Agglomeration behaviour of titanium dioxide nanoparticles in river waters: A multi-method approach combining light scattering and field-flow fractionation techniques

© 2015 Elsevier Ltd. Titanium dioxide nanoparticles (TiO2 NPs) are currently one of the most prolifically used nanomaterials, resulting in an increasing likelihood of release to the environment. This is of concern as the potential toxicity of TiO2 NPs has been investigated in several recent studies. Research into their fate and behaviour once entering the environment is urgently needed to support risk assessment and policy development. In this study, we used a multi-method approach combining light scattering and field-flow fractionation techniques to assess both the aggregation behaviour and aggregate structure of TiO2 NPs in different river waters. Results showed that both the aggregate size and surface-adsorbed dissolved organic matter (DOM) were strongly related to the initial DOM concentration of the tested waters (i.e. R2>0.90) suggesting that aggregation of TiO2 NPs is controlled by the presence and concentration of DOM. The conformation of the formed aggregates was also found to be strongly related to the surface-adsorbed DOM (i.e. R2>0.95) with increasing surface-adsorbed DOM leading to more compact structures. Finally, the concentration of TiO2 NPs remaining in the supernatant after sedimentation of the larger aggregates was found to decrease proportionally with both increasing IS and decreasing DOM concentration, resulting in more than 95% sedimentation in the highest IS sample

Assessing the aggregation behaviour of iron oxide nanoparticles under relevant environmental conditions using a multi-method approach

Iron nanoparticles are becoming increasingly popular for the treatment of contaminated soil and groundwater; however, their mobility and reactivity in subsurface environments are significantly affected by their tendency to aggregate. Assessing their stability under environmental conditions is crucial for determining their environmental fate. A multi-method approach (including different size-measurement techniques and the DLVO theory) was used to thoroughly characterise the behaviour of iron oxide nanoparticles (Fe2O3NPs) under environmentally relevant conditions. Although recent studies have demonstrated the importance of using a multi-method approach when characterising nanoparticles, the majority of current studies continue to use a single-method approach.Under some soil conditions (i.e. pH 7, 10mM NaCl and 2mM CaCl2) and increasing particle concentration, Fe2O3NPs underwent extensive aggregation to form large aggregates (>1μm). Coating the nanoparticles with dissolved organic matter (DOM) was investigated as an alternative "green" solution to overcoming the aggregation issue instead of using the more commonly proposed polyelectrolytes. At high concentrations, DOM effectively covered the surface of the Fe2O3NPs, thereby conferring negative surface charge on the particles across a wide range of pH values. This provided electrostatic stabilisation and considerably reduced the particle aggregation effect. DOM-coated Fe2O3NPs also proved to be more stable under high ionic strength conditions. The presence of CaCl2, however, even at low concentrations, induced the aggregation of DOM-coated Fe2O3NPs, mainly via charge neutralisation and bridging. This has significant implications in regards to the reactivity and fate of these materials in the environment. © 2013 Elsevier Ltd

Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma.

Mice in which lung epithelial cells can be induced to express an oncogenic Kras(G12D) develop lung adenocarcinomas in a manner analogous to humans. A myriad of genetic changes accompany lung adenocarcinomas, many of which are poorly understood. To get a comprehensive understanding of both the transcriptional and post-transcriptional changes that accompany lung adenocarcinomas, we took an omics approach in profiling both the coding genes and the non-coding small RNAs in an induced mouse model of lung adenocarcinoma. RNAseq transcriptome analysis of Kras(G12D) tumors from F1 hybrid mice revealed features specific to tumor samples. This includes the repression of a network of GTPase-related genes (Prkg1, Gnao1 and Rgs9) in tumor samples and an enrichment of Apobec1-mediated cytosine to uridine RNA editing. Furthermore, analysis of known single-nucleotide polymorphisms revealed not only a change in expression of Cd22 but also that its expression became allele specific in tumors. The most salient finding, however, came from small RNA sequencing of the tumor samples, which revealed that a cluster of ∼53 microRNAs and mRNAs at the Dlk1-Dio3 locus on mouse chromosome 12qF1 was markedly and consistently increased in tumors. Activation of this locus occurred specifically in sorted tumor-originating cancer cells. Interestingly, the 12qF1 RNAs were repressed in cultured Kras(G12D) tumor cells but reactivated when transplanted in vivo. These microRNAs have been implicated in stem cell pleuripotency and proteins targeted by these microRNAs are involved in key pathways in cancer as well as embryogenesis. Taken together, our results strongly imply that these microRNAs represent key targets in unraveling the mechanism of lung oncogenesis

European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

© American Association of Pharmaceutical Scientists 2016, published by Springer US, available online at doi: https://doi.org/10.1208/s12249-016-0584-1The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.Peer reviewedFinal Accepted Versio

Injury epidemiology after the 2001 Gujarat earthquake in India: a retrospective analysis of injuries treated at a rural hospital in the Kutch district immediately after the disaster

The number of injured far exceeds those dead and the average injury to mortality ratio in earthquakes stands at 3:1. Immediate effective medical response significantly influences injury outcomes and thus the overall health impact of earthquakes. Inadequate or mismanagement of injuries may lead to disabilities. The lack of precise data from immediate aftermath is seen as a remarkable weak point in disaster epidemiology and warrants evidence generation.To analyze the epidemiology of injuries and the treatment imparted at a secondary rural hospital in the Kutch district, Gujarat, India following the January 26, 2001 earthquake.Discharge reports of patients admitted to the hospital over 10 weeks were analyzed retrospectively for earthquake-related injuries.Orthopedic injuries, (particularly fractures of the lower limbs) were predominant and serious injuries like head, chest, abdominal, and crush syndrome were minimal. Wound infections were reported in almost 20% of the admitted cases. Surgical procedures were more common than conservative treatment. The most frequently performed surgical procedures were open reduction with internal fixation and cleaning and debridement of contaminated wounds. Four secondary deaths and 102 transfers to tertiary care due to complications were reported.The injury epidemiology reported in this study is in general agreement with most other studies reporting injury epidemiology except higher incidence of distal orthopedic injuries particularly to the lower extremities. We also found that young males were more prone to sustaining injuries. These results warrant further research. Inconsistent data reporting procedures against the backdrop of inherent disaster data incompleteness calls for urgent standardization of reporting earthquake injuries for evidence-based response policy planning

Topical Polyethylene Glycol as a Novel Chemopreventive Agent for Oral Cancer via Targeting of Epidermal Growth Factor Response

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG) has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide) rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall) post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat) without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis

Evaluation of Errors Associated with Cutting-Induced Plasticity in Residual Stress Measurements Using the Contour Method

Cutting-induced plasticity can lead to elevated uncertainties in residual stress measurements made by the contour method. In this study plasticity-induced stress errors are numerically evaluated for a benchmark edge-welded beam to understand the underlying mechanism. Welding and cutting are sequentially simulated by finite element models which have been validated by previous experimental results. It is found that a cutting direction normal to the symmetry plane of the residual stress distribution can lead to a substantially asymmetrical back-calculated stress distribution, owing to cutting-induced plasticity. In general, the stresses at sample edges are most susceptible to error, particularly when the sample is restrained during cutting. Inadequate clamping (far from the plane of cut) can lead to highly concentrated plastic deformation in local regions, and consequently the back-calculated stresses have exceptionally high values and gradients at these locations. Furthermore, the overall stress distribution is skewed towards the end-of-cut side. Adequate clamping (close to the plane of cut) minimises errors in back-calculated stress which becomes insensitive to the cutting direction. For minimal constraint (i.e. solely preventing rigid body motion), the plastic deformation is relatively smoothly distributed, and an optimal cutting direction (i.e. cutting from the base material towards the weld region in a direction that falls within the residual stress symmetry plane) is identified by evaluating the magnitude of stress errors. These findings suggest that cutting process information is important for the evaluation of potential plasticity-induced errors in contour method results, and that the cutting direction and clamping strategy can be optimised with an understanding of their effects on plasticity and hence the back-calculated stresses

Bounds on 4D Conformal and Superconformal Field Theories

We derive general bounds on operator dimensions, central charges, and OPE coefficients in 4D conformal and N=1 superconformal field theories. In any CFT containing a scalar primary phi of dimension d we show that crossing symmetry of implies a completely general lower bound on the central charge c >= f_c(d). Similarly, in CFTs containing a complex scalar charged under global symmetries, we bound a combination of symmetry current two-point function coefficients tau^{IJ} and flavor charges. We extend these bounds to N=1 superconformal theories by deriving the superconformal block expansions for four-point functions of a chiral superfield Phi and its conjugate. In this case we derive bounds on the OPE coefficients of scalar operators appearing in the Phi x Phi* OPE, and show that there is an upper bound on the dimension of Phi* Phi when dim(Phi) is close to 1. We also present even more stringent bounds on c and tau^{IJ}. In supersymmetric gauge theories believed to flow to superconformal fixed points one can use anomaly matching to explicitly check whether these bounds are satisfied.Comment: 47 pages, 9 figures; V2: small corrections and clarification

Phenomenology of Light Sneutrino Dark Matter in cMSSM/mSUGRA with Inverse Seesaw

We study the possibility of a light Dark Matter (DM) within a constrained Minimal Supersymmetric Standard Model (cMSSM) framework augmented by a SM singlet-pair sector to account for the non-zero neutrino masses by inverse seesaw mechanism. Working within a 'hybrid' scenario with the MSSM sector fixed at high scale and the singlet neutrino sector at low scale, we find that, contrary to the case of the usual cMSSM where the neutralino DM cannot be very light, we can have a light sneutrino DM with mass below 100 GeV satisfying all the current experimental constraints from cosmology, collider as well as low-energy experiments. We also note that the supersymmetric inverse seesaw mechanism with sneutrino as the lightest supersymmetric partner can have enhanced same-sign dilepton final states with large missing transverse energy (mET) coming from the gluino- and squark-pair as well as the squark-gluino associated productions and their cascade decay through charginos. We present a collider study for the same-sign dilepton+jets+mET signal in this scenario and propose some distinctions with the usual cMSSM. We also comment on the implications of such a light DM scenario on the invisible decay width of an 125 GeV Higgs boson.Comment: 24 pages, 4 figures, 7 tables; matches published versio