Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Linking livelihood strategies with a regional level landscape mosaic to explore trade-offs between forest conservation and human wellbeing in a Madagascar biodiversity hotspot

The north-eastern escarpment of Madagascar contains the island’s last remaining large-scale humid forest massifs surrounded by diverse small-scale agricultural mosaics. There is high deforestation mainly caused by shifting cultivation practiced by local land users to produce upland rice for subsistence. Today, large protected areas restrict land users’ access to forests to collect wood and other forest products. Moreover, they are no more able to expand their cultivated land, which leads to shorter shifting cultivation cycles and decreasing plot sizes for irrigated rice and cash crop cultivation. Cash crop production of clove and vanilla is exposed to risks such as extreme inter-annual price fluctuations, pests and cyclones. In the absence of work opportunities, agricultural extension services and micro-finance schemes people are stuck in a poverty trap. New development strategies are needed to mitigate the trade-offs between forest conservation and human well-being. As landscape composition and livelihood strategies vary across the region, these strategies need to be spatially differentiated to avoid implementing generic solutions, which do not fit the local context. However, up to date, little is known about the spatial patterns of shifting cultivation and other land use systems at the regional level. This is mainly due to the high spatial and temporal dynamics inherent to shifting cultivation, which makes it difficult to monitor the dynamics of this land use system with remote sensing methods. Furthermore, knowledge about land users’ livelihood strategies and the risks and opportunities they face stems from very few local case studies. To overcome this challenge, firstly, we used remote sensing data and a landscape mosaic approach to delineate the main landscape types at the regional level. Secondly, we developed a land user typology based on socio-ecological data from household surveys in 45 villages spread throughout the region. Combining the land user typology with the landscape mosaic map allowed us to reveal spatial patterns of the interaction between landscapes and people and to better understand the trade-offs between forest conservation and local wellbeing. While shifting cultivation systems are being transformed into more intensive permanent agricultural systems in many countries around the globe, Madagascar seems to be an exception to this trend. Linking land cover information to human-environmental interactions over large areas is crucial to designing policies and to inform decision making for a more sustainable development of this resource-rich but poverty-prone context.

Proliferative kidney disease in brown trout – infection level, pathology and mortality under field conditions

Proliferative kidney disease (PKD) is an emerging disease threatening wild salmonid populations. In temperature-controlled aquaria, PKD can cause mortality rates of up to 85% in rainbow trout. So far, no data about PKD-related mortality in wild brown trout Salmo trutta fario are available. The aim of this study was to investigate mortality rates and pathology in brown trout kept in a cage within a natural river habitat known to harbor Tetracapsuloides bryosalmonae. Young-of-the-year (YOY) brown trout, free of T. bryosalmonae, were exposed in the River Wutach, in the northeast of Switzerland, during 3 summer months. Samples of wild brown trout caught by electrofishing near the cage location were examined in parallel. The incidence of PKD in cage-exposed animals (69%) was not significantly different to the disease prevalence of wild fish (82 and 80% in the upstream and downstream locations, respectively). The mortality in cageexposed animals, however, was as low as 15%. At the termination of the exposure experiment, surviving fish showed histological lesions typical for PKD regression, suggesting that many YOY brown trout survive the initial infection. Our results at the River Wutach suggest that PKD in brown trout does not always result in high mortality under natural conditions.

Inter-acción : lenguaje oral y pedagogía teatral

Esta investigación aplicada, mantuvo la línea de trabajo que se viene sosteniendo desde el período 05/07 y pretendió profundizar el sesgo de la pedagogía teatral orientada a interaccionar con aprendizajes lingüísticos, fundamentalmente del discurso oral. Se trabajó con un grupo de muestra acotado, probando una secuencia pedagógico-didáctica que diera resultados que permitieran afirmar que el lenguaje Teatro posibilita, en la escuela, la investigación guiada de “los modos en los que el afuera interviene en la conformación del adentro" y facilita a los alumnos desarrollar su oralidad y gestualidad en el nivel interaccional, impactando positivamente en su desempeño académico y social.

Rural to Urban Migration: A District Level Analysis for India

Based on the recent census data this paper analyses the district level rural to urban migration rates (both intra-state and the inter-state) among males and females separately. Both the rates are closely associated irrespective of whether the migrants originate from the rural areas within the state or outside the state. This would suggest that women usually migrate as accompanists of the males. Though many of the relatively poor and backward states actually show large population mobility, which is primarily in search of a livelihood, the mobility of male population is also seen to be prominent in the relatively advanced states like Maharashtra and Gujarat. Rapid migration of rural females within the boundaries of the states is, however, evident across most of the regions. The social networks, which play an important role in the context of migration are prevalent among the short distance migrants and tend to lose their significance with a rise in the distance between the place of origin and destination though there are some exceptions to this phenomenon. Besides the north-south divide in the Indian context is indeed a significant phenomenon with a few exceptions of metropolitan cities. As regards the effect of factors at the place of destination, prospects for better job opportunities are a major determinant of male migration. Low castes and minority groups tend to pull migration through network effects. Among females also these effects are evident though with the inclusion of the male migration rate they become less significant. Finally the paper brings out the policy implications.

Skill sorting, inter-industry skill wage premium, and production chains: evidence from India 1999-2000

This paper proposes a mechanism that links industry’s technological characteristics (i.e. quality of non-labor inputs, which is proxied by the length of industry production chains), industry-specific skill wage premium, and skill sorting across industries. It is hypothesized that high-skilled workers are sorted into industries where they can receive a higher skill wage premium, by working with better quality non-labor input. The quality of non-labor inputs is assumed to be worse in industries with longer production chains due to the increased involvement of low-skilled labor and poor infrastructure over the sequential production. By examining Indian wage and employment data for 1999-2000, empirical evidence to support this mechanism can be obtained: First, the skill wage premium is lower [higher] in industries with longer [shorter] production chains. Second, the skill wage premium is lower [higher] in industries with a higher [lower] proportion of low-skilled workers producing inputs outside their own industry. Third, the proportion of high-skilled workers is larger in industries with shorter production chains and lower ratio of low-skilled labor involved, i.e., a skill sorting trend can be observed.

Compilation of a regionally-extended inter-country input-output table and its application to global value chain analysis

Studies on the rise of global value chains (GVCs) have attracted a great deal of interest in the recent economics literature. However, due to statistical and methodological challenges, most existing research ignores domestic regional heterogeneity in assessing the impact of joining GVCs. GVCs are supported not only directly by domestic regions that export goods and services to the world market, but also indirectly by other domestic regions that provide parts, components, and intermediate services to final exporting regions. To better understand the nature of a country's position and degree of participation in GVCs, we need to fully examine the role of individual domestic regions. Understanding the domestic components of GVCs is especially important for larger economies such as China, the US, India and Japan, where there may be large variations in economic scale, geography of manufacturing, and development stages at the domestic regional level. This paper proposes a new framework for measuring domestic linkages to global value chains. This framework measures domestic linkages by endogenously embedding a target country's (e.g. China and Japan) domestic interregional input–output tables into the OECD inter-country input–output model. Using this framework, we can more clearly understand how global production is fragmented and extended internationally and domestically.

The secret to legal foretelling: generic and inter-generic aspects of vagueness in contracts, patents and regulations

In this genre analysis research paper, we compare U.S. patents, contracts, and regulations on technical matters with a focus upon the relation between vagueness and communicative purposes and subpurposes of these three genres. Our main interest is the investigation of intergeneric conventions across the three genres, based on the software analysis of three corpora (one for each genre, 1 million words per corpus). The result of the investigation is that intergeneric conventions are found at the level of types of expressed linguistic vagueness, but that intergeneric conventions at the level of actual formulations are rare. The conclusion is that at this latter level the influence from the situation type underlying the individual genre is more important than the overarching legal character of the genres, when we talk about introducing explicit vagueness in the text.

Inter-operator reliability of live football match statistics from OPTA Sportsdata

The aim of the study was to evaluate the inter-operator reliability of OPTA Client System which is used to collect live football match statistics by OPTA Sportsdata Company. Two groups of experienced operators were required to analyze a Spanish league match independently. Results showed that team events coded by independent operators reached a very good agreement (kappa values were 0.92 and 0.94) and average difference of event time was 0.06±0.04 s. The reliability of goalkeeper actions was also at high level, kappa values were 0.92 and 0.86. The high intra-class correlation coefficients (ranged from 0.88 to 1.00) and low standardized typical errors (varied from 0.00 to 0.37) of different match actions and indicators of individual outfield players showed a high level of inter-operator reliability as well. These results suggest that the OPTA Client System is reliable to be used to collect live football match statistics by well trained operators.

Analyzing size-symmetric vs. size-asymmetric and intra-vs. inter-specific competition in beech (Fagus sylvatica L.) mixed stands

In mixed stands, inter-specific competition can be lower than intra-specific competition when niche complementarity and/or facilitation between species prevail. These positive interactions can take place at belowground and/or aboveground levels. Belowground competition tends to be size symmetric while the aboveground competition is usually for light and almost always size-asymmetric. Interactions between forest tree species can be explored analyzing growth at tree level by comparing intra and inter-specific competition. At the same time, possible causes of niche complementarity can be inferred relating intra and inter-specific competition with the mode of competition, i.e. size-symmetric or sizeasymmetric. The aim of this paper is to further our understanding of the interactions between species and to detect possible causes of competition reduction in mixed stands of beech (Fagus sylvatica L.) with other species: pine?beech, oak?beech and fir?beech. To test whether species growth is better explained by size-symmetric and/or size-asymmetric competition, five different competition structures where included in basal area growth models fitted using data from the Spanish National Forest Inventory for the Pyrenees. These models considered either size-symmetry only (Reineke?s stand density index, SDI), size-asymmetry only (SDI of large trees or SDI of small trees), or both combined. In order to assess the influence of the admixture, these indices were introduced in two different ways, one of which was to consider that trees of all species compete in a similar way, and the other was to split the stand density indices into intra- and inter-specific competition components. The results showed that in pine?beech mixtures, there is a slightly negative effect of beech on pine basal area growth while beech benefitted from the admixture of Scots pine; this positive effect being greater as the proportion of pine trees in larger size classes increases. In oak?beech mixtures, beech growth was also positively influenced by the presence of oaks that were larger than the beech trees. The growth of oak, however, decreased when the proportion of beech in SDI increased, although the presence of beech in larger size classes promoted oak growth. Finally, in fir?beech mixtures, neither fir nor beech basal area growth were influenced by the presence of the other species. The results indicate that size-asymmetric is stronger than size-symmetric competition in these mixtures, highlighting the importance of light in competition. Positive species interactions in size-asymmetric competition involved a reduction of asymmetry in tree size-growth relationships.

Exploring users inter-temporal preferences for measuring transport social equity effects

There exist different ways for defining a welfare function. Traditionally, welfare economic theory foundation is based on the Net Present Value (NPV) calculation where the time dependent preferences of considered agents are taken into account. However, the time preferences, remains a controversial subject. Currently, the traditional approach employs a unique discount rate for various agents. Nevertheless, this way of discounting appears inconsistent with sustainable development. New research work suggests that the discount rate may not be a homogeneous value. The discount rates may change following the individual’s preferences. A significant body of evidence suggests that people do not behave following a constant discount rate. In fact, UK Government has quickly recognized the power of the arguments for time-varying rates, as it has done in its official guidance to Ministries on the appraisal of investments and policies. Other authors deal with not just time preference but with uncertainty about future income (precautionary saving). In a situation in which economic growth rates are similar across time periods, the rationale for declining social optimal discount rates is driven by the preferences of the individuals in the economy, rather than expectations of growth. However, these approaches have been mainly focused on long-term policies where intergenerational risks may appear. The traditional cost-benefit analysis (CBA) uses a unique discount rate derived from market interest rates or investment rates of return for discounting the costs and benefits of all social agents included in the CBA. However, recent literature showed that a more adequate measure of social benefit is possible by using different discount rates including inter-temporal preferences rate of users, private investment discount rate and intertemporal preferences rate of government. Actually, the costs of opportunity may differ amongst individuals, firms, governments, or society in general, as do the returns on savings. In general, the firms or operators require an investment rate linked to the current return on savings, while the discount rate of consumers-users depends on their time preferences with respect of the current and the future consumption, as well as society can take into account the intergenerational well-being, adopting a lower discount rate for today’s generation. Time discount rate of social actors (users, operators, government and society) places a lower value in a future gain, but the uncertainty about future income strongly determines the individual preferences. These time and uncertainty depends on preferences and should be integrated into a transport policy formulation that may have significant social impacts. The discount rate of a user cannot be the same than the operator’s discount rate. The preferences of both are different. In addition, another school of thought suggests that people, such as a social group, may have different attitudes towards future costs and benefits. Particularly, the users have different discount rates related to their income. Some research work tried to modify user discount rates using a compensating weight which represents the inverse of household income level. The inter-temporal preferences are a proxy of the willingness to pay during the time. Its consideration is important in order to make acceptable or not a policy or investment

Dynamic mapping at the laminar level of odor-elicited responses in rat olfactory bulb by functional MRI

We have applied functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) image-contrast to map odor-elicited olfactory responses at the laminar level in the rat olfactory bulb (OB) elicited by iso-amyl acetate (10−2 dilution of saturated vapor) with spatial and temporal resolutions of 220×220×1,000 μm and 36 s. The laminar structure of the OB was clearly depicted by high-resolution in vivo anatomical MRI with spatial resolution of 110×110×1,000 μm. In repeated BOLD fMRI measurements, highly significant (P < 0.001) foci were located in the outer layers of both OBs. The occurrence of focal OB activity within a domain at the level of individual glomeruli or groups of glomeruli was corroborated on an intra- and inter-animal basis under anesthetized conditions with this noninvasive method. The dynamic studies demonstrated that the odor-elicited BOLD activations were highly reproducible on a time scale of minutes, whereas over tens of minutes the activations sometimes varied slowly. We found large BOLD signal (ΔS/S = 10–30%) arising from the olfactory nerve layer, which is devoid of synapses and composed of unmyelinated fibers and glial cells. Our results support previous studies with other methods showing that odors elicit activity within glomerular layer domains in the mammalian OB, and extend the analysis to shorter time periods at the level of individual glomeruli or groups of glomeruli. With further improvement, BOLD fMRI should be ideal for systematic analysis of the functional significance of individual glomeruli in olfactory information encoding and of spatiotemporal processing within the olfactory system.

Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy

The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288; 288E → K). When examined using the 288E → K receptor, the efficacies of both PD135,158 and L-740,093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.

Striking sequence similarity in inter- and intra-specific comparisons of class I SLG alleles from Brassica oleracea and Brassica campestris: Implications for the evolution and recognition mechanism

Self-incompatibility in Brassica is controlled by a single multi-allelic locus (S locus), which contains at least two highly polymorphic genes expressed in the stigma: an S glycoprotein gene (SLG) and an S receptor kinase gene (SRK). The putative ligand-binding domain of SRK exhibits high homology to the secretory protein SLG, and it is believed that SLG and SRK form an active receptor kinase complex with a self-pollen ligand, which leads to the rejection of self-pollen. Here, we report 31 novel SLG sequences of Brassica oleracea and Brassica campestris. Sequence comparisons of a large number of SLG alleles and SLG-related genes revealed the following points. (i) The striking sequence similarity observed in an inter-specific comparison (95.6% identity between SLG14 of B. oleracea and SLG25 of B. campestris in deduced amino acid sequence) suggests that SLG diversification predates speciation. (ii) A perfect match of the sequences in hypervariable regions, which are thought to determine S specificity in an intra-specific comparison (SLG8 and SLG46 of B. campestris) and the observation that the hypervariable regions of SLG and SRK of the same S haplotype were not necessarily highly similar suggests that SLG and SRK bind different sites of the pollen ligand and that they together determine S specificity. (iii) Comparison of the hypervariable regions of SLG alleles suggests that intragenic recombination, together with point mutations, has contributed to the generation of the high level of sequence variation in SLG alleles. Models for the evolution of SLG/SRK are presented.

P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity

The MDR1 P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is a transmembrane ATPase efflux pump for various lipophilic compounds, including many anti-cancer drugs. mAb UIC2, reactive with the extracellular moiety of Pgp, inhibits Pgp-mediated efflux. UIC2 reactivity with Pgp was increased by the addition of several Pgp-transported compounds or ATP-depleting agents, and by mutational inactivation of both nucleotide-binding domains (NBDs) of Pgp. UIC2 binding to Pgp mutated in both NBDs was unaffected in the presence of Pgp transport substrates or in ATP-depleted cells, whereas the reactivities of the wild-type Pgp and Pgps mutated in a single NBD were increased by these treatments to the level of the double mutant. These results indicate the existence of different Pgp conformations associated with different stages of transport-associated ATP hydrolysis and suggest trapping in a transient conformation as a mechanism for antibody-mediated inhibition of Pgp.