Introduction: Brachytherapy using permanently implantable collagen tiles containing cesium-131 (Cs-131) is indicated for treatment of malignant intracranial neoplasms. We quantified Cs-131 source ...migration and modeled the resulting dosimetric impact for Cs-131, iodine-125 (I-125), and palladium-103 (Pd-103). Methods and Materials: This was a retrospective analysis of a subgroup of patients enrolled in a prospective, single-center, nonrandomized, clinical trial (NCT03088579) of Cs-131 collagen tile brachytherapy. Postimplant Cs-131 plans and hypothetical I-125 and Pd-103 calculations were compared for 20 glioblastoma patients for a set seed geometry. Dosimetric impact of decay and seed migration was calculated for 2 hypothetical scenarios: Scenario 1, assuming seed positions on a given image set were unchanged until acquisition of the subsequent set; Scenario 2, assuming any change in seed positions occurred the day following acquisition of the prior images. Seed migration over time was quantified for a subset of 7 patients who underwent subsequent image-guided radiotherapy. Results: Mean seed migration was 1.7 mm (range: 0.7-3.1); maximum seed migration was 4.3 mm. Mean dose to the 60 Gy volume differed by 0.4 Gy (0.6%, range 0.1-1.0) and 0.9 Gy (1.5%, range 0.2-1.7) for Cs-131, 1.2 Gy (2.0%, range 0.1-2.1) and 1.6 Gy (2.6%, range 1.2-2.6) for I-125, and 0.8 Gy (1.3%, range 0.2-1.5) and 1.4 Gy (2.3%, range 0.3-1.9) for Pd-103, for Scenarios 1 and 2, respectively, compared with the postimplant plan. For a set seed geometry mean implant dose was higher for Pd-103 (1.3 times) and I-125 (1.1 times) versus Cs-131. Dose fall-off was steepest for Pd-103: gradient index 1.88 versus 2.23 (I-125) and 2.40 (Cs-131). Conclusions: Dose differences due to source migration were relatively small, suggesting robust prevention of seed migration from Cs-131-containing collagen tiles. Intratarget heterogeneity was greater with Pd-103 and I-125 than Cs-131. Dose fall-off was fastest with Pd-103 followed by I-125 and then Cs-131.
The consequences of mastitis in terms of dairy cow behavior are relatively unknown. Future assessment of dairy cow welfare during mastitis will be facilitated by knowledge about the potential of ...mastitis to induce sickness behavior. Our aim was to examine behavior of dairy cows in the period from 2 d before (d −2 and −1) to 3 d (d 0, 1, and 2) after experimental intramammary challenge with Escherichia coli. Effects of experimentally induced mastitis on behavior were examined in 20 primiparous Danish Holstein-Friesian cows, all 3 to 6 wk after calving and kept in tie stalls. After evening milking on d 0, each cow received an intramammary infusion with 20 to 40 cfu of E. coli in 1 healthy front quarter. Paraclinical and bacteriological examinations were conducted to confirm infection. Half of the cows were subjected to liver and udder biopsies twice during the trial. Behavior was video-recorded on 5 consecutive days, d −2 to +2 after challenge when the cows were not disturbed by humans. The behavior of the animals was compared among all days. Infection with E. coli altered the behavior of the dairy cows. Time spent feeding was lower in the initial 24h after infection compared with that on the other days (16.6±1.1, 16.5±1.0, 13.2±1.2, 18.1±1.1, and 16.0±0.8% of time for d −2, −1, 0, 1, and 2, respectively). The duration of standing idle increased on d 0 compared with that on the control days and d 1 and 2 (29.4±2.6, 28.0±2.3, 39.1±2.6, 31.4±3.8, and 25.9±2.6% of time for d −2, −1, 0, 1 and 2, respectively). The frequency of self-grooming behavior per hour decreased in the initial 24h compared with that on d −2, −1, and 2 (4.1±0.8, 5.4±1.9, 3.2±0.6, 3.6±0.6, and 4.8±1.0 for d −2, −1, 0, 1, and 2, respectively). Likewise, duration of rumination and frequency of turning the head against the udder decreased in the first days after infection (rumination: 32.2±1.6, 34.8±1.8, 27.9±1.7, 30.0±2.6, and 34.8±1.7% of time; and frequency of turning head: 0.6±0.1, 0.6±0.1, 0.3±0.1, 0.3±0.1, and 0.6±0.1 per hour for d −2, −1, 0, 1 and 2, respectively). The cows subjected to biopsies showed an overall decreased lying time during the entire observation period (36.3±1.5 vs. 46.1±2.2% of time) but not directly related to the period after the biopsies. Dairy cows show classic signs of illness behavior in the hours after intramammary challenge with E. coli. This knowledge can be useful for the development of welfare assessment protocols, early disease detection, and for future work aimed at understanding the behavioral needs of dairy cows suffering from mastitis.
Background:
Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response ...to treatment between individuals may exist.
Objective:
To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA.
Methods:
Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses.
Results:
The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk.
Conclusions:
MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.
The aim of this paper is to investigate the organization of research in high-performing research groups in an age of increasing competition and pressure from outside and within higher-education ...institutions. To explore how researchers navigate such pressures and demands, the practice and perceptions of four high-performing research groups in Denmark and the Netherlands are examined, and the extent to which these groups can be understood as "communities of practice" or if they are displaying "team"-like characteristics is discussed. Previous studies have shown the benefits of communities of practice for organizational performance, and the present study demonstrates that the successful groups do indeed share many characteristics with such communities. A central argument of the paper is, however, also that incentive structures, inherent in many new policy initiatives that are meant to foster excellence in science, are more directed at "team-like" organization by focusing on, e.g., formally organized work processes, predefined goals, milestones, work packages, and hierarchically organized consortia. The potential implications of this are discussed. (HRK / Abstract übernommen).
Summary
Although the movement of invasive bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) in the Upper Mississippi River system is dependent on their ability to swim through ...its numerous lock‐and‐dams, the swimming performance of adults of these species is at present unknown. Using a large (2,935‐L) mobile swim tunnel, the swimming performance of adult bighead and adult silver carp was quantified at water velocities that challenged them to exhibit either prolonged and/or burst swimming (76–244 cm/s) with fatigue times of less than 10 min. Simple log‐linear models best described the relative swim speed to fatigue relationships for both species. Under these conditions, the swimming performances of adult bighead and silver carp were similar to several species of adult fishes native to the Mississippi River system, but relatively low (<3 total body lengths per second, TL/s) compared to previously studied juveniles and sub‐adult bigheaded carps (3–15 TL/s). The decline in endurance with water velocity was three times greater in bighead carp (slope = −2.98) than in silver carp (slope = −1.01) and the predictive ability of the bighead model was appreciably better than the silver carp model. The differences in adult swimming performance between the two species were coincident with behavioral differences (e.g. breaching in silver carp but not in bighead carp). The swimming performance data of adult bighead and silver carp can now be used to evaluate whether their passage through manmade river structures including the gates of lock‐and‐dams in the Upper Mississippi River might be reduced.
This work presents a method to simulate the electromagnetic properties of superconductors with high aspect ratio such as the commercially available second generation superconducting YBCO tapes. The ...method is based on a multiscale representation for both thickness and width of the superconducting domains. A couple of test cases were successfully simulated and further investigations were made by means of structured (mapped) meshes. Here, large aspect ratio elements were used to simulate thin material layers with a reduced number of elements. Hence, more complex geometries can be studied at considerable lower computational time. Several test cases were simulated including transport current, externally applied magnetic field and a combination of both. The results are in good agreement with recently published numerical simulations. The computational time to solve the present multiscale approach in 2D is estimated as two orders of magnitude faster than other 2D methods.
Power Fluctuations From Large Wind Farms Sorensen, P.; Cutululis, N.A.; Vigueras-Rodriguez, A. ...
IEEE transactions on power systems,
08/2007, Volume:
22, Issue:
3
Journal Article
Peer reviewed
This paper deals with power fluctuations from wind farms. The time range in focus is between one minute and up to a couple of hours. In this time range, substantial power fluctuations have been ...observed during unstable weather conditions. A wind power fluctuation model is described, and measured time series from the first large offshore wind farm, Horns Rev in Denmark, are compared to simulated time series. The comparison between measured and simulated time series focuses on the ramping characteristics of the wind farm at different power levels and on the need for system generation reserves due to the fluctuations. The comparison shows a reasonable agreement between simulations and measurements, although there is still room for improvement of the simulation model.
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an ...AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism. The fourth variant in the SYTANLAAF motif most likely results in reduced permeability. The variant in the extracellular domain potentially interferes with the binding between the monomers. On the basis of clinical information and genetic results, and the fact that other subunits of the AMPA receptor have already been associated with neurodevelopmental disorders, we suggest that pathogenic de novo variants in GRIA4 lead to intellectual disability with or without seizures, gait abnormalities, problems of social behavior, and other variable features.
Summary
A commonly used procedure in genome‐wide association (GWA), genome‐wide expression (GWE) and expression quantitative trait locus (eQTL) analyses is based on a bottom‐up experimental approach ...that attempts to individually associate molecular variants with complex traits. Top‐down modeling of the entire set of genomic data and partitioning of the overall variance into subcomponents may provide further insight into the genetic basis of complex traits. To test this approach, we performed a whole‐genome variance components analysis and partitioned the genomic variance using information from GWA, GWE and eQTL analyses of growth‐related traits in a mouse F2 population. We characterized the mouse trait genetic architecture by ordering single nucleotide polymorphisms (SNPs) based on their P‐values and studying the areas under the curve (AUCs). The observed traits were found to have a genomic variance profile that differed significantly from that expected of a trait under an infinitesimal model. This situation was particularly true for both body weight and body fat, for which the AUCs were much higher compared with that of glucose. In addition, SNPs with a high degree of trait‐specific regulatory potential (SNPs associated with subset of transcripts that significantly associated with a specific trait) explained a larger proportion of the genomic variance than did SNPs with high overall regulatory potential (SNPs associated with transcripts using traditional eQTL analysis). We introduced AUC measures of genomic variance profiles that can be used to quantify relative importance of SNPs as well as degree of deviation of a trait's inheritance from an infinitesimal model. The shape of the curve aids global understanding of traits: The steeper the left‐hand side of the curve, the fewer the number of SNPs controlling most of the phenotypic variance.
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