Nanoparticulate CpG Immunotherapy in RAO- Affected Horses: Phase I and IIa Study

Background: Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results. Objectives: The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment. Animals and Methods: Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III). Results: At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure. Conclusion and Clinical Importance: Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans

Selective methane oxidation over promoted oxide catalysts. Quarterly report, March 1 - May 31, 1996

Series of catalysts consisting of MoO{sub 3}, V{sub 2}O{sub 5}, TiO{sub 2}, and SnO{sub 2} impregnated onto oxide supports consisting of SiO{sub 2} (Cab-O-Sil), TiO{sub 2} or SnO{sub 2} were previously prepared and tested for the selective oxidation of methane to oxygenates, and it was found that the V{sub 2}O{sub 5}/SiO{sub 2} catalyst was the most active and most selective toward the formation of formaldehyde. These catalysts have been characterized by laser Raman spectroscopy after dehydration and during the methane oxidation reaction with a CH{sub 4}/02 = 10/1 reaction mixture at 500{degrees}C in a continuous flow in situ reaction cell. With the V{sub 2}O{sub 5}/SiO{sub 2} catalyst (the most active catalyst among those studied), no significant structural changes were revealed by in situ Raman analyses, indicating that the fully oxidized surface sites were related to the high formaldehyde selectivivity. Over the V{sub 2}O{sub 5}/TiO{sub 2} and V{sub 2}O{sub 5}/SnO{sub 2} catalysts, CO and CO{sub 2} were the principal products produced by oxidation of methane. For the first time, in situ Raman analysis clearly showed that for these latter catalysts, the surface vanadium(V) oxide species were partially reduced under the steady-state reaction conditions. The performance of the V{sub 2}O{sub 5}/TiO{sub 2}/SiO{sub 2} catalyst was similar to that of the V{sub 2}O{sub 5}TiO{sub 2} catalyst, consistent with the earlier observation that vanadia was largely bound to the titania overlayer. It appears that formaldehyde selectivity decreased with increasing catalyst reducibility, but no direct correlation of catalyst activity with reductibility was observed

Grounding Evaluation Capacity Development in Systems Theory

While “systemic thinking” is popular in the context of capacity development and evaluation, there is currently a lack of understanding about the benefits to employing systems theory in evaluation capacity development. Systems theory provides a useful orientation to the work involved in complex systems (e.g. national evaluation systems). This article illustrates how evaluation capacity development practitioners can use systems theory as a conceptual tool to gain a better understanding of the functional aspects and interrelationships present within a given evaluation system. Specifically, the systems theory perspective can help elucidate the reasons for the success or failure of a given evaluation capacity development program or activity. With the goal of motivating evaluation capacity development practitioners to use systems theory in their work, this article presents a systems theory framework for evaluation capacity development and offers practical examples of how it can be adopted

Proton acceleration by irradiation of isolated spheres with an intense laser pulse

We report on experiments irradiating isolated plastic spheres with a peak laser intensity of 2-3 x 10(20) W cm(-2). With a laser focal spot size of 10 mu m full width half maximum (FWHM) the sphere diameter was varied between 520 nm and 19.3 mu m. Maximum proton energies of similar to 25 MeV are achieved for targets matching the focal spot size of 10 mu m in diameter or being slightly smaller. For smaller spheres the kinetic energy distributions of protons become nonmonotonic, indicating a change in the accelerating mechanism from ambipolar expansion towards a regime dominated by effects caused by Coulomb repulsion of ions. The energy conversion efficiency from laser energy to proton kinetic energy is optimized when the target diameter matches the laser focal spot size with efficiencies reaching the percent level. The change of proton acceleration efficiency with target size can be attributed to the reduced cross-sectional overlap of subfocus targets with the laser. Reported experimental observations are in line with 3D3V particle in cell simulations. They make use of well-defined targets and point out pathways for future applications and experiments.DFG via the Cluster of Excellence Munich-Centre for Advanced Photonics (MAP) Transregio SFB TR18NNSA DE-NA0002008Super-MUC pr48meIvo CermakCGC Instruments in design and realization of the Paul trap systemIMPRS-APSLMUexcellent Junior Research FundDAAD|ToIFEEuropean Union's Horizon research and innovation programme 633053Physic

From nonwetting to prewetting: the asymptotic behavior of 4He drops on alkali substrates

We investigate the spreading of 4He droplets on alkali surfaces at zero temperature, within the frame of Finite Range Density Functional theory. The equilibrium configurations of several 4He_N clusters and their asymptotic trend with increasing particle number N, which can be traced to the wetting behavior of the quantum fluid, are examined for nanoscopic droplets. We discuss the size effects, inferring that the asymptotic properties of large droplets correspond to those of the prewetting film

Functional Characterization of Rare Variants in the SHOX2 Gene Identified in Sinus Node Dysfunction and Atrial Fibrillation

Sinus node dysfunction (SND) and atrial fibrillation (AF) often coexist; however, the molecular mechanisms linking both conditions remain elusive. Mutations in the homeobox-containing SHOX2 gene have been recently associated with early-onset and familial AF. Shox2 is a key regulator of sinus node development, and its deficiency leads to bradycardia, as demonstrated in animal models. To provide an extended SHOX2 gene analysis in patients with distinct arrhythmias, we investigated SHOX2 as a susceptibility gene for SND and AF by screening 98 SND patients and 450 individuals with AF. The functional relevance of the novel mutations was investigated in vivo and in vitro, together with the previously reported p.H283Q variant. A heterozygous missense mutation (p.P33R) was identified in the SND cohort and four heterozygous variants (p.G77D, p.L129=, p.L130F, p.A293=) in the AF cohort. Overexpression of the pathogenic predicted mutations in zebrafish revealed pericardial edema for p.G77D and the positive control p.H283Q, whereas the p.P33R and p.A293= variants showed no effect. In addition, a dominant-negative effect with reduced heart rates was detected for p.G77D and p.H283Q. In vitro reporter assays demonstrated for both missense variants p.P33R and p.G77D significantly impaired transactivation activity, similar to the described p.H283Q variant. Also, a reduced Bmp4 target gene expression was revealed in zebrafish hearts upon overexpression of the p.P33R mutant. This study associates additional rare variants in the SHOX2 gene implicated in the susceptibility to distinct arrhythmias and allows frequency estimations in the AF cohort (3/990). We also demonstrate for the first time a genetic link between SND and AF involving SHOX2. Moreover, our data highlight the importance of functional investigations of rare variants

The design, construction and performance of the MICE scintillating fibre trackers

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 ElsevierCharged-particle tracking in the international Muon Ionisation Cooling Experiment (MICE) will be performed using two solenoidal spectrometers, each instrumented with a tracking detector based on diameter scintillating fibres. The design and construction of the trackers is described along with the quality-assurance procedures, photon-detection system, readout electronics, reconstruction and simulation software and the data-acquisition system. Finally, the performance of the MICE tracker, determined using cosmic rays, is presented.This work was supported by the Science and Technology Facilities Council under grant numbers PP/E003214/1, PP/E000479/1, PP/E000509/1, PP/E000444/1, and through SLAs with STFC-supported laboratories. This work was also supportedby the Fermi National Accelerator Laboratory, which is operated by the Fermi Research Alliance, under contract No. DE-AC02-76CH03000 with the U.S. Department of Energy, and by the U.S. National Science Foundation under grants PHY-0301737,PHY-0521313, PHY-0758173 and PHY-0630052. The authors also acknowledge the support of the World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan

Postnatal depression across countries and cultures : a qualitative study

Background: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. Aims: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people’s perceptions of remedies and services for morbid states of unhappiness within the context of local services. Method: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals.Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. Results: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. Conclusions: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research

To wet or not to wet: that is the question

Wetting transitions have been predicted and observed to occur for various combinations of fluids and surfaces. This paper describes the origin of such transitions, for liquid films on solid surfaces, in terms of the gas-surface interaction potentials V(r), which depend on the specific adsorption system. The transitions of light inert gases and H2 molecules on alkali metal surfaces have been explored extensively and are relatively well understood in terms of the least attractive adsorption interactions in nature. Much less thoroughly investigated are wetting transitions of Hg, water, heavy inert gases and other molecular films. The basic idea is that nonwetting occurs, for energetic reasons, if the adsorption potential's well-depth D is smaller than, or comparable to, the well-depth of the adsorbate-adsorbate mutual interaction. At the wetting temperature, Tw, the transition to wetting occurs, for entropic reasons, when the liquid's surface tension is sufficiently small that the free energy cost in forming a thick film is sufficiently compensated by the fluid- surface interaction energy. Guidelines useful for exploring wetting transitions of other systems are analyzed, in terms of generic criteria involving the "simple model", which yields results in terms of gas-surface interaction parameters and thermodynamic properties of the bulk adsorbate.Comment: Article accepted for publication in J. Low Temp. Phy

The course of mental health after miscarriage and induced abortion: a longitudinal, five-year follow-up study

BACKGROUND: Miscarriage and induced abortion are life events that can potentially cause mental distress. The objective of this study was to determine whether there are differences in the patterns of normalization of mental health scores after these two pregnancy termination events. METHODS: Forty women who experienced miscarriages and 80 women who underwent abortions at the main hospital of Buskerud County in Norway were interviewed. All subjects completed the following questionnaires 10 days (T1), six months (T2), two years (T3) and five years (T4) after the pregnancy termination: Impact of Event Scale (IES), Quality of Life, Hospital Anxiety and Depression Scale (HADS), and another addressing their feelings about the pregnancy termination. Differential changes in mean scores were determined by analysis of covariance (ANCOVA) and inter-group differences were assessed by ordinary least squares methods. RESULTS: Women who had experienced a miscarriage had more mental distress at 10 days and six months after the pregnancy termination than women who had undergone an abortion. However, women who had had a miscarriage exhibited significantly quicker improvement on IES scores for avoidance, grief, loss, guilt and anger throughout the observation period. Women who experienced induced abortion had significantly greater IES scores for avoidance and for the feelings of guilt, shame and relief than the miscarriage group at two and five years after the pregnancy termination (IES avoidance means: 3.2 vs 9.3 at T3, respectively, p < 0.001; 1.5 vs 8.3 at T4, respectively, p < 0.001). Compared with the general population, women who had undergone induced abortion had significantly higher HADS anxiety scores at all four interviews (p < 0.01 to p < 0.001), while women who had had a miscarriage had significantly higher anxiety scores only at T1 (p < 0.01). CONCLUSION: The course of psychological responses to miscarriage and abortion differed during the five-year period after the event. Women who had undergone an abortion exhibited higher scores during the follow-up period for some outcomes. The difference in the courses of responses may partly result from the different characteristics of the two pregnancy termination events