Probing plasma fluorinated graphene via spectromicroscopy.

Plasma fluorination of graphene is studied using a combination of spectroscopy and microscopy techniques, giving insight into the yield and fluorination mechanism for functionalization of supported graphene with both CF4 and SF6 gas precursors. Ion acceleration during fluorination is used to probe the effect on grafting functionalities. Adatom clustering, which occurs with CF4 plasma treatment, is suppressed when higher kinetic energy is supplied to the ions. During SF6 plasma functionalization, the sulfur atoms tend to bond to bare copper areas instead of affecting the graphene chemistry, except when the kinetic energy of the ions is restricted. Using scanning photoelectron microscopy, with a 100 nm spatial resolution, the chemical bonding environment is evaluated in the fluorinated carbon network at selected regions and the functionalization homogeneity is controlled in individual graphene flakes.

Pharmacogenomic information in drug labels: European Medicines Agency perspective.

Pharmacogenomics (PGx) has a growing impact on healthcare and constitutes one of the major pillars of personalised medicine. For the purpose of improved individualised drug treatment, there is an increasing effort to develop drugs suitable for specific subpopulations and to incorporate pharmacogenomic drug labels in existing and novel medicines. Here, we review the pharmacogenomic drug labels of all 517 medicinal products centrally approved in the European Union (EU) since the establishment of the European Medicines Agency in 1995. We identified all pharmacogenomic-related information mentioned in the product labels and classified it according to its main effect and function on drug treatment, that is, metabolism, transport and pharmacodynamics, and according to the place of the respective section of the Summary of Product Characteristics (SmPC). The labels are preferentially present in drugs having antineoplastic properties. We find that the number of drugs with pharmacogenomic labels in EU increases now steadily and that it will be an important task for the future to refine the legislation on how this information should be utilised for improvement of drug therapy.

Surface Effects on the Mott-Hubbard Transition in Archetypal V{2}O{3}.

We present an experimental and theoretical study exploring surface effects on the evolution of the metal-insulator transition in the model Mott-Hubbard compound Cr-doped V{2}O{3}. We find a microscopic domain formation that is clearly affected by the surface crystallographic orientation. Using scanning photoelectron microscopy and x-ray diffraction, we find that surface defects act as nucleation centers for the formation of domains at the temperature-induced isostructural transition and favor the formation of microscopic metallic regions. A density-functional theory plus dynamical mean-field theory study of different surface terminations shows that the surface reconstruction with excess vanadyl cations leads to doped, and hence more metallic, surface states, which explains our experimental observations.

Combining synchrotron radiation techniques for the analysis of gold coins from the Roman Empire.

Four gold coins minted in the V century have been studied with non-destructive synchrotron radiation techniques, namely X-Ray Fluorescence (XRF) and X-ray Absorption Near Edge Spectroscopy (XANES). XRF data analyzed coupling standard and statistical methods were used to distinguish the composition of the alloy constituting the coins from that of successive deposits processes. Our analysis presents a quantification of the trace elements present in the metallic alloy providing interesting details for historical insight. Furthermore, on the basis of the XRF maps, some regions of interest were selected for XANES at the K-edge of Fe. Our analysis of the Fe spectra points out two main phases which can be related to Fe oxides naturally present in soil. From the relative abundance of these oxides, information on the site where the coins were found can be obtained, providing additional information on their fate across the centuries.

The advanced therapy classification procedure. Overview of experience gained so far.

The classification procedure, introduced by the European Regulation on advanced therapy medicinal products (ATMPs), has received a tremendous interest from companies, academic and public sponsors developing ATMPs. This procedure gives companies the opportunity to verify whether or not the product they are developing can be considered an ATMP and can therefore benefit from the new regulatory pathway introduced in the European Union for these types of medicinal products. This procedure is optional, free of charge and may take place at any stage of the development of an ATMP in advance of applying for a marketing authorisation. In case of doubt, briefing meetings organised by the European Medicines Agency Innovation Task Force may help preparing for an ATMP classification and are a starting point for the interactions between the Agency and the developers of ATMPs. This article reviews the advantages of the classification procedure for both the developers of ATMPs and the European regulatory network. Since the introduction of this procedure and up to 10 November 2010, the Committee for Advanced Therapies (CAT) has finalised 38 applications for classification.

[Expression of thrombomodulin in malignant pleural mesothelioma]. / Espressione della trombomodulina nel mesotelioma maligno della pleura.

The malignant mesothelioma (MM) is often complicated by thromboembolic episodes, with thrombomodulin (TM) playing a role in the anti-coagulant process. We analyzed TM expression in biopsies of MM patients and in normal mesothelial tissue. The role of DNA methylation-associated gene silencing in TM expression was investigated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by their treatment with 5-aza-2'-deoxycytidine while the epigenetic agent did not affect TM expression in Met-5A cells. Methylation of the TM promoter is responsible for silencing of TM expression in MM tissue.

How the anisotropy of surface oxide formation influences the transient activity of a surface reaction.

Scanning photoelectron microscopy (SPEM) and photoemission electron microscopy (PEEM) allow local surface analysis and visualising ongoing reactions on a µm-scale. These two spatio-temporal imaging methods are applied to polycrystalline Rh, representing a library of well-defined high-Miller-index surface structures. The combination of these techniques enables revealing the anisotropy of surface oxidation, as well as its effect on catalytic hydrogen oxidation. In the present work we observe, using locally-resolved SPEM, structure-sensitive surface oxide formation, which is summarised in an oxidation map and quantitatively explained by the novel step density (SDP) and step edge (SEP) parameters. In situ PEEM imaging of ongoing H2 oxidation allows a direct comparison of the local reactivity of metallic and oxidised Rh surfaces for the very same different stepped surface structures, demonstrating the effect of Rh surface oxides. Employing the velocity of propagating reaction fronts as indicator of surface reactivity, we observe a high transient activity of Rh surface oxide in H2 oxidation. The corresponding velocity map reveals the structure-dependence of such activity, representing a direct imaging of a structure-activity relation for plenty of well-defined surface structures within one sample.

Coexisting multi-states in catalytic hydrogen oxidation on rhodium.

Catalytic hydrogen oxidation on a polycrystalline rhodium foil used as a surface structure library is studied by scanning photoelectron microscopy (SPEM) in the 10-6 mbar pressure range, yielding spatially resolved X-ray photoemission spectroscopy (XPS) measurements. Here we report an observation of a previously unknown coexistence of four different states on adjacent differently oriented domains of the same Rh sample at the exactly same conditions. A catalytically active steady state, a catalytically inactive steady state and multifrequential oscillating states are simultaneously observed. Our results thus demonstrate the general possibility of multi-states in a catalytic reaction. This highly unusual behaviour is explained on the basis of peculiarities of the formation and depletion of subsurface oxygen on differently structured Rh surfaces. The experimental findings are supported by mean-field micro-kinetic modelling. The present observations raise the interdisciplinary question of how self-organising dynamic processes in a heterogeneous system are influenced by the permeability of the borders confining the adjacent regions.

The Electron Affinity as the Highest Occupied Anion Orbital Energy with a Sufficiently Accurate Approximation of the Exact Kohn-Sham Potential.

Negative ions are not accurately represented in density functional approximations (DFAs) such as (semi)local density functionals (LDA or GGA or meta-GGA). This is caused by the much too high orbital energies (not negative enough) with these DFAs compared to the exact Kohn-Sham values. Negative ions very often have positive DFA HOMO energies, hence they are unstable. These problems do not occur with the exact Kohn-Sham potential, the anion HOMO energy then being equal to minus the electron affinity. It is therefore desirable to develop sufficiently accurate approximations to the exact Kohn-Sham potential. There are further beneficial effects on the orbital shapes and the density of using a good approximation to the exact KS potential. Notably the unoccupied orbitals are not unduly diffuse, as they are in the Hartree-Fock model, with hybrid functionals, and even with (semi)local density functional approximations (LDFAs). We show that the recently developed B-GLLB-VWN approximation [Gritsenko et al. J. Chem. Phys. 2016, 144, 204114] to the exact KS potential affords stable negative ions with HOMO orbital energy close to minus the electron affinity.

Turning down the heat: An enhanced understanding of the relationship between urban vegetation and surface temperature at the city scale.

Guiding urban planners on the cooling returns of different configurations of urban vegetation is important to protect urban dwellers from adverse heat impacts. To this end, we estimated statistical models that fused multi-temporal very fine spatial (20 cm) and vertical (1 mm) resolution imagery, that captures the complexity of urban vegetation, with remotely sensed temperature data to assess how urban vegetation configuration influences urban temperatures. Perth, Western Australia, was used as a case-study for this analysis. Panel regression models showed that within a location an increase in tree and shrub cover has a larger cooling effect than grass coverage. On average, holding all else equal, an approximate 1 km2 increase in shrub (tree) cover within a location reduces surface temperatures by 12 °C (5 °C). We included a range of robustness checks for the observed relationships between urban vegetation type and temperature. Geographically weighted regression models showed spatial variation in the cooling effect of different vegetation types; this indicates that i) unobserved factors moderate temperature-vegetation relationships across urban landscapes, and ii) that urban vegetation type and temperature relationships are complex. Machine learning models (Random Forests) were used to further explore complex and non-linear relationships between different urban vegetation configurations and temperature. The Random Forests showed that vegetation type explained 31.84% of the out-of-bag variance in summer surface temperatures, that increased cover of large vegetation within a location increases cooling, and that different configurations of urban vegetation structure can lead to cooling gains. The models in this study were trained with vegetation data capturing local detail, multiple time-periods, and entire city coverage. Thus, these models illustrate the potential to develop locally-detailed and spatially explicit tools to guide planning of vegetation configuration to optimise cooling at local- and city-scales.

Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study.

BACKGROUND: Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). MATERIAL AND METHODS: Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. RESULTS: 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. CONCLUSION: Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT.

[Preventing measures facilitate the preservation of the levels of employment]. / Interventi prevenzionistici possono consentire di conservare i livelli occupazionali.

The implementation of the European Directive No 391/89, among the other news, introduced the obligation for the occupational physician to actively participate to the assessment of risks. The reduction of the incidence of "historical" professional pathologies and the arising of work-related disease is making the role of the occupational physician, in the survey and risk assessment, ever more important, especially in consideration of the physiological and biomechanical peculiar competences required. In addition, a correct risk assessment allows to optimise the valorisation of human resources. The occupational physician, in other terms, can not only protect the health of workers, but "save" jobs too. The survey carried out in a logistic unit of a large-scale distributors group, documented herein, can give evidence of that.

[Low back pain in VDT operators: importance of sports activities]. / Disturbi muscoloscheletrici lombari in addetti al VDT: influenza dell'attività sportiva svolta nel tempo libero.

Video display terminal (VDT) operators are required to maintain a sitting position for extended periods of time. This transverse study assessed the prevalence of lumbar musculoskeletal disorders (low back pain, LBP) in a population of VDT operators and related results to occupational factors and other interfering variables. Data were collected using questionnaires administered to 210 public employees. LBP was defined and evaluated using the Standardized Nordic Questionnaire. The prevalence of LBP was 58.4%; it correlated significantly with the female sex, spinal disorders, sleep disturbances and stress levels. There was a significant negative correlation with exercise and sports activities and with leisure time computer use. Multiple logistic regression adjusted for age and body mass index yielded an LBP odds ratio of 0.19 (C.I.95% 0.07-0.51) for sport-practicing subjects. At least one hour of exercise weekly was the cut-off for a significant reduction in LBP prevalence. The proportion of lumbar musculoskeletal symptoms was not significantly different in VDT operators and the general population. None of the occupational variables considered correlated with development of LBP. The occupational physician should recommend VDT operators to devote some leisure time to exercise.

[Biomarkers for prevention and early diagnosis of malignant pleural mesothelioma]. / Utilizzo di biomarkers nella prevenzione e diagnosi precoce del Mesotelioma Maligno della pleura.

Improved detection methods for diagnosis of asymptomatic malignant pleural mesothelioma (MPM) are essential for an early and reliable detection and treatment of this disease. Thus, focus has been on finding tumour markers in the blood. 94 asbestos-exposed subjects, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the significance of 8-hydroxy-2'-deoxy-guanosine (80HdG) in white blood cells and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors (PDGFbeta, HGF, bFGF, VEGFbeta), and matrix proteases (MMP2, MMP9, TIMP1, TIMP2) for potential early detection of MM. The area under ROC curves (AUC) indicates that 80HdG levels can discriminate asbestos-exposed subjects from controls but not from MPM patients. Significant AUC values were found for SMRP discriminating asbestos-exposed subjects from MPM patients but not from controls. VEGFbeta can significantly differentiate asbestos-exposed subjects from control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, TIMP2. The sensitivity and specificity results of markers were calculated at defined cut-offs. The combination of 80HdG, VEGFbeta and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MPM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

[Study of a population exposed to occupational stress: correlation among psychometrics tests and biochemical-immunological parameters]. / Studio di una popolazione esposta a stress occupazionale: correlazione tra tests psicometrici e parametri biochimico-immunologici.

A longitudinal study was carried out to evaluate the effect of psycho-physical and occupational stress on some biochemical and immunological parameters. The study was aimed to the identification of new and reliable method for the identification of subjects at high risk of occupational stress. 101 nurses which were working at several departments were enrolled. A blood sample was collected from all subjects after have filled the questionnaires at the time T0 and at the followed time points of 4 months (T1), 8 months (T2) and 12 months (T3). The self-reported questionnaires were: Rating Scale for Rapid Stress Assessment (VRS), General Health Questionnaire to 12 items (GHQ-12) Multidimensional Scale of Perceived Social Support (MSPSS) and a questionnaire on the occupational satisfaction (SOD). Haemachrome glycaemia, homocysteine, cortisol, lymphocyte numbers and their subtypes (CD4, CD8, CD19, NK CD56, NK CD57), NK activity and inflammatory cytokines were evaluated. A high reliability has been found between the psychometric tests. Correlations between biochemical and immunological variables were performed by Pearson coefficients and multiple regression analysis. Subjects with elevated value of stress evaluated as VRS and GHQ-12 score showed an altered immune response. A reduction of NK CD57 and IL-6 content better characterize the occupational satisfaction.

Nanocrystalline metal/carbon composites produced by supersonic cluster beam deposition.

In this work we show that supersonic cluster beam deposition is a viable method for the synthesis of nanocrystalline metal/carbon composites. By assembling carbon and metallic clusters seeded in a supersonic beam, we have grown films consisting of metal nanoparticles embedded in a nano-structured carbon matrix. Samples containing 3d transition metals (Ti, Ni) and noble metals (Au, Pd, Pt) with different metal abundances, particle size and dilution have been characterized by transmission electron microscopy. The influence of different metals on the structure of the carbon matrix has been investigated. Spatially resolved ultraviolet photoemission electron spectroscopy showed substantial surface oxidation of 3d transition metal clusters. On a micrometric scale, the spatial distribution of the metallic nanoparticles appeared to be homogeneous.

Decrease in peripheral blood polymorphonuclear leukocyte chemotactic index in endometriosis: role of prostaglandin E2 release.

OBJECTIVE: To investigate the effect of disease on peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cell cytotoxicity and to provide additional information concerning the cell-mediated immune function in endometriosis. METHODS: Chemotactic index of peripheral blood polymorphonuclear leukocytes, natural killer cell activity, and plasma estradiol (E2) and plasma prostaglandin (PG) E2 levels were evaluated in 46 women who underwent laparoscopy or laparotomy for pelvic pain, infertility, and/or benign adnexal masses. RESULTS: The 20 women (43%) with endometriosis showed a decrease in peripheral blood polymorphonuclear leukocyte chemotactic index, related to advanced disease stage (P < .001). A significant inverse correlation was observed between plasma PGE2 levels and chemotactic index in stage III and IV endometriosis (r = -.73, P = .004). Similarly, natural cytotoxicity was decreased significantly with respect to the stage of endometriosis (P = .004) and related inversely to plasma PGE2 levels (r = -.74, P = .003). A direct relationship was observed between PGE2 and plasma E2 levels (r = .59, P = .006). CONCLUSION: Advanced endometriosis is associated with decreased peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cytotoxicity, which may be related to plasma PGE2 and E2 levels.

Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway.

Wollastonite fibers were tested in vitro for their ability to produce reactive oxygen species (ROS) with two different systems: a cell-free reactive mixture containing deoxyribose and a polymorphonuclear leukocyte suspension. After adding the fibers, we measured the thiobarbituric acid-reactive substances produced by deoxyribose degradation and luminol-enhanced chemiluminescence, respectively. Compared with asbestos, wollastonite fibers produced higher ROS levels both in the PMN suspensions and in the cell-free reactive mixtures. A large amount of these ROS were not hydroxyl radicals. Indeed we obtained remarkable differences in ROS generation between unground and ground wollastonite fibers and negative results with fibers modified with ferric chloride and dithionite. In addition, ROS generation was partially inhibited (by 46-54%) in the reactions performed in the presence of 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl radical scavenger. Wollastonite fibers were also analyzed for their ability to lyse erythrocytes and activate complement. Hemolytic potency was about twice that of chrysotile and half that of crocidolite. The levels of complement activation (via the alternate pathway) were about four-fifths of those measured in zymosan-activated plasma (a typical stimulus used to activate the alternate pathway), equal to those obtained with crocidolite, and two-thirds of those found with chrysotile. The addition of DMTU markedly reduced both these activities. Since asbestos fiber toxicity is mainly due to hydroxyl radical generation, our results indicate that wollastonite fibers are probably less toxic than asbestos fibers.

In vitro effect of acrylonitrile on specific activities of human polymorphonuclear leucocytes.

N-Formyl-methionyl-leucyl-phenylalanine (F-MLP)-induced chemotaxis and luminolamplified chemiluminescence were studied in isolated human polymorphonuclear leucocytes (PMN) and exposed to acrylonitrile (ACN) in vitro. Chemotaxis was reduced at ACN concentrations of 3 mm and above, while respiratory burst was affected at ACN concentrations of 18mm and above. The ACN concentrations were highly correlated both with decreased chemotactic activity (r = 0.75; P < 0.05) and with decreased respiratory burst (r = 0.93; P < 0.01).

Biological effects of contaminated silicon carbide particles from a workstation in a plant producing abrasives.

A sample of silicon carbide dust taken in the field from a plant producing abrasives was studied in vitro. The SiC particles (part unmilled and part milled) were able to disturb the structure of erythrocyte membranes and to lead to blood red-cell lysis; they also either interfered with complement and activated the alternate pathway, or interacted with biological media and polymorphonuclear leucocyte membranes, thus eliciting reactive oxygen species production. These in vitro properties were detected both in original large particles and unmilled particles, over 40% of which were of respirable size. The ability of these SiC particles to produce complement activation in vitro lends support to the previous hypothesis, that the radiographic opacities found in two workers employed in the same area of the plant from which the dust tested was taken are due to a reaction by pulmonary interstitial structures to SiC particle inhalation. It is speculated that SiC particles could act like asbestos, the ability of which to activate complement through the alternate pathway is considered to be one of the mechanisms by which the initial asbestotic lesions and subsequent fibrotic inflammatory infiltrates are generated in the lung.