Contact complete integrability

Complete integrability in a symplectic setting means the existence of a Lagrangian foliation leaf-wise preserved by the dynamics. In the paper we describe complete integrability in a contact set-up as a more subtle structure: a flag of two foliations, Legendrian and co-Legendrian, and a holonomy-invariant transverse measure of the former in the latter. This turns out to be equivalent to the existence of a canonical $\R\ltimes \R^{n-1}$ structure on the leaves of the co-Legendrian foliation. Further, the above structure implies the existence of $n$ contact fields preserving a special contact 1-form, thus providing the geometric framework and establishing equivalence with previously known definitions of contact integrability. We also show that contact completely integrable systems are solvable in quadratures. We present an example of contact complete integrability: the billiard system inside an ellipsoid in pseudo-Euclidean space, restricted to the space of oriented null geodesics. We describe a surprising acceleration mechanism for closed light-like billiard trajectories

Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study

BACKGROUND: The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). METHODS: All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. RESULTS: 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p < 0.0001). The most frequently prescribed antiretrovirals were zidovudine with lamivudine (149; 25 %) and efavirenz [329, 55 %] at HCB and emtricitabine with tenofovir (899; 51 %) and efavirenz [681, 39 %] at RFH. At HCB, a median of 2 CD4 count measurements in the first year of cART were taken, compared to 5 at RFH (p < 0.0001). Median (IQR) CD4 cell increase after 12 months was +211 (+86, +359) and +212 (+105, +318) respectively. 287 (48 %) individuals from HCB and 1452 (82 %) from RFH had an available viral load measurement, of which 271 (94 %) and 1280 (88 %) were <400 copies/mL (p < 0.0001). After 36 months, comparable percentages had made at least one antiretroviral switch (77 % HCB vs. 78 % RFH; p = 0.23). However, switches for toxicity/patient choice were more common at RFH. After 12 and 36 months of cART 3 % and 8 % of individuals died at HCB, versus 2 % and 4 % at RFH (p < 0.0001). CONCLUSION: In middle-income countries, cART is usually started at an advanced stage of HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens

Selenium isotope evidence for pulsed flow of oxidative slab fluids

Isotope systematics of the redox sensitive and chalcophile element selenium (Se) were investigated on exhumed parts of subducted oceanic lithosphere to provide new constraints on slab dehydration conditions during subduction. The samples c,, show increasing delta(82/76)Se(NIST3149 )with higher abundances of fluid mobile elements, comprising a larger range (-1.89 to +0.48 parts per thousand) than that of mantle (-0.13 +/- 0.12 parts per thousand) and altered ocean crust (-0.35 to -0.07 parts per thousand). Our data point to pronounced, local scale redox variations within the subducting crust, wherein oxidative fluids dissolve sulfides and mobilise oxidised Se species. Subsequently recrystallising sulfides preferentially incorporate isotopically lighter, reduced Se, which shifts evolving fluids and late stage sulfides to higher delta Se-82/76(NIST3149). Redistribution of Se by repeated cydes of sulfide reworking within the subducted crust can be reconciled with episodes of oxidised fluid pulses from underlying slab mantle in modem subduction zones

Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man

The current test systems employed by pharmaceutical industry are poorly predictive for drug-induced liver injury (DILI). The ‘MIP-DILI’ project addresses this situation by the development of innovative preclinical test systems which are both mechanism-based and of physiological, pharmacological and pathological relevance to DILI in humans. An iterative, tiered approach with respect to test compounds, test systems, bioanalysis and systems analysis is adopted to evaluate existing models and develop new models that can provide validated test systems with respect to the prediction of specific forms of DILI and further elucidation of mechanisms. An essential component of this effort is the choice of compound training set that will be used to inform refinement and/or development of new model systems that allow prediction based on knowledge of mechanisms, in a tiered fashion. In this review, we focus on the selection of MIP-DILI training compounds for mechanism-based evaluation of non-clinical prediction of DILI. The selected compounds address both hepatocellular and cholestatic DILI patterns in man, covering a broad range of pharmacologies and chemistries, and taking into account available data on potential DILI mechanisms (e.g. mitochondrial injury, reactive metabolites, biliary transport inhibition, and immune responses). Known mechanisms by which these compounds are believed to cause liver injury have been described, where many if not all drugs in this review appear to exhibit multiple toxicological mechanisms. Thus, the training compounds selection offered a valuable tool to profile DILI mechanisms and to interrogate existing and novel in vitro systems for the prediction of human DILI

On Nonperturbative Calculations in Quantum Electrodynamics

A new approach to nonperturbative calculations in quantum electrodynamics is proposed. The approach is based on a regular iteration scheme for solution of Schwinger-Dyson equations for generating functional of Green functions. The approach allows one to take into account the gauge invariance conditions (Ward identities) and to perform the renormalization program. The iteration scheme can be realized in two versions. The first one ("perturbative vacuum") corresponds to chain summation in the diagram language. In this version in four-dimensional theory the non-physical singularity (Landau pole) arises which leads to the triviality of the renormalized theory. The second version ("nonperturbative vacuum") corresponds to ladder summation and permits one to make non-perturbative calculations of physical quantities in spite of the triviality problem. For chiral-symmetrical leading approximation two terms of the expansion of the first-step vertex function over photon momentum are calculated. A formula for anomalous magnetic moment is obtained. A problem of dynamical chiral symmetry breaking (DCSB) is considered, the calculations are performed for renormalized theory in Minkowsky space. In the strong coupling region DCSB-solutions arise. For the renormalized theory a DCSB-solution is also possible in the weak coupling region but with a subsidiary condition on the value of $\alpha$.Comment: 31 pages, Plain LaTex, no figures. Journal version: some discussion and refs. are adde

Release of oxidizing fluids in subduction zones recorded by iron isotope zonation in garnet

Subduction zones are key regions of chemical and mass transfer between the Earth’s surface and mantle. During subduction, oxidized material is carried into the mantle and large amounts of water are released due to the breakdown of hydrous minerals such as lawsonite. Dehydration accompanied by the release of oxidizing species may play a key role in controlling redox changes in the subducting slab and overlying mantle wedge. Here we present measurements of oxygen fugacity, using garnet–epidote oxybarometry, together with analyses of the stable iron isotope composition of zoned garnets from Sifnos, Greece. We find that the garnet interiors grew under relatively oxidized conditions whereas garnet rims record more reduced conditions. Garnet δ56Fe increases from core to rim as the system becomes more reduced. Thermodynamic analysis shows that this change from relatively oxidized to more reduced conditions occurred during lawsonite dehydration. We conclude that the garnets maintain a record of progressive dehydration and that the residual mineral assemblages within the slab became more reduced during progressive subduction-zone dehydration. This is consistent with the hypothesis that lawsonite dehydration accompanied by the release of oxidizing species, such as sulfate, plays an important and measurable role in the global redox budget and contributes to sub-arc mantle oxidation in subduction zones

Multi-lingual and multi-cultural information literacy; perspectives, models and good practice

Purpose This paper reviews current approaches to, and good practice, in information literacy development in multi-lingual and multi-cultural settings, with particular emphasis on provision for international students. Design/methodology/approach A selective and critical review of published literature is extended by evaluation of examples of multi-lingual information literacy tutorials and MOOCs. Findings Multi-lingual and multi-cultural information literacy are umbrella terms covering a variety of situations and issues. This provision is of increasing importance in an increasingly mobile and multi-cultural world. This article evaluates current approaches and good practice, focusing on issues of culture vis a vis language, the balance between individual and group needs, specific and generic information literacy instruction, and models for information literacy, pedagogy and culture. Recommendations for good practice and for further research are given, Originality/value This is one of very few articles critically reviewing how information literacy development is affected by linguistic and cultural factors

The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells

Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First, we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on 12.5 K fraction of PE-EVs: an elevated CD47 "don't eat me" signal (p < 0.01) and decreased exofacial phosphatidylserine "eat-me" signal (p < 0.001) were found along with decreased uptake of these PE-EVs (p < 0.05). The 12.5 K fraction of PE-EVs induced significantly lower chemotaxis (p < 0.01) and cell motility but accelerated cell adhesion of THP-1 cells (p < 0.05). The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia