Reaction-Diffusion System in a Vesicle with Semi-Permeable Membrane

We study the Schloegl model in a vesicle with semi-permeable membrane. The diffusion constant takes a smaller value in the membrane region, which prevents the outflow of self-catalytic product. A nonequilibrium state is stably maintained inside of the vesicle. Nutrients are absorbed and waste materials are exhausted through the membrane by diffusion. It is interpreted as a model of primitive metabolism in a cell.Comment: 8 pages, 6 figure

Individual differences in level of wisdom are associated with brain activation during a moral decision-making task.

IntroductionWisdom is reportedly associated with better health and quality of life. However, our knowledge of the neurobiology of wisdom is still in the early stages of development. We aimed to improve our understanding by correlating a psychometric measure of the trait with patterns of brain activation produced by a cognitive task theorized to be relevant to wisdom: moral decision-making. In particular, we aimed to determine whether individual differences in wisdom interact with moral task complexity in relation to brain activation.MethodsParticipants were 39 community-dwelling men and women aged 27-76 years, who completed moral and nonmoral decision-making tasks while undergoing functional magnetic resonance imaging. Brain activation in select regions of interest was correlated with participants' scores on the San Diego Wisdom Scale (SD-WISE).ResultsIndividual differences in wisdom were found to interact with brain response to moral versus nonmoral and moral personal versus impersonal dilemmas, particularly in regions in or near the default mode network. Persons with higher scores on the SD-WISE had less contrast between moral and nonmoral dilemmas and greater contrast between moral-personal and moral-impersonal dilemmas than individuals with lower SD-WISE scores.ConclusionsResults confirmed our hypothesis that individual differences in level of wisdom would interact with moral condition in relation to brain activation, and may underscore the relevance of considering one's own and others' actions and experiences in the context of wise thinking. Future studies are needed to replicate these findings and to examine specific neurocircuits

Assessing Semantic Similarities among Geospatial Feature Class Definitions

The assessment of semantic similarity among objects is a basic requirement for semantic interoperability. This paper presents an innovative approach to semantic similarity assessment by combining the advantages of two different strategies: featurematching process and semantic distance calculation. The model involves a knowledge base of spatial concepts that consists of semantic relations (is-a and part-whole) and distinguishing features (functions, parts, and attributes). By taking into consideration cognitive properties of similarity assessments, this model expects to represent a cognitively plausible and computationally achievable method for measuring the degree of interoperability

Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial

BACKGROUND: Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefits of protease inhibitor monotherapy in long-term clinical use: in particular, the effect on drug resistance and future treatment options. METHODS: In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (≥18 years of age) positive for HIV attending 43 public sector treatment centres in the UK who had suppressed viral load (<50 copies per mL) for at least 24 weeks on combination ART with no change in the previous 12 weeks and a CD4 count of more than 100 cells per μL. Participants were randomly allocated (1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to combination treatment if viral load rebounded. All treatments were oral. Randomisation was with permuted blocks of varying size and stratified by centre and baseline ART; we used a computer-generated, sequentially numbered randomisation list. The primary outcome was loss of future drug options, defined as new intermediate-level or high-level resistance to one or more drugs to which the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non-inferiority margin of 10%). We estimated probability of rebound and resistance with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN04857074. FINDINGS: Between Nov 4, 2008, and July 28, 2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3 years, one or more future drug options had been lost in two participants (Kaplan-Meier estimate 0·7%) in the OT group and six (2·1%) in the PI-mono group: difference 1·4% (-0·4 to 3·4); non-inferiority shown. 49 (16·8%) participants in the OT group and 65 (22·0%) in the PI-mono group had grade 3 or 4 clinical adverse events (difference 5·1% [95% CI -1·3 to 11·5]; p=0·12); 45 (six treatment related) and 56 (three treatment related) had serious adverse events. INTERPRETATION: Protease inhibitor monotherapy, with regular viral load monitoring and prompt reintroduction of combination treatment for rebound, preserved future treatment options and did not change overall clinical outcomes or frequency of toxic effects. Protease inhibitor monotherapy is an acceptable alternative for long-term clinical management of HIV infection. FUNDING: National Institute for Health Research

Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT).

BACKGROUND: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. METHODS: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. FINDINGS: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference -0.6%, 95% CI -3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. INTERPRETATION: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Search for the K(L) --> PI0 PI0 E+ E- Decay in the KTeV Experiment

The recent discovery of a large CP violating asymmetry in K(L) --> PI+ PI- E+ E- mode has prompted us to seach for the associated K(L) --> PI0 PI0 E+ E- decay mode in the KTeV-E799 experiment at Fermilab. In 2.7E+11 K(L) decays, one candidate event has been observed with an expected background of 0.3 event, resulting in an upper limit for the K(L) --> PI0 PI0 E+ E- branching ratio of 6.6E-09 at the 90% confidence level.Comment: To be published in Phys. Rev. Let

Gas absorption and dust extinction towards the Orion Nebula Cluster

B. Hasenberger, et al, 'Gas absorption and dust extinction towards the Orion Nebula Cluster', Astronomy & Astrophysics, 593, A7, 2016. The version of record is available online at DOI: 10.1051/0004-6361/201628517. Published by EDP Sciences. © ESO, 2016We characterise the relation between the gas and dust content of the interstellar medium towards young stellar objects in the Orion Nebula Cluster. X-ray observations provide estimates of the absorbing equivalent hydrogen column density N_H based on spectral fits. Near-infrared extinction values are calculated from intrinsic and observed colour magnitudes (J-H) and (H-K_s) as given by the VISTA Orion A survey. A linear fit of the correlation between column density and extinction values A_V yields an estimate of the N_H/A_V ratio. We investigate systematic uncertainties of the results by describing and (if possible) quantifying the influence of circumstellar material and the adopted extinction law, X-ray models, and elemental abundances on the N_H/A_V ratio. Assuming a Galactic extinction law with R_V=3.1 and solar abundances by Anders & Grevesse (1989), we deduce an N_H/A_V ratio of (1.39 +- 0.14) x 10^21 cm^-2 mag^-1 for Class III sources in the Orion Nebula Cluster where the given error does not include systematic uncertainties. This ratio is consistent with similar studies in other star-forming regions and approximately 31% lower than the Galactic value. We find no obvious trends in the spatial distribution of N_H/A_V ratios. Changes in the assumed extinction law and elemental abundances are demonstrated to have a relevant impact on deduced A_V and N_H values, respectively. Large systematic uncertainties associated with metal abundances in the Orion Nebula Cluster represent the primary limitation for the deduction of a definitive N_H/A_V ratio and the physical interpretation of these results.Peer reviewe