Effect of drainage and wildfire on peat hydrophysical properties

Consecutive multiple disturbances to northern peatlands can dramatically impact peat hydrophysical properties. We examine the impact of a double disturbance (drainage and wildfire) on the hydrophysical and moisture retention properties of peat, a key regulator of peatland ecohydrological resilience, and compare this with the impact to each individual disturbance (drainage and wildfire). The compound effect of drainage and wildfire resulted in a shift of the surface datum down the peat profile, revealing denser peat. Less-dense near-surface peats that regulate water-table position and near-surface moisture content, both favourable to Sphagnum recolonization, were lost. At a drained peatland that was then subject to wildfire, peat bulk density increased by 14.1%, von Post humification class increased by two categories and water retention increased by 15.6%, compared with an adjacent burned but undrained (single disturbance) portion of the fen. We discuss the key hydrophysical metrics of peatland vulnerability and outline how they are affected by the isolated impacts of drainage and wildfire, as well as their combined effects. We demonstrate that multiple peatland disturbances have likely led to an increase in hydrological limitations to Sphagnum recovery, which may impact peatland ecohydrological resilience.

Normative modeling for personalized clinical pathway using organizational semiotics methods

Clinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length and cost of hospital stay. However, nowadays most of them are static and nonpersonalized. Our objective is to capture and represent clinical pathway using organizational semiotics method including Semantic Analysis which determines semantic units in clinical pathway, their relationship and their patterns of behavior, and Norm Analysis which extracts and specifies the norms that establish how and when these medical behaviors will occur. Finally, we propose a method to develop clinical pathway ontology based on the results of Semantic Analysis and Norm analysis. This approach will give a contribution to design personalized clinical pathway by defining a set of possible patterns of behavior and theClinical pathways are widely adopted by many large hospitals around the world in order to provide high-quality patient treatment and reduce the length and cost of hospital stay. However, nowadays most of them are static and nonpersonalized. Our objective is to capture and represent clinical pathway using organizational semiotics method including Semantic Analysis which determines semantic units in clinical pathway, their relationship and their patterns of behavior, and Norm Analysis which extracts and specifies the norms that establish how and when these medical behaviors will occur. Finally, we propose a method to develop clinical pathway ontology based on the results of Semantic Analysis and Norm analysis. This approach will give a contribution to design personalized clinical pathway by defining a set of possible patterns of behavior and the norms that govern the behavior based on patient’s condition.

Knowledge-based clinical pathway for medical quality improvement

Clinical pathways have been adopted for various diseases in clinical departments for quality improvement as a result of standardization of medical activities in treatment process. Using knowledge-based decision support on the basis of clinical pathways is a promising strategy to improve medical quality effectively. However, the clinical pathway knowledge has not been fully integrated into treatment process and thus cannot provide comprehensive support to the actual work practice. Therefore this paper proposes a knowledgebased clinical pathway management method which contributes to make use of clinical knowledge to support and optimize medical practice. We have developed a knowledgebased clinical pathway management system to demonstrate how the clinical pathway knowledge comprehensively supports the treatment process. The experiences from the use of this system show that the treatment quality can be effectively improved by the extracted and classified clinical pathway knowledge, seamless integration of patient-specific clinical pathway recommendations with medical tasks and the evaluating pathway deviations for optimization.

Integrated clinical pathway management for medical quality improvement-based on a semiotically inspired systems architecture

Clinical pathway is an approach to standardise care processes to support the implementations of clinical guidelines and protocols. It is designed to support the management of treatment processes including clinical and non-clinical activities, resources and also financial aspects. It provides detailed guidance for each stage in the management of a patient with the aim of improving the continuity and coordination of care across different disciplines and sectors. However, in the practical treatment process, the lack of knowledge sharing and information accuracy of paper-based clinical pathways burden health-care staff with a large amount of paper work. This will often result in medical errors, inefficient treatment process and thus poor quality medical services. This paper first presents a theoretical underpinning and a co-design research methodology for integrated pathway management by drawing input from organisational semiotics. An approach to integrated clinical pathway management is then proposed, which aims to embed pathway knowledge into treatment processes and existing hospital information systems. The capability of this approach has been demonstrated through the case study in one of the largest hospitals in China. The outcome reveals that medical quality can be improved significantly by the classified clinical pathway knowledge and seamless integration with hospital information systems.

Genetic association analysis of vitamin D pathway with obesity traits

Objective:Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study.Methods:We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865).Results:In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist-hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits.Conclusions:Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homestasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature.

Fold-change detection in a whole-pathway model of Escherichia coli chemotaxis

There has been recent interest in sensory systems that are able to display a response which is proportional to a fold change in stimulus concentration, a feature referred to as fold-change detection (FCD). Here, we demonstrate FCD in a recent whole-pathway mathematical model of Escherichia coli chemotaxis. FCD is shown to hold for each protein in the signalling cascade and to be robust to kinetic rate and protein concentration variation. Using a sensitivity analysis, we find that only variations in the number of receptors within a signalling team lead to the model not exhibiting FCD. We also discuss the ability of a cell with multiple receptor types to display FCD and explain how a particular receptor configuration may be used to elucidate the two experimentally determined regimes of FCD behaviour. All findings are discussed in respect of the experimental literature.

The trafficking pathway of a wheat storage protein in transgenic rice endosperm

Background and Aims The trafficking of proteins in the endoplasmic reticulum (ER) of plant cells is a topic of considerable interest since this organelle serves as an entry point for proteins destined for other organelles, as well as for the ER itself. In the current work, transgenic rice was used to study the pattern and pathway of deposition of the wheat high molecular weight (HMW) glutenin sub-unit (GS) 1Dx5 within the rice endosperm using specific antibodies to determine whether it is deposited in the same or different protein bodies from the rice storage proteins, and whether it is located in the same or separate phases within these. Methods The protein distribution and the expression pattern of HMW sub-unit 1Dx5 in transgenic rice endosperm at different stages of development were determined using light and electron microscopy after labelling with antibodies. Key results The use of HMW-GS-specific antibodies showed that sub-unit 1Dx5 was expressed mainly in the sub-aleurone cells of the endosperm and that it was deposited in both types of protein body present in the rice endosperm: derived from the ER and containing prolamins, and derived from the vacuole and containing glutelins. In addition, new types of protein bodies were also formed within the endosperm cells. Conclusions The results suggest that the HMW 1Dx5 protein could be trafficked by either the ER or vacuolar pathway, possibly depending on the stage of development, and that its accumulation in the rice endosperm could compromise the structural integrity of protein bodies and their segregation into two distinct populations in the mature endosperm.

A bifurcated pathway to thiazoles and imidazoles using a modular flow microreactor

A scalable method for the preparation of 4,5-disubstituted thiazoles and imidazoles as distinct regioisomeric products using a modular flow microreactor has been devised. The process makes use of microfluidic reaction chips and packed immobilized-reagent columns to effect bifurcation of the reaction pathway.

Climate change impacts in the design of drainage systems: case study of Portugal

This paper aims to assess the necessity of updating the intensity-duration-frequency (IDF) curves used in Portugal to design building storm-water drainage systems. A comparative analysis of the design was performed for the three predefined rainfall regions in Portugal using the IDF curves currently in use and estimated for future decades. Data for recent and future climate conditions simulated by a global and regional climate model chain are used to estimate possible changes of rainfall extremes and its implications for the drainage systems. The methodology includes the disaggregation of precipitation up to subhourly scales, the robust development of IDF curves, and the correction of model bias. Obtained results indicate that projected changes are largest for the plains in southern Portugal (5–33%) than for mountainous regions (3–9%) and that these trends are consistent with projected changes in the long-term 95th percentile of the daily precipitation throughout the 21st century. The authors conclude there is a need to review the current precipitation regime classification and change the new drainage systems towards larger dimensions to mitigate the projected changes in extreme precipitation.

Abrupt CO2 experiments as tools for predicting and understanding CMIP5 representative concentration pathway projections

A fast simple climate modelling approach is developed for predicting and helping to understand general circulation model (GCM) simulations. We show that the simple model reproduces the GCM results accurately, for global mean surface air temperature change and global-mean heat uptake projections from 9 GCMs in the fifth coupled model inter-comparison project (CMIP5). This implies that understanding gained from idealised CO2 step experiments is applicable to policy-relevant scenario projections. Our approach is conceptually simple. It works by using the climate response to a CO2 step change taken directly from a GCM experiment. With radiative forcing from non-CO2 constituents obtained by adapting the Forster and Taylor method, we use our method to estimate results for CMIP5 representative concentration pathway (RCP) experiments for cases not run by the GCMs. We estimate differences between pairs of RCPs rather than RCP anomalies relative to the pre-industrial state. This gives better results because it makes greater use of available GCM projections. The GCMs exhibit differences in radiative forcing, which we incorporate in the simple model. We analyse the thus-completed ensemble of RCP projections. The ensemble mean changes between 1986–2005 and 2080–2099 for global temperature (heat uptake) are, for RCP8.5: 3.8 K (2.3 × 1024 J); for RCP6.0: 2.3 K (1.6 × 1024 J); for RCP4.5: 2.0 K (1.6 × 1024 J); for RCP2.6: 1.1 K (1.3 × 1024 J). The relative spread (standard deviation/ensemble mean) for these scenarios is around 0.2 and 0.15 for temperature and heat uptake respectively. We quantify the relative effect of mitigation action, through reduced emissions, via the time-dependent ratios (change in RCPx)/(change in RCP8.5), using changes with respect to pre-industrial conditions. We find that the effects of mitigation on global-mean temperature change and heat uptake are very similar across these different GCMs.

Tityus discrepans scorpion venom activates platelets through GPVI and a novel Src-dependent signaling pathway

In humans and other mammals, Tityus discrepans (Td) scorpion envenomation produces a variety of systemic effects including respiratory distress, a generalized inflammatory reaction, modulation of blood pressure, fibrin formation, and platelet activation. For many of these effects, the venom components and underlying mechanisms are not known. In the present study, we demonstrate that Td venom (TdV) stimulates integrin αIIbβ3-dependent aggregation of washed human and mouse platelets downstream of Src kinase activation. The pattern of increase in tyrosine phosphorylation induced by TdV in human platelets is similar to that induced by the collagen receptor GPVI, and includes FcR γ-chain, Syk, and PLC γ 2. Confirmation of GPVI activation by TdV was achieved by expression of human GPVI in chicken DT40 B cells and use of a reporter assay. To our surprise, TdV was able to activate mouse platelets deficient in the GPVI-FcR γ-chain complex through a pathway that was also dependent on Src kinases. TdV therefore activates platelets through GPVI and a second, as yet unidentified Src kinase-dependent pathway.

Experimental evidence for proposed transformation pathway from the inverse hexagonal to inverse diamond cubic phase from oriented lipid samples

A macroscopically oriented inverse hexagonal phase (HII) of the lipid phytantriol in water is converted to an oriented inverse double diamond bicontinuous cubic phase (QIID). The initial HII phase is uniaxially oriented about the long axis of a capillary with the cylinders parallel to the capillary axis. The HII phase is converted by cooling to a QII D phase which is also highly oriented, where the cylindrical axis of the former phase has been converted to a ⟨110⟩ axis in the latter, as demonstrated by small-angle X-ray scattering. This epitaxial relationship allows us to discriminate between two competing proposed geometric pathways to convert HII to QIID. Our findings also suggest a new route to highly oriented cubic phase coatings, with applications as nanomaterial templates.