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Beitrag zur Käferfauna Griechenlands : sechstes Stück: Malacodermata, Cleridae, Ptinidae, Anobiadae
(1859)
Simple Summary
Endometrial cancer is the most frequent gynecologic tumor in developed countries. Obesity is an established risk factor for this disease. This work provides an overview of pathophysiological interactions and pathways in obese women initiating tumorigenesis. Furthermore, the clinical impact of adiposity on the treatment of endometrial cancer is discussed as well therapeutic and preventive options.
Abstract
Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 kg/m2 is increasing worldwide, correspondingly leading to a higher prevalence of EC. Understanding the adipose tissue as an endocrine organ, elementary pathophysiological pathways of tumorigenesis have been revealed. This includes the fundamental role of hyperglycemia, insulin resistance, and hyperestrogenemia, as well as interactions with a chronic proinflammatory microenvironment. Therapeutic options potentially include metformin or bariatric surgery. Moreover, changes in individual lifestyle such as weight reduction, physical activity, and an awareness of healthy nutrition are effective in preventing the disease.
Ich habe das Buch mit Interesse an den historischen Vorgängen gelesen, gegen Ende auch mit einer gewissen Spannung hinsichtlich des Ausganges der Aufarbeitungsgeschichte, aber „packend“ fand ich den Krebsgang nicht. Grass arbeitet sich langsam an das heran, was im Zentrum der Novelle stehen sollte, die Torpedierung der „Wilhelm Gustloff“, und umgibt die lange aufgesparte Vergegenwärtigung dieses Ereignisses zugleich mit zwei intermittierend sich entfaltenden Rahmenerzählungen: einer historischen, die über die Vorgeschichte des Zentralereignisses informiert, und einer aktuellen, die den späteren Umgang mit diesem schrecklichen dramatisiert.
ONE NIGHT IN PARIS entstand am 9. und 10. Oktober 2001 im Palais Omnisport, Paris. Zwar wird nur der 10. Oktober als Aufnahmedatum angegeben, der Song It Doesn’t Matter Two, der im Film zu sehen ist, wurde jedoch nur am 9. Oktober gespielt und zeigt somit, dass Material von beiden Auftritten verwendet wurde. An den fast zweistündigen Konzertmitschnitt schließt sich umfangreiches Zusatzmaterial an, unter anderem Interviews und Hintergrundinformationen über die Vorbereitung und Umsetzung der Tour.
Solar photovoltaics (PV) panels in combination with batteries are often proposed as a solution to provide stable power supply in rural areas. PV generation is mostly dominated by the solar diurnal cycle and has, in some countries, already started to have influence on the daily price distribution on the electricity market.
In this work, we study the performance and optimisation of rural PV-battery hybrid systems in a future renewable Polish power system. We use data on generation potentials to study PV and battery deployment. Together with a power system optimisation and dispatch model for the Polish power system, we study market values when selling at the national market for different CO2 price scenarios. We show that optimal orientations with respect to tilt/azimuth are subject to change as the PV share grows and that the benefit from batteries grows for higher shares of renewables.
In this study, we investigate the wealth decumulation decision from the perspective of a retiree who is averse to the prospect of fully annuitizing her accumulated savings. We field a large online survey of hypothetical product choices for phased drawdown offerings and annuities. While the demand for annuities remains low in our sample, we find significant demand for phased withdrawal products with equity-based asset allocations and flexible payout structures. Consistent with the product choice, the most important self-reported considerations for the wealth decumulation decision are low default risk in the products they purchase, the size of the withdrawal rates, and flexibility in the timing of their withdrawal. As determinants of the decision of how much wealth individuals are willing to draw down, we identify consumers’ attitudes towards future economic conditions, the extent to which they are protected against longevity risk, and their desire to leave bequests. Policy implications are discussed.
Rezensionen zu: Richard Wagners politische Theologie : Kunst zwischen Revolution und Religion / Peter Hofmann. - Paderborn : Verl. Ferdinand Schöningh, 2003. - 320 S., ISBN 3-506-73929-8, 39,80 Euro Richard Wagner : Ahasvers Wandlungen / Dieter Borchmeyer. - Frankfurt am Main [u.a.] : Insel Verl., 2002. - 647 S., ISBN 3-458-17135-5, 44,90 Euro.
Monoacylglycerol lipase (MGL) expressed in cancer cells influences cancer pathogenesis but the role of MGL in the tumor microenvironment (TME) is less known. Using a syngeneic tumor model with KP cells (KrasLSL-G12D/p53fl/fl; from mouse lung adenocarcinoma), we investigated whether TME-expressed MGL plays a role in tumor growth of non-small cell lung cancer (NSCLC).
In sections of human and experimental NSCLC, MGL was found in tumor cells and various cells of the TME including macrophages and stromal cells. Mice treated with the MGL inhibitor JZL184 as well as MGL knock-out (KO) mice exhibited a lower tumor burden than the controls. The reduction in tumor growth was accompanied by an increased number of CD8+ T cells and eosinophils. Naïve CD8+ T cells showed a shift toward more effector cells in MGL KOs and an increased expression of granzyme-B and interferon-γ, indicative of enhanced tumoricidal activity. 2-arachidonoyl glycerol (2-AG) was increased in tumors of MGL KO mice, and dose-dependently induced differentiation and migration of CD8+ T cells as well as migration and activation of eosinophils in vitro.
Our results suggest that next to cancer cell-derived MGL, TME cells expressing MGL are responsible for maintaining a pro-tumorigenic environment in tumors of NSCLC.
Hintergrund: Eine adäquate Anpassung der Glukokortikoidsubstitution an unterschiedliche Situationen ist essenziell für Leistungsfähigkeit und Lebensqualität von Patienten mit Nebennierenrindeninsuffizienz (NNRI). Sie dient darüber hinaus der Vermeidung lebensbedrohlicher adrenaler Krisen.
Ziel der Arbeit: Verbesserung der Versorgung von Patienten mit Nebennierenrindeninsuffizienz.
Material und Methoden: Selektive Literaturrecherche unter besonderer Berücksichtigung neuerer Studien.
Ergebnisse: Eine optimale Glukokortikoidsubstitution hat das Ziel, die physiologischen Kortisolschwankungen möglichst genau nachzuahmen. Hier haben in den letzten Jahren Präparate mit veränderter Pharmakokinetik das Therapiespektrum erweitert. Im Vordergrund stehen eine adäquate Anpassung der Substitution in Stresssituationen sowie die Vermeidung und adäquate Behandlung adrenaler Krisen, die mit einer Inzidenz von 4,8 bis 8,3 Krisen pro 100 Patientenjahre auftreten und mit einer Mortalität von etwa 0,5 pro 100 Patientenjahre weiterhin eine tödliche Bedrohung darstellen.
Schlussfolgerung: Zur Verhinderung lebensbedrohlicher Nebennierenkrisen ist eine Schulung von Patienten, Angehörigen und insbesondere auch medizinischem Personal notwendig.
Rhythmic neural spiking and attentional sampling arising from cortical receptive field interactions
(2018)
Summary: Growing evidence suggests that distributed spatial attention may invoke theta (3-9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is however not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields elicits rhythmic multi-unit activity (MUA) at 3-6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RT) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at at theta frequencies. These findings suggest that theta-rhythmic neuronal activity arises from competitive receptive field interactions and that this rhythm may subserve attentional sampling.
Highlights:
* Center-surround interactions induce theta-rhythmic MUA of visual cortex neurons
* The MUA rhythm does not depend on small fixational eye movements
* Reaction time fluctuations lock to the neuronal rhythm under distributed attention
Growing evidence suggests that distributed spatial attention may invoke theta (3–9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is, however, not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields (RFs) elicits rhythmic multi-unit activity (MUA) at 3–6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RTs) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at theta frequencies. These findings show that theta rhythmic neuronal activity can arise from competitive RF interactions and that this rhythm may result in rhythmic RTs potentially subserving attentional sampling.
Sampling of information is thought to be an important aspect of explorative behaviour. Evidence for it has been gained in behavioural assessments of a variety of overt and covert cognitive domains, including sensation, attention, memory, eye movements and dexterity. A common aspect across many findings is that sampling tends to exhibit a rhythmicity at low frequencies (theta, 4–8 Hz; alpha, 9–12 Hz). Neurophysiological investigations in a wide range of species, including rodents, non-human primates and humans have demonstrated the presence of sampling related neural oscillations in a number of brain areas ranging from early sensory cortex, hippocampus to high-level cognitive areas. However, to assess whether rhythmic sampling represents a general aspect of exploratory behaviour one must critically evaluate the task parameters, and their potential link with neural oscillations. Here we focus on sampling during attentive vision to present an overview on the experimental conditions that are used to investigate rhythmic sampling and associated oscillatory brain activity in this domain. This review aims to (1) provide guidelines to efficiently quantify behavioural rhythms, (2) compare results from human and non-human primate studies and (3) argue that the underlying neural mechanisms of sampling can co-occur in both sensory and high-level areas.
Highlights
• Microstimulation of visual area V4 improves visual stimulus detection
• Effects of V4 microstimulation extend to the other hemifield
• Microstimulation effects are time dependent and consistent with attention dynamics
Summary
Neuronal activity in visual area V4 is well known to be modulated by selective attention, and there are reports on V4 lesions leading to attentional deficits. However, it remains unclear whether V4 microstimulation can elicit attentional benefits. To test this hypothesis, we performed local microstimulation in area V4 and explored its spatial and time dynamics in two macaque monkeys performing a visual detection task. Microstimulation was delivered via chronically implanted multi-electrode arrays. We found that microstimulation increases average performance by 35% and reduces luminance detection thresholds by −30%. This benefit critically depends on the onset of microstimulation relative to the stimulus, consistent with known dynamics of endogenous attention. These results show that local microstimulation of V4 can improve behavior and highlight the critical role of V4 for attention.
Although the first travels to America were largely motivated by material interests, the news about native peoples published in Europe by the travellers little by little influenced a conception of the world, which was still dominated by medieval traditions. In general, the experience of the alien was still described in the forms of the own, but gradually the empirical knowledge began to structure a new discourse. The author analyses the earliest books on voyages to Brazil in the middle of the l6th century by Hans Staden, Jean de Léry and André Thevet. He observes how they develop discursive orders of their own, trying to deal with strange phenomena. They mark a first step for Western thought in the process of creating a space for the alien, who really exists – in this case on the coast of Brazil.
Reintroductions of plant species are increasingly popular in conservation practice. Steppe grasslands contain many rare and endangered plant species that are potential objects for such reintroductions. Most reintroduction projects, however, can only target a restricted number of species, which raises the question of how species should be prioritised. Here, we present a method to select priority species for reintroduction based on species' characteristics that are widely used in conservation practice. We first determined the local species pool containing those vascular plant species that occurred both in our target region (Thuringia, Germany) and target habitat (steppe grasslands), yielding 369 species. With the help of an a priori filter that selected currently endangered species with limited distribution, 136 potential target species were determined. These potential target species had experienced stronger decline, had a narrower phytosociological amplitude and were more likely to be species of the Festuco-Brometea class and the Festucetalia valesiacae order than non-target species. Potential target species were then ranked by a points system based on ten conservation-relevant characteristics of the species from the categories "threat and protection status", "distribution and decline", and "habitat affiliation". In the ranking, six steppe grassland plant species (Astragalus exscapus, Bothriochloa ischaemum, Prunella laciniata, Pulsatilla pratensis subsp. nigricans, Scorzonera purpurea, and Seseli hippomarathrum) achieved the highest scores. An additional seven species not specifically characteristic for steppe grasslands also scored highly. A post hoc evaluation of these 13 highest scoring species based on additional conservation criteria left five species (Astragalus exscapus, Linum leonii, Orchis morio, Pulsatilla pratensis subsp. nigricans and Scorzonera purpurea) as species with highest priority for reintroductions and another five species as highly suitable for reintroductions. Associations between the ranking order and different ranking criteria revealed that a species’ threat and rarity in Thuringia and its protection status had the highest representation in the ranking, followed by threat in Germany, regional decline and habitat affiliation. In contrast, international threat and responsibility of Thuringia for its conservation had only low representation in the ranking, probably because these characteristics applied to only a few species. The ranking list gives a selection of species for reintroductions, which combined with additional information based on comprehensive local and floristic knowledge, allows the identification of the species with the highest priority. Our method can be transferred to other regions or habitat types.
The management of urban waste constitutes one of the major environmental challenges facing African cities in general and Cameroon in particular. Unprecedented population growth and changes in consumption patterns and lifestyles have led to increased waste generation. Municipal solid waste management efforts lag behind the rate of waste generation with attendant environmental and public health risks. The activities, the gender dynamics and politics at the pools of waste generation, particularly the households and markets largely influence the outcome of waste management strategies and policies. This book brings out the gender dimension of municipal solid waste generation and management in the City of Bamenda. It is hoped that the findings revealed and proposals made from the study will be employed by municipal authorities in Cameroon and beyond to enhance waste management efforts.
Faunistic spider collections in the Museum für Naturkunde Berlin: The collection of Erich Hesse
(2012)
The ‘Hesse collection’ of spiders (Araneae) and harvestmen (Opiliones) in the Museum für Naturkunde Berlin is documented. Biographical notes on Erich Hesse – a former arachnid curator at the museum (1921–1940) – are provided. The ‘Hesse collection’ was actually put together by other workers, and can be broadly divided into two parts. One comes from Bielinek (= Bellinchen) on the Polish side of the Oder Valley (West Pommerania); now part of the ‘Unteres Odertal’ National Park. This Bielinek material includes notable records of Heriaeus oblongus Simon, 1918 and Gibbaranea ullrichi (Hahn, 1835). The other part of the collection comes from Colbitz-Letzlinger Heide in Saxony-Anhalt, Germany. Notable here are Pistius truncatus (Pallas, 1772) and Philodromus buchari Kubcová, 2004; the latter representing the first record of this species for Saxony-Anhalt.
A female of the dwarf sheet spider Hahnia picta Kulczyński, 1897 was found in an old castle park in Berlin (Germany). All published records as well as unpublished records from Austria are listed and mapped. This species is rarely recorded. Its distribution is confined to Europe. H. picta seems to live exclusively under the bark of old deciduous trees.
The rare money spider Walckenaeria simplex Chyzer, 1894 was found in 2007 near the city of Meißen (Germany) on a rock overlooking the river Elbe. This is the northernmost occurrence of the species. W. simplex is distributed from Central to South Eastern Europe. The species is thermophilous and prefers wooded slopes with a southern exposition.
A glimpse of the tropics : spiders (Araneae) in the greenhouses of the Botanic Garden Berlin-Dahlem
(2008)
In a survey of the spider fauna in greenhouses of the Botanic Garden Berlin-Dahlem, 30 spider species were recorded. Two species are new to Europe: Theotima minutissima (Petrunkevitch, 1929) and Heteroonops spinimanus (Simon, 1891). T. minutissima is the first member of the family Ochyroceratidae reported from Europe. Oecobius navus Blackwall, 1859 is new to Central Europe. Triaeris stenaspis Simon, 1891, is recorded from Germany for the first time. Zodarion italicum (Canestrini, 1868) is new to eastern Germany. Despite the discovery of some species previously unknown to Germany, the spider fauna in the Botanic Garden consisted mainly of wellknown synanthropic species and common inhabitants of greenhouses. Several alien spiders recently found in greenhouses, garden centers and houses were not recorded in the Botanic Garden. The species composition of the exotic spider fauna in greenhouses seems to depend chiefly on the specific modes of acquisition of plants and plant substrate.
A female specimen of the cribellate spider species Badumna longinqua (L. Koch, 1867) was found in a 'do-it-yourself-store' in Berlin. The species is of Australian origin and has been introduced into New Zealand, Japan, Uruguay and California. This is the first record of a representative of the family Desidae from Europe. B. longinqua lives in and around houses and is apparently capable of establishing itself in Europe.
The increasing incidence of infected skin wounds poses a major challenge in clinical practice, especially when conventional antibiotic therapy fails. In this context, bacteriophages emerged as promising alternatives for the treatment of antibiotic-resistant bacteria. However, clinical implementation remains hampered by the lack of efficient delivery approaches to infected wound tissue. In this study, bacteriophage-loaded electrospun fiber mats were successfully developed as next-generation wound dressings for the treatment of infected wounds. We employed a coaxial electrospinning approach, creating fibers with a protective polymer shell, enveloping bacteriophages in the core while maintaining their antimicrobial activity. The novel fibers exhibited a reproducible fiber diameter range and morphology, while the mechanical fiber properties were ideal for application onto wounds. Further, immediate release kinetics for the phages were confirmed as well as the biocompatibility of the fibers with human skin cells. Antimicrobial activity was demonstrated against Staphylococcus aureus and Pseudomonas aeruginosa and the core/shell formulation maintained the bacteriophage activity for 4 weeks when stored at − 20 °C. Based on these promising characteristics, our approach holds great potential as a platform technology for the encapsulation of bioactive bacteriophages to enable the translation of phage therapy into clinical application.
Here, we report on 33 molluscan species from Miocene ’Calcari a Lucina’ hydrocarbon-seep deposits in northern Italy. Three new species are described: the chilodontaid gastropod Putzeysia diversii sp. nov., the lucinid bivalve Miltha (sensu lato) romaniae sp. nov., and Sisonia ultimoi sp. nov., a heterodont bivalve of uncertain taxonomic affinity. Fourteen species are described in open nomenclature. The common but enigmatic gastropod species Phasianema taurocrassa is here suggested to belong to the seguenzioid genus Cataegis. Most gastropod species are inhabitants of the deep-sea floor in general, and are not restricted (obligate) to sites of hydrocarbon-seepage. The gastropod Putzeysia diversii sp. nov. and the bivalve Sisonia ultimoi sp. nov. are the geologically oldest members of their genera known to date. While the genus Putzeysia is geographically restricted to the NE Atlantic Ocean and the Mediterranean Sea, Sisonia ultimoi sp. nov. represents another link of the Miocene Mediterranean seep fauna to that of the central Indo-West Pacific Ocean.
EU financial integration : is there a 'Core Europe'? ; evidence from a cluster-based approach
(2005)
Numerous recent studies, e.g. EU Commission (2004a), Baele et al. (2004), Adam et al.(2002), and the research pooled in ECB-CFS (2005), Gaspar, Hartmann, and Sleijpen(2003), have documented progress in EU financial integration from a micro-level view.This paper contributes to this research by identifying groups of financially integratedcountries from a holistic, macro-level view. It calculates cross-sectional dispersions, andinnovates by applying an inter-temporal cluster analysis to eight euro area countries for the period 1995-2002. The indicators employed represent the money, government bond and credit markets. Our results show that euro countries were divided into two stable groups of financially more closely integrated countries in the pre-EMU period. Back then, geographic proximity and country size might have played a role. This situation has changed remarkably with the euro's introduction. EMU has led to a shake-up both in the number and composition of groups. The evidence puts a question mark behin d using Germany as a benchmark in the post-EMU period. The ¯ndings suggest as well that ¯nancial integration takes place in waves. Stable periods and periods of intense transition alternate. Based on the notion of 'maximum similarity', the results suggest that there exist 'maximum similarity barriers'. It takes extraordinary events, such as EMU, to push the degree of ¯nancial integration beyond these barriers. The research encourages policymakers to move forward courageously in the post-FSAP era, and provides comfort that the substantial di®erences between the current and potentially new euro states can be overcome. The analysis could be extended to the new EU member countries, to the global level, and to additional indicators.
Im Jahr 1993 wurde auf ehemaligen Ackerflächen in der Umgebung des Naturschutzgebiets „Garchinger Heide“ mit der Neuanlage von Kalkmagerrasen begonnen. In den Jahren 2001 bis 2004 wurde der Einfluss verschiedener Renaturierungsmaßnahmen (Bodenabtrag, Mähgutübertragung) auf die Vegetation untersucht und ein Vergleich mit Referenzflächen im Naturschutzgebiet durchgeführt. Trotz hoher P- und K-Gehalte der Böden ist der Phytomasseertrag auf Renaturierungsflächen ohne Bodenabtrag so niedrig, dass die Flächen als Magerrasen bezeichnet werden können. Sowohl die Gesamtartenzahl der Phanerogamen als auch die Anzahl der Magerrasenarten (überwiegend Festuco-Brometea-Arten) als Zielarten der Renaturierung sind auf Flächen mit Mähgut noch deutlich höher als auf Flächen ohne Mähgut, auf denen Molinio-Arrhenatheretea-Arten und Ruderalarten dominieren. Die γ-Diversität der Phanerogamen ist in den nie umgebrochenen Magerrasen der Garchinger Heide zwar niedriger, die Anzahl der Magerrasenarten aber höher als auf den Renaturierungsflächen ohne Bodenabtrag. Hinsichtlich der α-Diversität der Phanerogamen, die auf 0,01 m2 bis 100 m2 großen Aufnahmeflächen untersucht wurde, zeigen sich kaum signifikante Unterschiede zwischen ursprünglichen und neu angelegten Magerrasen. Die Anzahl der Magerrasenarten ist jedoch auf den meisten der untersuchten Maßstabsebenen auf den Renaturierungsflächen niedriger als im Naturschutzgebiet. Bei den Kryptogamen ist bei gleicher γ-Diversität sowohl die α-Diversität als auch die Anzahl der Magerrasenarten in den ursprünglichen Magerrasen höher als in den neu angelegten.
Die Ergebnisse zeigen, dass die Ermittlung von Artenzahlen ohne Angaben zur Artenzusammensetzung oder zur Anwesenheit von Zielarten nicht ausreicht, um den Erfolg von Naturschutz- und Renaturierungsmaßnahmen zu beurteilen. Die Magerrasenarten als Zielarten der Renaturierung sind dagegen gut als Indikatorartengruppe im Rahmen von Erfolgskontrollen geeignet.
We give a report of the fourth annual symposium of the Dry Grassland Working Group, which was organized in conjunction with the second workshop ‘Floristics and geobotany - Contributions to applied questions’, from 6 to 8 Sept. 2007 in Freising-Weihenstephan. The symposium was entitled ‘Restoration and spontaneous establishment of dry and semi-dry grasslands at traditional and urban-industrial sites’. Additionally, the aims of the Dry Grassland Working Group are shortly outlined and the next symposia of both groups are announced.
Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.
Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.
Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.
Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.
Les larves de cécidomyes ont depuis longtemps attiré l'attention sur elles soit à cause des déformations que la plupart produisent sur les plantes, soit a cause du dégât occasionné par plusieurs autres. Il doit encore en être de même si nous considérons la forme et l'organisation de leur corps. Pour nous en convaincre, voyons d'abord des larves qui, n'occasionnant ni cécidie ni dégât, semblent à première vue n'avoir aucun droit à notre intérêt. Celles du genre Rubsaamenia m., demeurées inconnues jusqu'ici, nous en fourniront un premier exemple.
En passant par Francfort, sa ville natale, le 23 août 1797, Goethe fait la découverte d'"environ deux cents gravures satiriques françaises" comme il l'écrit le lendemain à Schiller. Il s'agit de gravures faites il y a deux ou trois ans à Paris, la dernière au mois de mars 1797. [...] De toute façon Goethe choisit 55 de ces gravures, les "schématise" (ibid.), comme il dit lui-même, et en donne une brève description. Résultat: le manuscrit "Recension einer Anzahl französischer satyrischer Kupferstiche" que son secrétaire du nom de Geist recopie sous la dictée de son maître.
Aims: Somatic mutations in haematopoietic stem cells can lead to the clonal expansion of mutated blood cells, known as clonal haematopoiesis (CH). Mutations in the most prevalent driver genes DNMT3A and TET2 with a variant allele frequency (VAF) ≥ 2% have been associated with atherosclerosis and chronic heart failure of ischemic origin (CHF). However, the effects of mutations in other driver genes for CH with low VAF (<2%) on CHF are still unknown.
Methods and results: Therefore, we analysed mononuclear bone marrow and blood cells from 399 CHF patients by deep error-corrected targeted sequencing of 56 genes and associated mutations with the long-term mortality in these patients (3.95 years median follow-up). We detected 1113 mutations with a VAF ≥ 0.5% in 347 of 399 patients, and only 13% had no detectable CH. Despite a high prevalence of mutations in the most frequently mutated genes DNMT3A (165 patients) and TET2 (107 patients), mutations in CBL, CEBPA, EZH2, GNB1, PHF6, SMC1A, and SRSF2 were associated with increased death compared with the average death rate of all patients. To avoid confounding effects, we excluded patients with DNMT3A-related, TET2-related, and other clonal haematopoiesis of indeterminate potential (CHIP)-related mutations with a VAF ≥ 2% for further analyses. Kaplan–Meier survival analyses revealed a significantly higher mortality in patients with mutations in either of the seven genes (53 patients), combined as the CH-risk gene set for CHF. Baseline patient characteristics showed no significant differences in any parameter including patient age, confounding diseases, severity of CHF, or blood cell parameters except for a reduced number of platelets in patients with mutations in the risk gene set in comparison with patients without. However, carrying a mutation in any of the risk genes remained significant after multivariate cox regression analysis (hazard ratio, 3.1; 95% confidence interval, 1.8–5.4; P < 0.001), whereas platelet numbers did not.
Conclusions: Somatic mutations with low VAF in a distinct set of genes, namely, in CBL, CEBPA, EZH2, GNB1, PHF6, SMC1A, and SRSF2, are significantly associated with mortality in CHF, independently of the most prevalent CHIP-mutations in DNMT3A and TET2. Mutations in these genes are prevalent in young CHF patients and comprise an independent risk factor for the outcome of CHF, potentially providing a novel tool for risk assessment in CHF.
Electric stimulation of the auditory nerve via cochlear implants has made the treatment of sensory deafness possible. Advanced signal processing and stimulation paradigms have led to continuously improved results in speech understanding. Consequently, indication criteria have been extended to patients with profound and severe-to-profound hearing loss and limited speech understanding with conventional acoustic amplification.
Outside this group, a considerable number of patients presents with rather wellpreserved, low frequency hearing of 30-60 dB up to 1 kHz, but severe loss in the mid to high frequency range of more than 60-70 dB. Monosyllabic word scores in these patients do not generally exceed 35%, due to missing consonant information. But, even increasing the audibility of these high frequencies by acoustic amplification still has very limited efficiency for discriminating speech, and therefore, these patients obtain only minor benefit from conventional hearing aids. On the other hand, standard cochlear implantation would carry a high risk of causing complete hearing loss. This situation has led to considering a combination of both modes of stimulation for these patients who are on the borderline between hearing aids and cochlear implant.
In our present model, the surviving low frequency region of the cochlea could still be stimulated acoustically-combined with additional electrical stimulation of the impaired mid and high frequency region of the cochlea.
Several questions still have to be answered with regard to combined electric and acoustic stimulation (EAS). The possible interaction of electric and acoustic stimuli on the different levels off the auditory system is a major issue. Animal experiments clearly demonstrate that tuning properties of auditory neurons, in response to acute acoustic stimulation, are essentially preserved in the presence of electric stimulation even at high levels of electric stimulation, and that chronic electric stimulation of tie intact inner ear does not have a significant effect on the compound action potentials (CAP) thresholds or inner ear function.
In a previous report, we were able to show that this combined F.A.S of the auditory system is possible in humans, and that it has a synergistic effect on speech understanding. Further major issues regard the surgical feasibility and reproducibility of cochlear implantation with the preservation of residual hearing.
Encouraged by our findings, a clinical study was initiated on the application of EAS. So far, seven adults have been included in this study. In addition, one child has been implanted outside the study.
Es mag sein, dass sich die japanische Kultur – ganz abgesehen von der Schrift – nicht leicht lesen lässt. Aber warum denn nicht? Warum soll uns die reizvolle Erfahrung erspart bleiben, dass ein wirtschaftlich und technologisch ebenbürtiger Partner der Weltgesellschaft sein Niveau auf einem andern Weg, aufgrund einer verschiedenen sozialen Kultur erreicht hat? Dass sich vermeintliche Universalien – Natur, Liebe, Religion, Familie, Individualität, Bindung, Freiheit – auch ganz anders buchstabieren und in stark abweichender Besetzung bis in 21. Jahrhundert mit Erfolg halten lassen? Warum eigentlich sollen wir nicht besser lesen lernen?