Concept for a Time-of-Flight Small Angle Neutron Scattering Instrument at the European Spallation Source

A new Small Angle Neutron Scattering instrument is proposed for the European Spallation Source. The pulsed source requires a time-of-flight analysis of the gathered neutrons at the detector. The optimal instrument length is found to be rather large, which allows for a polarizer and a versatile collimation. The polarizer allows for studying magnetic samples and incoherent background subtraction. The wide collimation will host VSANS and SESANS options that increase the resolution of the instrument towards um and tens of um, respectively. Two 1m2 area detectors will cover a large solid angle simultaneously. The expected gains for this new instrument will lie in the range between 20 and 36, depending on the assessment criteria, when compared to up-to-date reactor based instruments. This will open new perspectives for fast kinetics, weakly scattering samples, and multi-dimensional contrast variation studies.Comment: 18 pages, 10 figure

Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 14(1), (2019):e0204193, doi: 10.1371/journal.pone.0204193.The resilience of regeneration in vertebrates is not very well understood. Yet understanding if tissues can regenerate after repeated insults, and identifying limitations, is important for elucidating the underlying mechanisms of tissue plasticity. This is particularly challenging in tissues, such as the nervous system, which possess a large number of terminally differentiated cells and often exhibit limited regeneration in the first place. However, unlike mammals, which exhibit very limited regeneration of spinal cord tissues, many non-mammalian vertebrates, including lampreys, bony fishes, amphibians, and reptiles, regenerate their spinal cords and functionally recover even after a complete spinal cord transection. It is well established that lampreys undergo full functional recovery of swimming behaviors after a single spinal cord transection, which is accompanied by tissue repair at the lesion site, as well as axon and synapse regeneration. Here we begin to explore the resilience of spinal cord regeneration in lampreys after a second spinal transection (re-transection). We report that by all functional and anatomical measures tested, lampreys regenerate after spinal re-transection just as robustly as after single transections. Recovery of swimming, synapse and cytoskeletal distributions, axon regeneration, and neuronal survival were nearly identical after spinal transection or re-transection. Only minor differences in tissue repair at the lesion site were observed in re-transected spinal cords. Thus, regenerative potential in the lamprey spinal cord is largely unaffected by spinal re-transection, indicating a greater persistent regenerative potential than exists in some other highly regenerative models. These findings establish a new path for uncovering pro-regenerative targets that could be deployed in non-regenerative conditions.The authors would like to thank Dr. Cristina Roman-Vendrell and Louie Kerr, Director of the Central Microscopy Facility at the MBL, for technical support. We also thank Dr. Juan Diaz-Quiroz for helpful comments on the manuscript. EG was supported in part by an NSF REU Award (#1659604: Biological Discovery in Woods Hole at the Marine Biological Laboratory)

Microplastics in Limnic Ecosystems - Investigation of Biological Fate and Effects of Microplastic Particles and Associated Contaminants in Zebrafish (Danio rerio)-

Given the continually increasing global polymer production, environmental pollution from plastic debris has been widely perceived as an ecological threat with potentially adverse (eco-)toxicological impacts on various species and ecosystems. Especially small fragments of plastic debris measuring 1 ≤ 1000 µm in size − so-called microplastics (MPs) − can pose a risk to biota by physical or chemical hazards due to ingestion, sorption and transfer of anthropogenic environmental pollutants (e.g., pesticides, polycyclic aromatic hydrocarbons, pharmaceuticals). In recent years, there has been extensive research on the impact of streams and rivers as main entry routes for MPs into the marine environment. However, the evidence of adverse effects caused by the intake of MPs and the transfer of contaminants sorbed to MPs into freshwater ecosystems is still not conclusively documented. Therefore, this thesis addressed the impact of microplastic particles in limnic ecosystems by investigating the biological fate and effects of MPs and associated anthropogenic pollutants on different life stages of zebrafish (Danio rerio). To this end, effects of two common environmental pollutants (benzo(k)fluoranthene, chlorpyrifos) and two synthetic polymers (polystyrene, polymethyl methacrylate) were investigated with regard to alterations of complementary biomarkers during acute and chronic exposure, as well as the trophic transfer of MPs and MP-sorbed contaminants from invertebrate organisms to zebrafish and acute toxic effects of MPs pre-exposed in a natural aquatic ecosystem. Overall, the sorption of both anthropogenic pollutants to MPs could be confirmed under various exposure scenarios. In contrast to recent study results, no adverse effects were observed when zebrafish were exposed to clean, pristine polystyrene and polymethyl methacrylate. The ingestion of MPs was documented in the gastrointestinal tract of zebrafish and did not induce any physiological impairment. The uptake of both pollutants was verified for all investigated species by GC-MS and fluorescence measurements. In the acute exposure scenario using the fish embryo toxicity test (FET), zebrafish embryos displayed sublethal effects and morphological deformities related to the underlying mode of action of benzo(k)fluoranthene and chlorpyrifos. Exposure to MP-associated contaminants significantly reduced malformations and attenuated biomarker responses of acetylcholine esterase activity and CYP450 induction and hence indicated a reduced bioavailability of both pollutants for zebrafish embryos. Chronic exposure of adult zebrafish to both types of MPs and pollutants was designed to assess the potential impact of long-term exposure and possible bioaccumulation of these contaminants of emerging concern. However, exposure to MP-sorbed pollutants failed to alter biomarker responses over the prolonged experimental period. In addition, a novel approach was applied to monitor the uptake of benzo(k)fluoranthene in the intestinal epithelium using confocal laser scanning microscopy. However, no significant bioaccumulation or biotransformation of benzo(k)fluoranthene and chlorpyrifos in brain and liver tissue could be demonstrated using ultra performance liquid chromatography coupled with fluorescence detection and with a high-resolution mass spectrometer (UPLC-FLD/HRMS). In order to address the possible vector effects of MPs, the transfer of benzo(k)fluoranthene and polymethyl methacrylate particles in a simplified limnic food web were investigated, consisting of zooplankton (Daphnia magna), sediment-dwelling invertebrates (Chironomus riparius larvae) and zebrafish as highlevel predator. However, the trophic transfer of benzo(k)fluoranthene via MPs could not be confirmed by a combination of highly sensitive fluorescence tracking using CLSM, hepatic CYP450 induction, and advanced chemical-analytical methods. To account for the demand for environmentally relevant exposure scenarios and to improve risk assessment of MPs, a mixture of the most commonly used synthetic polymers (polyethylene, polypropylene, polystyrene, polyvinyl chloride) was exposed in a well-monitored surface water body. To evaluate the potential transfer of hazardous pollutants under natural conditions, the toxicity of the MP mixture was assessed in terms of acute toxic effects (FET), potential neurotoxic effects (AChE activity, larval visual motor response test) and effects of dioxin-like substances (EROD assay) using zebrafish embryos. In conclusion, the exposed MP mixture did not elicit significantly different effects than the natural particles from sediment and suspended matter samples. Eventually, it could only be confirmed that MPs could act as carriers for environmental contaminants following ingestion by various organisms. However, increased deleterious effects of MP-sorbed contaminants on various sensitive life stages of zebrafish could not be corroborated by acute or prolonged exposure, trophic transfer, or natural exposure. The findings suggest that the sorption of pollutants to MPs is more likely to reduce the bioavailability as a result of slow desorption within the organism. Although, MPs offer an alternative exposure route for aquatic organisms via ingestion. Even chronic exposure at environmentally relevant concentrations did not induce bioaccumulation of both highly lipophilic substances in zebrafish tissues. Lastly, the sorption behavior of MPs under realistic environmental exposure conditions was more likely to approximate the behavior of natural particles. Consequently, MPs might pose only a limited risk to limnic communities, especially with regard to the comparatively small fraction of plastic particles in freshwater ecosystems compared to the multitude of naturally occurring (a)biotic particles

Use of neuraminidase inhibitors in primary health care during pandemic and seasonal influenza between 2009 and 2013: Outpatient influenza antiviral treatment

International audienceBACKGROUND:In a context of controversy about influenza antiviral treatments, this study assessed primary health-care physicians' prescription of neuraminidase inhibitors (NIs) in France during pandemic and seasonal influenza between 2009 and 2013.METHODS:This observational study, using data recorded in three national databases, estimated the rate of NI prescription among influenza-like illness (ILI) patients seen in GP and paediatrician consultations, and determined factors associated with this prescription according to a multivariate analysis. NI delivery by pharmacists was also evaluated.RESULTS:Rates of NI prescription were estimated to be 61.1% among ILI patients with a severe influenza risk factor seen in GP consultation during the A(H1N1)pdm2009 pandemic versus an average rate of 25.9% during the three following seasonal influenza epidemics. Factors associated with NI prescription were a chronic disease in patients under 65 years (OR 14.85; 95% CI 13.00, 16.97) and in those aged 65 and older (OR 7.54; 5.86, 9.70), an age ≥65 years in patients without chronic disease (OR 1.35; 1.04, 1.74), a pregnancy (OR 10.63; 7.67, 15.76), obesity (OR 4.67; 3.50, 6.22) and a consultation during the pandemic A(H1N1)pdm2009 (OR 3.19; 2.93, 3.48). The number of antiviral treatments delivered by pharmacists during the A(H1N1)pdm2009 pandemic was 835 per 100,000 inhabitants, and an average of 275 per 100,000 inhabitants during the three following seasonal influenza epidemics.CONCLUSIONS:Although physicians seem to follow the recommended indications for NIs in primary health-care practice, this study confirms the low rate of NI prescription to ILI patients with a severe influenza risk factor, especially during seasonal epidemics

Water as a Refrigerant in Centrifugal Compressor Cooling Systems for Industrial Applications

As a consequence of the F-gas regulation R404A is no longer a viable option for commercial refrigeration applications. Therefore, this paper focuses on natural refrigerants. There are a few alternatives like carbon dioxide, which has an efficiency loss with increasing environment temperatures. A promising option is the combination of a carbon dioxide process with a chiller using water as refrigerant. Two types of interconnection seem to make energy sense. On the one hand, the interconnection as a cascade, whereby the complete heat of condensation is given off to the water chiller, on the other hand the subcooling of transcritical CO2 after the gas cooler. Both types of interconnection result in optimized operating parameters for the CO2 process. These are examined more closely, and finally, the annual COP values are compared with the standard systems

Efficiency Enhancement By Subcooling The Carbon Dioxide Process With Water As Refrigerant

As a consequence of the F-Gas regulation R404A is no longer an option for commercial refrigeration applications. Therefore, this paper focuses on natural refrigerants. There are a few options like carbon dioxide, which has an efficiency loss with increasing ambient temperatures. A promising option is subcooling of the carbon dioxide process with a chiller using water as the refrigerant. This will result in a new optimized high pressure of the carbon dioxide process depending on the ambient temperature. Finally the annual COP values of the standard transcritical and subcooled system will be discussed

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

First-line treatment of metastatic breast cancer with the use of liposomal doxorubicin (Myocet®) in a female patient with ischaemic heart disease and cardiac dysrhythmia

Antracykliny są lekami o dużej skuteczności w leczeniu chorych z rozsianym rakiem piersi. Część pacjentek obciążonych kardiologicznie posiada przeciwwskazania do zastosowania tego typu leczenia, ze względu na ryzyko rozwinięcia się kardiotoksyczności. Opisany przypadek dotyczy pacjentki z chorobą niedokrwienną serca i zaburzeniami rytmu, u której zastosowano leczenie doksorubicyną liposomalną w pierwszej linii leczenia rozsianego raka piersi. Onkol. Prak. Klin. 2010; supl. A: A31–A32Anthracyclines are drugs characterised by high efficacy in the treatment of patients with metastatic breast cancer. However, this therapeutic approach is contraindicated in some of the female patients with a history of heart disease in view of the risk of cardiotoxicity. A case report is presented of a female patient with ischaemic heart disease and cardiac dysrhythmia receiving liposomal doxorubicin as part of the first-line treatment of metastatic breast cancer. Onkol. Prak. Klin. 2010; supl. A: A31–A3

Chemotherapy based on liposomal doxorubicin (Myocet®) in metastatic breast cancer after prior first-line treatment with anthracycline

Metastatic at diagnosis breast cancer occurs increasingly rarely, yet it remains a significant therapeutic problem. The abundance of available systemic treatment regimens and the possibility of applying different therapies pose before the physician a difficult task of employing the optimal treatment approach. At the same time, good therapeutic results and ever better tolerance for systemic treatment lead to female patients receiving a large number of chemotherapy lines. One of the options in recent years is the treatment with the use of liposomal doxorubicin. A case report is presented of a female patient who received secondline therapy with liposomal doxorubicin in combination with cyclophosphamide after prior treatment with anthracyclines. Onkol. Prak. Klin. 2010; supl. A: A28–A30Rozsiany w chwili rozpoznania rak piersi zdarza się coraz rzadziej, jednak ciągle stanowi poważny problem terapeutyczny. Mnogość dostępnych schematów leczenia systemowego i możliwość zastosowania różnych terapii stawiają przed lekarzem trudne zadanie zastosowania optymalnego schematu leczenia. Jednocześnie dobre efekty leczenia oraz coraz lepsza tolerancja leczenia systemowego powodują, że pacjentki są leczone wieloma liniami chemioterapii. Jedną z propozycji ostatnich lat jest leczenie z zastosowaniem liposomalnej doksorubicyny. Opisano przypadek pacjentki, u której przeprowadzono leczenie drugiej linii z zastosowaniem doksorubicyny liposomalnej w połączeniu z cyklofosfamidem po uprzednim leczeniu antracyklinami. Onkol. Prak. Klin. 2010; supl. A: A28–A3