Patents and Competition in the Automobile Industry

Methane (CH4) fluxes from world rivers are still poorly constrained, with measurements restricted mainly to temperate climates. Additional river flux measurements, including spatio-temporal studies, are important to refine extrapolations. Here we assess the spatio-temporal variability of CH4 fluxes from the Amazon and its main tributaries, the Negro, Solimoes, Madeira, Tapajos, Xingu, and Para Rivers, based on direct measurements using floating chambers. Sixteen of 34 sites were measured during low and high water seasons. Significant differences were observed within sites in the same river and among different rivers, types of rivers, and seasons. Ebullition contributed to more than 50% of total emissions for some rivers. Considering only river channels, our data indicate that large rivers in the Amazon Basin release between 0.40 and 0.58 Tg CH4 yr(-1). Thus, our estimates of CH4 flux from all tropical rivers and rivers globally were, respectively, 19-51% to 31-84% higher than previous estimates, with large rivers of the Amazon accounting for 22-28% of global river CH4 emissions.Funding Agencies|FAPESP [08/58089-9, 2011/06609-1, 2011/14502-2, 2012/17359-9]</p

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

Macdonald Polynomials from Sklyanin Algebras: A Conceptual Basis for the pp-Adics-Quantum Group Connection

We establish a previously conjectured connection between $p$-adics and quantum groups. We find in Sklyanin's two parameter elliptic quantum algebra and its generalizations, the conceptual basis for the Macdonald polynomials, which ``interpolate'' between the zonal spherical functions of related real and $p$\--adic symmetric spaces. The elliptic quantum algebras underlie the $Z_n$\--Baxter models. We show that in the n \air \infty limit, the Jost function for the scattering of {\em first} level excitations in the $Z_n$\--Baxter model coincides with the Harish\--Chandra\--like $c$\--function constructed from the Macdonald polynomials associated to the root system $A_1$. The partition function of the $Z_2$\--Baxter model itself is also expressed in terms of this Macdonald\--Harish\--Chandra\ $c$\--function, albeit in a less simple way. We relate the two parameters $q$ and $t$ of the Macdonald polynomials to the anisotropy and modular parameters of the Baxter model. In particular the $p$\--adic ``regimes'' in the Macdonald polynomials correspond to a discrete sequence of XXZ models. We also discuss the possibility of ``$q$\--deforming'' Euler products.Comment: 25 page

Midlife and Late-Life Vascular Risk Factors and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study.

BACKGROUND: Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity. METHODS AND RESULTS: We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity. CONCLUSIONS: Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life

Classes of fast and specific search mechanisms for proteins on DNA

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

Summer CO2 evasion from streams and rivers in the Kolyma River basin, north-east Siberia

Inland water systems are generally supersaturated in carbon dioxide (CO2) and are increasingly recognized as playing an important role in the global carbon cycle. The Arctic may be particularly important in this respect, given the abundance of inland waters and carbon contained in Arctic soils; however, a lack of trace gas measurements from small streams in the Arctic currently limits this understanding.We investigated the spatial variability of CO2 evasion during the summer low-flow period from streams and rivers in the northern portion of the Kolyma River basin in north-eastern Siberia. To this end, partial pressure of carbon dioxide (pCO2) and gas exchange velocities (k) were measured at a diverse set of streams and rivers to calculate CO2 evasion fluxes. We combined these CO2 evasion estimates with satellite remote sensing and geographic information system techniques to calculate total areal CO2 emissions. Our results show that small streams are substantial sources of atmospheric CO2 owing to high pCO2 and k, despite being a small portion of total inland water surface area. In contrast, large rivers were generally near equilibrium with atmospheric CO2. Extrapolating our findings across the Panteleikha-Ambolikha sub-watersheds demonstrated that small streams play a major role in CO2 evasion, accounting for 86% of the total summer CO2 emissions from inland waters within these two sub-watersheds. Further expansion of these regional CO2 emission estimates across time and space will be critical to accurately quantify and understand the role of Arctic streams and rivers in the global carbon budget

Meaning-making from wordless (or nearly wordless) picturebooks: what educational research expects and what readers have to say

Wordless (or nearly wordless) picturebooks are intriguing in terms of how readers make meaning from them. This article offers a conceptualization of existing studies in the field of education that use wordless picturebooks with young readers. While some of these studies contribute to understanding meaning-making, the pragmatic use of wordless picturebooks often does not take account of their particular nature and of the heightened role of the reader, leading to a mismatch between what the picturebook expects from the implied reader and the researchers’ expectations of what ‘real’ readers must do with these books. By highlighting observations from children’s literature scholarship and reader-response studies, this article aims to encourage a more interdisciplinary understanding of meaning-making. It also seeks to persuade educational researchers and mediators to consider investigative approaches that are not based on verbalization but are more in tune with the invitations that wordless picturebooks extend to young readers

Evaluation of the possibility of using diatomite natural mineral as a composite agent in acrylic coating

WOS: 000427736200014In the present study the possibility of the commercially available acryl and diatomite earth (DE) mineral as a composite coating for corrosion protection of Mg alloys has been evaluated. The acrylic coating is used as a top coating in a wide field of applications like automotive, aerospace, medicine and electronics where it shows beneficial properties. Diatomite-dispersed acrylic paint was applied over the substrate by conventional spray technique with an air pressure of 3 kg cm(-2). Firstly the acryl was mixed with hardener and then the DE was added to the mixture. Four types of coating with 0, 2, 4, 8 g/L DE have been prepared. The results show that adding up to 4 g/L of the DE improved the corrosion resistance and produced a coating with acceptable surface roughness