid insecticides, fungicides and pesticide mixtures, pose a risk to fish health and can cause direct sublethal effects at environmental concentrations. Sensitive life stages of species with highly specialized life history traits may be particularly vulnerable; however, the lack of toxicity data for non-model species currently prevents a conclusive assessment across species

Improvement of farm ponds and watersheds for erosion control and wildlife production

November, 1938."Revision of Circular 361.

AMPA-15N - Synthesis and application as standard compound in traceable degradation studies of glyphosate

Stable isotope labeling of pollutants is a valuable tool to investigate their environmental transport and degradation. For the globally most frequently used herbicide glyphosate, such studies have, so far, been hampered by the absence of an analytical standard for its labeled metabolite AMPA-15N, which is formed during the degradation of all commercially available glyphosate isotopologues. Without such a standard, detection and quantitation of AMPA-15N, e.g. with LC-MS/MS, is not possible. Therefore, a synthetic pathway to AMPA-15N from benzamide-15N via the hemiaminal was developed. AMPA-15N was obtained in sufficient yield and purity to be used as a standard compound for LC-MS/MS analysis. Suitable MS-detection settings as well as a calibration using the internal standard (IS) approach were established for Fmoc-derivatized AMPA-15N. The use of different AMPA isotopologues as IS was complicated by the parallel formation of [M+H]+ and [M]+• AMPA-Fmoc precursor ions in ESI-positive mode, causing signal interferences between analyte and IS. We recommend the use of either AMPA-13C-15N, AMPA-13C-15N-D2 or a glyphosate isotopologue as IS, as they do not affect the linearity of the calibration curve. As a proof of concept, the developed analysis procedure for AMPA-15N was used to refine the results from a field lysimeter experiment investigating leaching and degradation of glyphosate-2-13C-15N. The newly enabled quantitation of AMPA-15N in soil extracts showed that similar amounts (0.05 - 0.22 mg·kg-1) of the parent herbicide glyphosate and its primary metabolite AMPA persisted in the topsoil over the study period of one year, while vertical transport through the soil column did not occur for either of the compounds. The herein developed analysis concepts will facilitate future design and execution of experiments on the environmental fate of the herbicide glyphosate

Influence of Soil Type on the Effects of Elevated Atmospheric CO2 and N Deposition on the Water Balance and Growth of a Young Spruce and Beech Forest

Sixteen open-top chambers, each equipped with two non-weighablegravity-drained lysimeter compartments, were used to investigate the impacts of elevated atmospheric carbon dioxide (CO2) concentration and nitrogen (N) deposition on the water relations and growth of young model forest ecosystems on two different types of soils. The same vegetation of a mixed spruce and beech overstorey and various herbs in the understorey was planted in all treatments on both soils. The soils were repacked on top of a drainage layer. Four combinations of treatments were applied in four replicates each: ambient (370 cm3 m-3) CO2 + low (7 kg N ha-1 a-1) N deposition, ambient CO2 + high(70 kg N ha-1 a-1) N deposition, elevated (590 cm3 m-3) CO2 + low N deposition, and elevated CO2 + high N deposition. After canopy closure, treatment effects on evapotranspiration and growth during the third year of study were very different for the two soils.On the acidic sandy loam, elevated CO2 enhanced growth(leaf biomass +21%, roots +27%) at reduced evapotranspiration (-9%). High N deposition increased aboveground growth even more strongly (+50%), but also increased evapotranspiration (+16%). Together, elevated CO2 and high N had a more than additive fertilizer effect on growth, while their effects on evapotranspirationcompensated. On the calcareous loamy sand, elevated CO2not only tended to enhance growth (leaf biomass +17%, roots +20%), but also increased evapotranspiration (+5%).On this soil, aboveground growth was stimulated by N only incombination with elevated CO2, but less than on the acidic soil, while evapotranspiration (-6.5%) and root growth into the subsoil (-54%) were decreased by increased N deposition at both CO2 concentrations, in contrast to the N treatments on the acidic sandy loam. The influence of the soil on the observed ecosystem responses canbe interpreted in terms of the concept of optimal resource allocatio

Salvage surgery for head and neck squamous cell carcinoma

n/

Therapeutic drug monitoring of rivastigmine and donepezil under consideration of CYP2D6 genotype-dependent metabolism of donepezil

Background: The efficacy of acetylcholinesterase inhibitors (AChE-I) might depend on blood concentration. While rivastigmine metabolism is independent of the cytochrome P450 system, its isoenzymes, especially CYP2D6, metabolize donepezil. CYP2D6 polymorphisms can cause altered enzyme activity resulting in lower or higher than expected drug concentrations of donepezil. Objective: We investigated correlations between clinical efficacy and serum concentrations of rivastigmine and donepezil under special consideration of CYP2D6 genotype or gene dose-dependent metabolism of donepezil. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography - tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR) and allele-specific PCR were performed to assess CYP2D6 genotype and gene dose. Results: Patients treated with rivastigmine (n=28) or donepezil (n=48) were included in the study. Both gene dose and metabolism type significantly predicted the level of donepezil serum concentration (p=0.019 and p=0.013, respectively). In the rivastigmine group, changes of the word list delayed recall subtest before treatment and under stable medication were significantly associated with rivastigmine serum levels (beta=0.465;p=0.018). Drug serum concentrations were outside the recommended range in a substantial percentage of participants, which might have contributed to poor correlations between changes in cognitive measures and drug concentrations. Donepezil serum concentrations significantly depended on CYP2D6 gene dose. Conclusion: Testing AChE-I serum concentration should be considered in patients without clinical response to treatment or those with severe side effects. Patients with donepezil drug levels outside the recommended range might additionally profit from CYP2D6 genotyping or treatment with an AChE-I independent of CYP metabolism

Aquatic Fungi: A Disregarded Trophic Level in Ecological Risk Assessment of Organic Fungicides

Freshwater fungi are a diverse group of organisms and fulfill important functions in the food web dynamics of surface water ecosystems. Ascomycetic and basidiomycetic hyphomycetes play key roles in leaf litter breakdown in rivers and creeks, while parasitic chytrids are an important food source for small invertebrates in lakes. Field studies indicate that fungal communities are affected by fungicides at environmentally relevant concentrations. However, despite their ecological importance, freshwater fungi are currently not specifically addressed in the EU regulatory frameworks with respect to the protection of surface waters. Specifically, the prospective risk assessment of fungicides does not evaluate adverse effects on non-target aquatic fungi. This paper aims to describe important functions of freshwater fungi, provides an overview of adverse effect levels of fungicides on this organism group, and proposes to integrate the fungal community of freshwater ecosystems as an additional trophic level in the current fungicide risk assessment frameworks. Results of a literature review on the effects of fungicides on aquatic fungi revealed that information on the toxicity of fungicides to non-target aquatic fungi is limited. This is, in part, due to the lack of standardized bioassays using aquatic fungi as test species. Although there is an encouraging number of bioassays focusing on the degradation of dead organic material by hyphomycetes, studies on fungicide effects on other important ecological functions, like the control of algal blooms in lentic surface waters by parasitic chytrid fungi, or on mutualistic fungi living in the guts of aquatic arthropods are largely missing. Thus, the further development and standardized of different fungi bioassays is recommended

Serum Concentrations of Cholinesterase Inhibitors in Patients With Alzheimer's Dementia Are Frequently Below the Recommended Levels

Background: Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration of the respective AChE-I. Objective: In patients with mild to moderate Alzheimer's dementia, we measured serum concentrations of hepatically metabolized donepezil and renally excreted rivastigmine and investigated possible modifiers. Additionally, we looked at correlations between serum concentrations and efficacy for both drugs. Methods: Serum concentrations of donepezil and rivastigmine were measured by liquid chromatography – tandem mass spectrometry (LC-MS/MS). Real-time quantitative polymerase chain reaction (PCR). Allele specific PCR were performed to determine CYP2D6 genotype and gene dose. Clinical efficacy was assessed by changes of the subtest wordlist delayed recall of the Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). Results: Sixty-seven patients treated with a stable dosage of donepezil 10 mg (n=41) or rivastigmine 9.5 mg (n=26) were included. Mean serum concentration of donepezil and rivastigmine were 41.2 and 6.5 ng/ml, respectively. Serum concentrations were below the recommended range in 73% of the subjects in the donepezil group and in 65% of the participants in the rivastigmine group. When applying a dose-related reference, ranges 63% of patients in the donepezil group and 32% in the rivastigmine group had concentrations below the expected range. Gene dose, sex, and duration of treatment significantly predicted donepezil serum concentration (p=0.046, p=0.001, p=0.030 respectively). Only for rivastigmine did the serum concentration significantly contribute to the regression model predicting changes on the subtest word list delayed recall (β=0.472; p=0.019). Conclusions: Serum concentrations of about two thirds of the patients were below the recommended range. When not looking at absolute values but at the dose-related reference ranges, these numbers improved but still 32%, respectively 63% of patients had low serum concentrations. High serum concentrations of rivastigmine predicted clinical response to cognition. Therapeutic drug monitoring might help to identify the cause of poor clinical response to cognition and behavioral and psychological symptoms in patients with AChE-I treatment

Zur Integration neugegründeter Blaue-Liste-Institute in die deutsche Wissenschaftslandschaft: ausgewählte Befunde einer empirischen Untersuchung

"Im Zuge der Transformation der ostdeutschen Wissenschaft wurden 1992 in den Neuen Bundesländern auf Empfehlung des Wissenschaftsrates im Bereich der außeruniversitären Forschung über 50 Forschungsinstitute neu gegründet, darunter 34, d.h. zu fast 70 Prozent Institute der 'Blauen Liste'. Die Neugründung von Instituten im Bereich der außeruniversitären Forschung war Teil des alle Sektoren des Wissenschaftssystems, also auch die Industrie- und die Hochschulforschung umfassenden 'Institutionentransfers' nach bundesdeutschen Vorbild in Richtung Ost; er führte jedoch in keinem dieser Bereiche zu einer reinen Kopie der westdeutschen Forschungslandschaft. Mit der formellen Institutsgründung begannen für jedes dieser Institute komplexe Prozesse der internen Organisationsentwicklung und der Integration in die deutsche Wissenschaftslandschaft. Diese durch den Institutionentransfer ausgelösten Integrationsprozesse sowie die durch die Verschränkung interner und externer Integrationsprozesse bestimmten spezifischen Entwicklungspfade der Institute sind Gegenstand des seit 1994 durch die DFG geförderten und von der Forschungsgruppe Wissenschaftsstatistik des WZB bearbeiteten Projektes zur Integration ausgewählter ostdeutscher Institute der Blauen Liste. Im Beitrag werden Aspekte zur Fragestellung des Projektes sowie zur Vorgehensweise und ausgewählte empirische Zwischenergebnisse der zu vier Blaue-Liste-Instituten durchgeführten Fallstudien zur Diskussion gestellt. Es zeigt sich, daß das Tempo nahezu aller Integrationsprozesse dabei entscheidend durch die fachliche Profilierung beeinflußt wird. Diese wird jedoch in den meisten Instituten und in vielen ihrer Abteilungen durch eine Reihe von externen und internen Faktoren verzögert. Diese Verzögerungen sowie Umprofilierungen, die nicht an frühere Arbeiten anschließen, hemmen die interne und die externe Integration der Institute, so daß davon ausgegangen werden kann, daß die heute manifesten oder absehbaren Integrationsprobleme frühestens gegen Ende dieses Jahrhunderts überwunden sein werden, d.h. insgesarnt fast 10 Jahre benötigen." (Autorenreferat