The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PurposeTo determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics.Materials and methodsThis retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame.ResultsWe identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019).ConclusionPalonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs

Precise Characterization and Multiobjective Optimization of Low Noise Amplifiers

Although practically all function blocks of the satellite navigation receivers are realized using the CMOS digital integrated circuits, it is appropriate to create a separate low noise antenna preamplifier based on a low noise pHEMT. Such an RF front end can be strongly optimized to attain a suitable tradeoff between the noise figure and transducer power gain. Further, as all the four principal navigation systems (GPS, GLONASS, Galileo, and COMPASS) work in similar frequency bands (roughly from 1.1 to 1.7 GHz), it is reasonable to create the low noise preamplifier for all of them. In the paper, a sophisticated method of the amplifier design is suggested based on multiobjective optimization. A substantial improvement of a standard optimization method is also outlined to satisfy a uniform coverage of Pareto front. Moreover, for enhancing efficiency of many times repeated solutions of large linear systems during the optimization, a new modification of the Markowitz criterion is suggested compatible with fast modes of the LU factorization. Extraordinary attention was also given to the accuracy of modeling. First, an extraction of pHEMT model parameters was performed including its noise part, and several models were compared. The extraction was carried out by an original identification procedure based on a combination of metaheuristic and direct methods. Second, the equations of the passive elements (including transmission lines and T-splitters) were carefully defined using frequency dispersion of their parameters as Q, ESR, etc. Third, an optimal selection of the operating point and essential passive elements was performed using the improved optimization method. Finally, the s-parameters and noise figure of the amplifier were measured, and stability and third-order intermodulation products were also checked

Investigations on life-cycle and host specificity of the Malacosporea (Myxozoa)

Es ist bekannt, dass Parasiten der Klasse Malacosporea (Myxozoa) sowohl Fische als auch Süßwasserbryozoen infizieren, allerdings wurden die meisten Malacosporea bisher nur im Wirbellosenwirt beschrieben. Kenntnisse über Wirtsspektrum, Übertragungsmechanismen und innerartliche Unterschiede in der Empfänglichkeit gegenüber Malacosporea-Erregern sind bislang rar. Daher war es das Ziel dieser Dissertation Biologie und Lebenszyklen einiger Malacosporea-Parasiten intensiver zu untersuchen. Die Übertragung von T. brysalmonae auf Bryozoen war bisher nur mittels infizierter Bachforellen (Salmo trutta) erfolgreich. Daher wurde untersucht, ob neben Bachforellen möglicherweise andere Fischarten geeignete Wirte für T. bryosalmonae darstellen. Es konnte nachgewiesen werden, dass auch Bachsaiblinge (Salvelinus fontinalis) den Parasiten auf Bryozoen übertragen können. Im Gegensatz dazu lösten infizierte Regenbogenforellen (Oncorhynchus mykiss) und Äschen (Thymallus thymallus) keine Infektion bei Letzteren aus. Hechte konnten in diesen Versuchen nicht infiziert werden. Über die Anheftung und die Penetration von Sporen der Malacosporea bei Kontakt mit dem Fischwirt sind nur wenige Details bekannt. Offensichtlich dringen die Sporoplasmen dieser Sporen in die Epithelien des Wirts mittels amöboider Bewegungen ein. Zudem deuten die ultrasturkturellen Untersuchungen darauf hin, dass die Kiemen die Haupteintrittspforte für diesen Parasiten sind. Die Variabilität der Empfänglichkeit von vier Regenbogenforellenstämme und Bachforellen gegenüber T. bryosalmonae wurde mittels quantitativer real-time PCR untersucht. Dabei erwiesen sich Bachforellen als empfänglicher als Regenbogenforellen. In der Anfangsphase des Experiments wiesen zwei der Regenbogenforellenstämme eine geringere Parasitenlast auf als alle anderen Gruppen, allerdings vermehrten sich bei diesen beiden Stämmen die Parasiten schneller, was am letzten Entnahmezeitpunkt letztlich zur Angleichung der relativen Infektionsrate bei allen Stämmen führte. Mittels Immunhistochemie konnten Stadien von T. bryosalmonae in histologischen Schnitten detektiert werden, jedoch war ihre Anzahl gering. Im Gegensatz zu T. bryosalmonae sind die Kenntnisse zu den Lebenszyklen von Buddenbrockia spp. unvollständig und alle bekannten Arten dieser Gattung sind lediglich als Stadien im Bryozoenwirt beschrieben. In der vorliegenden Arbeit konnten bisher unbekannte Infektionen in den Nieren von Karpfen (Cyprinus carpio) und Elritzen (Phoxinus phoxinus) nachgewiesen werden. Der Elritzenparasit konnte als Buddenbrockia plumatellae identifiziert werden, wohingegen es sich bei dem Karpfenparasiten höchst wahrscheinlich um eine unbeschriebene Art handelt. Die Kohabitation von im Labor gezüchteten Bryozoen mit infizierten Karpfen führte nicht zu einem offenen Ausbruch der Infektion. Die Ergebnisse der vorliegenden Arbeit haben in entscheidendem Maße die Kenntnisse über das Wirtsspektrum und die Lebenszyklen von verschiedenen, auch mutmaßlich neuen, Malacosporea-Arten erweitert. Ebenso ergaben sich Hinweise auf Resistenzunterschiede verschiedener Regenbogenforellenstämme gegenüber T. bryosalmonae. Untersuchungen zu Aspekten der Invasion von T. bryosalmonae in den Fisch trugen entscheidend zur weiteren Aufklärung der frühen Infektionsprozesse der Malacosporea bei.The class Malacosporea is the most enigmatic, and probably the basal group of the unique metazoan phylum Myxozoa. They are known to parasitize fish and freshwater bryozoans, but still, most malacosporeans were only described from the invertebrate host. A complete life-cycle is merely known for Tetracapsuloides bryosalmonae, the parasite causing proliferative kidney disease in salmonid fish. Knowledge about host range, transmission mechanisms and intraspecific differences in resistance against malacosporean pathogens remains scarce hitherto. Therefore, the aim of the present thesis was to investigate the biology and the life-cycles of some malacosporean parasites in more detail. Firstly, the necessary culture of freshwater bryozoans to keep the life-cycle of these parasites in the laboratory could be established in the course of this study. Spores obtained from cultured bryozoans infected with malacosporeans thus enabled laboratory transmission experiments. It is well known that most salmonid species are susceptible to T. bryosalmonae-infection, but even in Northern pike (Esox lucius) developmental stages similar to this parasite were described previously. Nevertheless, transmission of this parasite to bryozoans was only achieved with infected brown trout (Salmo trutta). To find out whether other teleosts besides brown trout may also be suitable hosts for T. bryosalmonae, infection experiments with different fish species were conducted in the present study. By cohabitation of T. bryosalmonae-infected fish and laboratory raised bryozoans it was demonstrated that also brook trout (Salvelinus fontinalis) transmitted the disease to bryozoans. In contrast, infected rainbow trout (Oncorhynchus mykiss) and grayling (Thymallus thymallus) did not cause infection of the latter. Peculiarly, pike did not become infected at all in this experiment. For infection of such a wide range of fish species, a general mode of host invasion is necessary. Virtually no details about attachment and penetration of malacosporean spores encountering the fish host were known. To characterize these life-cycle stages ultra-structurally, infection trials and in vitro experiments with T. bryosalmonae actinospores were conducted. In vitro activation experiments, light microscopy and scanning electron microscopy (SEM) showed that sporoplasms of these spores penetrate host epithelia by means of amoeboid movement. Additionally, ultrastructural examinations indicated that the gills are main entry site for this parasite. Upon contact, the spores seemed to impair the gill epithelium to allow the entry of the sporoplasm at these sites. After penetration, the parasite is exposed to the immune system of the host, so the number of stages that enter and the intensity of the host response against the parasite will influence its development and multiplication. This variability in susceptibility was addressed in the present study, as reliable data about intra-specific differences in the response of fish to malacosporean infections was lacking up to this point. Four rainbow trout strains and brown trout were infected with T. bryosalmonae and infection intensity was monitored. According to results from quantitative real-time-PCR analysis, brown trout were more susceptible than rainbow trout. Two rainbow trout strains showed lower relative parasite load than all other groups early during the experiment, but parasites multiplied faster in these strains, resulting in an equal level of relative infection rate for all strains upon final sampling. T. bryosalmonae-stages were found stained by immuno-histochemistry in histological sections although their number was low, unfortunately impeding quantitative evaluation of parasite load. In contrast to T. bryosalmonae, knowledge of life-cycles of Buddenbrockia spp. was incomplete and all known species of this genus were described as stages in bryozoan hosts. In this study, cohabitation challenges with bryozoans containing the peculiar worm-like malaco-sporean stages and fish resulted in novel infections detected in kidneys of common carp (Cyprinus carpio) and minnow (Phoxinus phoxinus). Sequence comparison of 18S rDNA identified the parasite in minnows as Buddenbrockia plumatellae, while the carp infecting malacosporean is very likely a new species. Light and electron-microscopy of kidney samples of infected minnows and carp revealed parasite stages in the kidney tubules. Only single parasite cells were observed in minnow, while in carp, multicellular sporogonic stages were found in sections of kidney tubules. Cohabitation of laboratory raised bryozoans with infected carp did not yield in overt infection. Therefore, the complete life-cycle of this parasite has yet to be established. Phylogenetic analysis of the Buddenbrockia spp. known to date sub-stantiated the split of the B. plumatellae-clade into two lineages, but could not fully clarify the placement of the carp-infecting malacosporean. The results of this thesis fundamentally increased the knowledge on the range of compatible hosts and life-cycles of different, even putatively new, malacosporean species. Also, indi-cations for differential resistance of rainbow trout strains to T. bryosalmonae were found. Investigations on aspects of invasion of fish by T. bryosalmonae spores further clarified the early infection process of malacosporeans

Meta-Tracker: Fast and Robust Online Adaptation for Visual Object Trackers

This paper improves state-of-the-art visual object trackers that use online adaptation. Our core contribution is an offline meta-learning-based method to adjust the initial deep networks used in online adaptation-based tracking. The meta learning is driven by the goal of deep networks that can quickly be adapted to robustly model a particular target in future frames. Ideally the resulting models focus on features that are useful for future frames, and avoid overfitting to background clutter, small parts of the target, or noise. By enforcing a small number of update iterations during meta-learning, the resulting networks train significantly faster. We demonstrate this approach on top of the high performance tracking approaches: tracking-by-detection based MDNet and the correlation based CREST. Experimental results on standard benchmarks, OTB2015 and VOT2016, show that our meta-learned versions of both trackers improve speed, accuracy, and robustness.Comment: Code: https://github.com/silverbottlep/meta_tracker

Neurocognitive Effects of Transcranial Direct Current Stimulation in Arithmetic Learning and Performance: A Simultaneous tDCS-fMRI Study

BACKGROUND: A small but increasing number of studies suggest that non-invasive brain stimulation by means of transcranial direct current stimulation (tDCS) can modulate arithmetic processes that are essential for higher-order mathematical skills and that are impaired in dyscalculic individuals. However, little is known about the neural mechanisms underlying such stimulation effects, and whether they are specific to cognitive processes involved in different arithmetic tasks. METHODS: We addressed these questions by applying tDCS during simultaneous functional magnetic resonance imaging (fMRI) while participants were solving two types of complex subtraction problems: repeated problems, relying on arithmetic fact learning and problem-solving by fact retrieval, and novel problems, requiring calculation procedures. Twenty participants receiving left parietal anodal plus right frontal cathodal stimulation were compared with 20 participants in a sham condition. RESULTS: We found a strong cognitive and neural dissociation between repeated and novel problems. Repeated problems were solved more accurately and elicited increased activity in the bilateral angular gyri and medial plus lateral prefrontal cortices. Solving novel problems, in contrast, was accompanied by stronger activation in the bilateral intraparietal sulci and the dorsomedial prefrontal cortex. Most importantly, tDCS decreased the activation of the right inferior frontal cortex while solving novel (compared to repeated) problems, suggesting that the cathodal stimulation rendered this region unable to respond to the task-specific cognitive demand. CONCLUSIONS: The present study revealed that tDCS during arithmetic problem-solving can modulate the neural activity in proximity to the electrodes specifically when the current demands lead to an engagement of this area

Global first-passage times of fractal lattices

The global first passage time density of a network is the probability that a random walker released at a random site arrives at an absorbing trap at time T. We find simple expressions for the mean global first passage time for five fractals: the d-dimensional Sierpinski gasket, T fractal, hierarchical percolation model, Mandelbrot-Given curve, and a deterministic tree. We also find an exact expression for the second moment and show that the variance of the first passage time, Var(T), scales with the number of nodes within the fractal N such that Var(T)similar to N(4/d), where d is the spectral dimension