Vitamin, mineral and iron supplementation in pregnancy: cross-sectional study

Aim. To assess the use of vitamin, mineral and iron supplements during pregnancy in Zagreb and Novi Sad. Methods. The study was conducted by use of a structured standardized questionnaire consisting of two parts, i. e. data obtained by maternal interview and hospital records. It is designed as a cross-sectional study in two countries (Croatia and Serbia). The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. Results. In Zagreb, pregnant women reported highest utilization of vitamin-mineral supplements (n = 508; 56.9 %), whereas in Novi Sad these supplements ranked third (n = 408; 20.3 %), following tocolytics and iron supplements. There was no statistically significant difference in the prevalence of congenital malformations between neonates at in utero exposure to vitamins, minerals and iron supplements and those without such exposure in either Zagreb or Novi Sad arm, with the exception of iron and calcium supplementation in the Zagreb arm. Conclusions. In spite of certain study limitations, the results obtained pointed to the unreasonable and potentially harmful use of these supplements in pregnant women from Zagreb

Diffusion of particles moving with constant speed

The propagation of light in a scattering medium is described as the motion of a special kind of a Brownian particle on which the fluctuating forces act only perpendicular to its velocity. This enforces strictly and dynamically the constraint of constant speed of the photon in the medium. A Fokker-Planck equation is derived for the probability distribution in the phase space assuming the transverse fluctuating force to be a white noise. Analytic expressions for the moments of the displacement $$ along with an approximate expression for the marginal probability distribution function $P(x,t)$ are obtained. Exact numerical solutions for the phase space probability distribution for various geometries are presented. The results show that the velocity distribution randomizes in a time of about eight times the mean free time ($8t^*$) only after which the diffusion approximation becomes valid. This factor of eight is a well known experimental fact. A persistence exponent of $0.435 \pm 0.005$ is calculated for this process in two dimensions by studying the survival probability of the particle in a semi-infinite medium. The case of a stochastic amplifying medium is also discussed.Comment: 9 pages, 9 figures(Submitted to Phys. Rev. E

Solar flare prediction using advanced feature extraction, machine learning and feature selection

YesNovel machine-learning and feature-selection algorithms have been developed to study: (i) the flare prediction capability of magnetic feature (MF) properties generated by the recently developed Solar Monitor Active Region Tracker (SMART); (ii) SMART's MF properties that are most significantly related to flare occurrence. Spatio-temporal association algorithms are developed to associate MFs with flares from April 1996 to December 2010 in order to differentiate flaring and non-flaring MFs and enable the application of machine learning and feature selection algorithms. A machine-learning algorithm is applied to the associated datasets to determine the flare prediction capability of all 21 SMART MF properties. The prediction performance is assessed using standard forecast verification measures and compared with the prediction measures of one of the industry's standard technologies for flare prediction that is also based on machine learning - Automated Solar Activity Prediction (ASAP). The comparison shows that the combination of SMART MFs with machine learning has the potential to achieve more accurate flare prediction than ASAP. Feature selection algorithms are then applied to determine the MF properties that are most related to flare occurrence. It is found that a reduced set of 6 MF properties can achieve a similar degree of prediction accuracy as the full set of 21 SMART MF properties

Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A > G) in the essential UDP-glucose pyrophosphorylase (UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in UGP2 as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies

The inhibition of FGF receptor 1 activity mediates sorafenib-induced antiproliferative effects in human mesothelioma tumor-initiating cells

Tumor-initiating cells (TICs), the subset of cells within tumors endowed with stem-like features, being highly resistant to conventional cytotoxic drugs, are the major cause of tumor relapse. The identification of molecules able to target TICs remains a significant challenge in cancer therapy. Using TIC-enriched cultures (MM1, MM3 and MM4), from 3 human malignant pleural mesotheliomas (MPM), we tested the effects of sorafenib on cell survival and the intracellular mechanisms involved. Sorafenib inhibited cell-cycle progression in all the TIC cultures, but only in MM3 and MM4 cells this effect was associated with induction of apoptosis via the down-regulation of Mcl-1. Although sorafenib inhibits the activity of several tyrosine kinases, its effects are mainly ascribed to Raf inhibition. To investigate the mechanisms of sorafenib-mediated antiproliferative activity, TICs were treated with EGF or bFGF causing, in MM3 and MM4 cells, MEK, ERK1/2, Akt and STAT3 phosphorylation. These effects were significantly reduced by sorafenib in bFGF-treated cells, while a slight inhibition occurred after EGF stimulation, suggesting that sorafenib effects are mainly due to FGFR inhibition. Indeed, FGFR1 phosphorylation was inhibited by sorafenib. A different picture was observed in MM1 cells, which, releasing high levels of bFGF, showed an autocrine activation of FGFR1 and a constitutive phosphorylation/activation of MEK-ERK1/2. A powerful inhibitory response to sorafenib was observed in these cells, indirectly confirming the central role of sorafenib as FGFR inhibitor. These results suggest that bFGF signaling may impact antiproliferative response to sorafenib of MPM TICs, which is mainly mediated by a direct FGFR targeting

Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance

Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol–ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0–160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined

A New Technique for the Calculation and 3D Visualisation of Magnetic Complexities on Solar Satellite Images

YesIn this paper, we introduce two novel models for processing real-life satellite images to quantify and then visualise their magnetic structures in 3D. We believe this multidisciplinary work is a real convergence between image processing, 3D visualization and solar physics. The first model aims to calculate the value of the magnetic complexity in active regions and the solar disk. A series of experiments are carried out using this model and a relationship has been indentified between the calculated magnetic complexity values and solar flare events. The second model aims to visualise the calculated magnetic complexities in 3D colour maps in order to identify the locations of eruptive regions on the Sun. Both models demonstrate promising results and they can be potentially used in the fields of solar imaging, space weather and solar flare prediction and forecasting

A comparison of flare forecasting methods, I: results from the “All-clear” workshop

YesSolar flares produce radiation which can have an almost immediate effect on the near-Earth environ- ment, making it crucial to forecast flares in order to mitigate their negative effects. The number of published approaches to flare forecasting using photospheric magnetic field observations has prolifer- ated, with varying claims about how well each works. Because of the different analysis techniques and data sets used, it is essentially impossible to compare the results from the literature. This problem is exacerbated by the low event rates of large solar flares. The challenges of forecasting rare events have long been recognized in the meteorology community, but have yet to be fully acknowledged by the space weather community. During the interagency workshop on “all clear” forecasts held in Boulder, CO in 2009, the performance of a number of existing algorithms was compared on common data sets, specifically line-of-sight magnetic field and continuum intensity images from MDI, with consistent definitions of what constitutes an event. We demonstrate the importance of making such systematic comparisons, and of using standard verification statistics to determine what constitutes a good prediction scheme. When a comparison was made in this fashion, no one method clearly outperformed all others, which may in part be due to the strong correlations among the parameters used by different methods to characterize an active region. For M-class flares and above, the set of methods tends towards a weakly positive skill score (as measured with several distinct metrics), with no participating method proving substantially better than climatological forecasts.This work is the outcome of many collaborative and cooperative efforts. The 2009 “Forecasting the All-Clear” Workshop in Boulder, CO was sponsored by NASA/Johnson Space Flight Center’s Space Radiation Analysis Group, the National Center for Atmospheric Research, and the NOAA/Space Weather Prediction Center, with additional travel support for participating scientists from NASA LWS TRT NNH09CE72C to NWRA. The authors thank the participants of that workshop, in particular Drs. Neal Zapp, Dan Fry, Doug Biesecker, for the informative discussions during those three crazy days, and NCAR’s Susan Baltuch and NWRA’s Janet Biggs for organizational prowess. Workshop preparation and analysis support was provided for GB, KDL by NASA LWS TRT NNH09CE72C, and NASA Heliophysics GI NNH12CG10C. PAH and DSB received funding from the European Space Agency PRODEX Programme, while DSB and MKG also received funding from the European Union’s Horizon 2020 research and in- novation programme under grant agreement No. 640216 (FLARECAST project). MKG also acknowledges research performed under the A-EFFort project and subsequent service implementation, supported under ESA Contract number 4000111994/14/D/MPR. YY was supported by the National Science Foundation under grants ATM 09-36665, ATM 07-16950, ATM-0745744 and by NASA under grants NNX0-7AH78G, NNXO-8AQ90G. YY owes his deepest gratitude to his advisers Prof. Frank Y. Shih, Prof. Haimin Wang and Prof. Ju Jing for long discussions, for reading previous drafts of his work and providing many valuable comments that improved the presentation and contents of this work. JMA was supported by NSF Career Grant AGS-1255024 and by a NMSU Vice President for Research Interdisciplinary Research Grant