We report the results of a 28-day oral exposure study in rats, exposed to <20 nm noncoated, or <15 nm PVP-coated silver nanoparticles (Ag = 90 mg/kg body weight (bw)), or AgNO3 (Ag = 9 mg/kg bw), or ...carrier solution only. Dissection was performed at day 29, and after a wash-out period of 1 or 8 weeks. Silver was present in all examined organs with the highest levels in the liver and spleen for all silver treatments. Silver concentrations in the organs were highly correlated to the amount of Ag+ in the silver nanoparticle suspension, indicating that mainly Ag+, and to a much lesser extent silver nanoparticles, passed the intestines in the silver nanoparticle exposed rats. In all groups silver was cleared from most organs after 8 weeks postdosing, but remarkably not from the brain and testis. Using single particle inductively coupled plasma mass spectrometry, silver nanoparticles were detected in silver nanoparticle exposed rats, but, remarkably also in AgNO3 exposed rats, hereby demonstrating the formation of nanoparticles from Ag+ in vivo that are probably composed of silver salts. Biochemical markers and antibody levels in blood, lymphocyte proliferation and cytokine release, and NK-cell activity did not reveal hepatotoxicity or immunotoxicity of the silver exposure. In conclusion, oral exposure to silver nanoparticles appears to be very similar to exposure to silver salts. However, the consequences of in vivo formation of silver nanoparticles, and of the long retention of silver in brain and testis should be considered in a risk assessment of silver nanoparticles.
We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened ...controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻⁷), SP4 (P=7.68 x 10⁻⁷) and GRM7 (P=1.11 x 10⁻⁶). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.
Titanium dioxide (TiO
) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO
to accumulate in human liver and ...spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO
particle consumption could not be excluded then.
Here we show the first quantification of both total titanium (Ti) and TiO
particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO
particles. The presence of TiO
in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry.
These results prove that TiO
particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO
cannot be excluded.
We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer ...patients.
Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy.
Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy.
Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.
The Very Large Array Sky Survey (VLASS) is a synoptic, all-sky radio sky survey with a unique combination of high angular resolution ( 2 5), sensitivity (a 1 goal of 70 Jy/beam in the coadded data), ...full linear Stokes polarimetry, time domain coverage, and wide bandwidth (2-4 GHz). The first observations began in 2017 September, and observing for the survey will finish in 2024. VLASS will use approximately 5500 hr of time on the Karl G. Jansky Very Large Array (VLA) to cover the whole sky visible to the VLA (decl. > −40°), a total of 33 885 deg 2 . The data will be taken in three epochs to allow the discovery of variable and transient radio sources. The survey is designed to engage radio astronomy experts, multi-wavelength astronomers, and citizen scientists alike. By utilizing an "on the fly" interferometry mode, the observing overheads are much reduced compared to a conventional pointed survey. In this paper, we present the science case and observational strategy for the survey, and also results from early survey observations.
The Plumbing of Land Surface Models Best, M. J.; Abramowitz, G.; Johnson, H. R. ...
Journal of hydrometeorology,
06/2015, Letnik:
16, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The Protocol for the Analysis of Land Surface Models (PALS) Land Surface Model Benchmarking Evaluation Project (PLUMBER) was designed to be a land surface model (LSM) benchmarking intercomparison. ...Unlike the traditional methods of LSM evaluation or comparison, benchmarking uses a fundamentally different approach in that it sets expectations of performance in a range of metrics a priori—before model simulations are performed. This can lead to very different conclusions about LSM performance. For this study, both simple physically basedmodels and empirical relationships were used as the benchmarks. Simulations were performed with 13 LSMs using atmospheric forcing for 20 sites, and then model performance relative to these benchmarks was examined. Results show that even for commonly used statistical metrics, the LSMs’ performance varies considerably when compared to the different benchmarks. All models outperform the simple physically based benchmarks, but for sensible heat flux the LSMs are themselves outperformed by an out-of-sample linear regression against downward shortwave radiation. While moisture information is clearly central to latent heat flux prediction, the LSMs are still outperformed by a three-variable nonlinear regression that uses instantaneous atmospheric humidity and temperature in addition to downward shortwave radiation. These results highlight the limitations of the prevailing paradigm of LSM evaluation that simply compares an LSM to observations and to other LSMs without a mechanism to objectively quantify the expectations of performance. The authors conclude that their results challenge the conceptual view of energy partitioning at the land surface.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Synthetic Amorphous Silica (SAS) is commonly used in food and drugs. Recently, a consumer intake of silica from food was estimated at 9.4 mg/kg bw/day, of which 1.8 mg/kg bw/day was estimated to be ...in the nano-size range. Food products containing SAS have been shown to contain silica in the nanometer size range (i.e. 5-200 nm) up to 43% of the total silica content. Concerns have been raised about the possible adverse effects of chronic exposure to nanostructured silica.
Rats were orally exposed to 100, 1000 or 2500 mg/kg bw/day of SAS, or to 100, 500 or 1000 mg/kg bw/day of NM-202 (a representative nanostructured silica for OECD testing) for 28 days, or to the highest dose of SAS or NM-202 for 84 days.
SAS and NM-202 were extensively characterized as pristine materials, but also in the feed matrix and gut content of the animals, and after in vitro digestion. The latter indicated that the intestinal content of the mid/high-dose groups had stronger gel-like properties than the low-dose groups, implying low gelation and high bioaccessibility of silica in the human intestine at realistic consumer exposure levels. Exposure to SAS or NM-202 did not result in clearly elevated tissue silica levels after 28-days of exposure. However, after 84-days of exposure to SAS, but not to NM-202, silica accumulated in the spleen. Biochemical and immunological markers in blood and isolated cells did not indicate toxicity, but histopathological analysis, showed an increased incidence of liver fibrosis after 84-days of exposure, which only reached significance in the NM-202 treated animals. This observation was accompanied by a moderate, but significant increase in the expression of fibrosis-related genes in liver samples.
Although only few adverse effects were observed, additional studies are warranted to further evaluate the biological relevance of observed fibrosis in liver and possible accumulation of silica in the spleen in the NM-202 and SAS exposed animals respectively. In these studies, dose-effect relations should be studied at lower dosages, more representative of the current exposure of consumers, since only the highest dosages were used for the present 84-day exposure study.
Abstract Introduction The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic ...breast cancer compared with the cost-effectiveness based on the efficacy results from a trial. Methods A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted. Results In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained. Conclusion According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario.
A person's emotions and state of mind are apparent in their face and eyes. As a Latin proverb states: ‘The face is the portrait of the mind; the eyes, its informers’. This presents a significant ...challenge for Computer Graphics researchers who generate artificial entities that aim to replicate the movement and appearance of the human eye, which is so important in human–human interactions. This review article provides an overview of the efforts made on tackling this demanding task. As with many topics in computer graphics, a cross‐disciplinary approach is required to fully understand the workings of the eye in the transmission of information to the user. We begin with a discussion of the movement of the eyeballs, eyelids and the head from a physiological perspective and how these movements can be modelled, rendered and animated in computer graphics applications. Furthermore, we present recent research from psychology and sociology that seeks to understand higher level behaviours, such as attention and eye gaze, during the expression of emotion or during conversation. We discuss how these findings are synthesized in computer graphics and can be utilized in the domains of Human–Robot Interaction and Human–Computer Interaction for allowing humans to interact with virtual agents and other artificial entities. We conclude with a summary of guidelines for animating the eye and head from the perspective of a character animator.
A person's emotions and state of mind are apparent in their face and eyes. As a Latin proverb states: ‘The face is the portrait of the mind; the eyes, its informers’. This presents a significant challenge for Computer Graphics researchers who generate artificial entities that aim to replicate the movement and appearance of the human eye, which is so important in human–human interactions. This review article provides an overview of the efforts made on tackling this demanding task. As with many topics in computer graphics, a cross‐disciplinary approach is required to fully understand the workings of the eye in the transmission of information to the user.
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