A biphasic response to adenosine in the coronary vasculature of the K+-arrested perfused rat heart

Biphasic vasodilatory responses to adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) were observed in the coronary vasculature of K(+)-arrested perfused rat hearts. Dose-response data for both agonists were best represented by two-site models. For adenosine, two sites with negative log ED50 (pED50) values of 8.1 +/- 0.1 (mean +/- S.E.M) and 5.2 +/- 0.1 were obtained, mediating 31 +/- 2% and 69 +/- 2% of the total response. In the presence of 8-phenyltheophylline, the vasodilatory response to adenosine remained best fitted to a two-site model with pED50 values of 7.0 +/- 0.2 and 5.4 +/- 0.2. The relative contribution of each site to the total response remained unchanged. For NECA, pED50 values of 9.6 +/- 0.1 and 6.8 +/- 0.2 were obtained, representing 48 +/- 3% and 52 +/- 3% of the sites, respectively. In contrast, ATP produced a monophasic response with a pED50 value of 8.8 +/- 0.1. These results provide evidence of adenosine receptor and response heterogeneity in the in situ coronary vasculature.

Ecosystem management along ephemeral rivers: Trading off socio-economic water supply and vegetation conservation under flood regime uncertainty

In ecosystems driven by water availability, plant community dynamics depend on complex interactions between vegetation, hydrology, and human water resources use. Along ephemeral rivers—where water availability is erratic—vegetation and people are particularly vulnerable to changes in each other's water use. Sensible management requires that water supply be maintained for people, while preserving ecosystem health. Meeting such requirements is challenging because of the unpredictable water availability. We applied information gap decision theory to an ecohydrological system model of the Kuiseb River environment in Namibia. Our aim was to identify the robustness of ecosystem and water management strategies to uncertainties in future flood regimes along ephemeral rivers. We evaluated the trade-offs between alternative performance criteria and their robustness to uncertainty to account for both (i) human demands for water supply and (ii) reducing the risk of species extinction caused by water mining. Increasing uncertainty of flood regime parameters reduced the performance under both objectives. Remarkably, the ecological objective (species coexistence) was more sensitive to uncertainty than the water supply objective. However, within each objective, the relative performance of different management strategies was insensitive to uncertainty. The ‘best’ management strategy was one that is tuned to the competitive species interactions in the Kuiseb environment. It regulates the biomass of the strongest competitor and, thus, at the same time decreases transpiration, thereby increasing groundwater storage and reducing pressure on less dominant species. This robust mutually acceptable strategy enables species persistence without markedly reducing the water supply for humans. This study emphasises the utility of ecohydrological models for resource management of water-controlled ecosystems. Although trade-offs were identified between alternative performance criteria and their robustness to uncertain future flood regimes, management strategies were identified that help to secure an ecologically sustainable water supply.

Sensitive aunt provotype

The Sensitive Aunt Provotype was designed as part of Indoor Climate, a three-year research study of participatory design and user-driven innovation. It resulted from collaboration between two universities and five industry partners. Indoor Climate sought to understand experiences of comfort in domestic, business and institutional environments. This involved a literature review on the meaning of comfort, an ethnographic study of indoor environments, a provotyping process designed to provoke debate, and the design development of new products. A provotype is a provocative prototype. The title of the work Sensitive Aunt was derived from an analogy by one of the project partners and the colours emitted by the device represent the temperature, light intensity and air quality of the environment in which it is placed. In addition, the LED screen suggests actions to improve the indoor climate. The sensitive aunt provotype was designed to provoke conversation around different conceptions of a new product or service from the perspectives of manufacturers and design users. While both speculative design and provotypes inspire debate, speculative design focuses on the normative protocols of design industries while provotypes trigger discussion with the industry partners. Critically challenging ideas such as 21 degrees is the temperature in which people should be comfortable, provotypes combine participation and provocation and open up design to issues of refocus on usability and values.

Online counselling in secondary schools: Would students seek help by this medium?

Students in secondary schools experience problems that can impact on their well-being and educational outcomes. Although face-to-face counselling is available in most Australian secondary schools, many students, particularly boys, do not seek appropriate help. Research suggests that online counselling can be effective and increase engagement. This study of 215 secondary school students sought to assess students' intention to use online counselling if it was made available in schools. The results found no gender difference in the likely intentions to seek online help though year level was significant and students experiencing psychological distress had a preference for online counselling. If students did use online counselling it was more likely they would discuss sensitive topics rather than for career issues. Implications for school counselling are discussed.

Drug accumulation into single drug-sensitive and drug-resistant prostate cancer cells conducted on the single cell bioanalyzer

Multidrug resistance (MDR) occurs in prostate cancer, and this happens when the cancer cells resist chemotherapeutic drugs by pumping them out of the cells. MDR inhibitors such as cyclosporin A (CsA) can stop the pumping and enhance the drugs accumulated in the cells. The cellular drug accumulation is monitored using a microfluidic chip mounted on a single cell bioanalyzer. This equipment has been developed to measure accumulation of drugs such as doxorubicin (DOX) and fluorescently labeled paclitaxel (PTX) in single prostate cancer cells. The inhibition of drug efflux on the same prostate cell was examined in drug-sensitive and drug-resistant cells. Accumulation of these drug molecules was not found in the MDR cells, PC-3 RX-DT2R cells. Enhanced drug accumulation was observed only after treating the MDR cell in the presence of 5 μM of CsA as the MDR inhibitor. We envision this monitoring of the accumulation of fluorescent molecules (drug or fluorescent molecules), if conducted on single patient cancer cells, can provide information for clinical monitoring of patients undergoing chemotherapy in the future.

Web crippling tests of cold-formed steel channels under two flange load cases

Cold-formed steel members have many advantages over hot-rolled steel members. However, they are susceptible to various buckling modes at stresses below the yield stress of the member because of their relatively high width-to-thickness ratio. Web crippling is a form of localized failure mode that can occur when the members are subjected to transverse high concentrated loadings and/or reactions. The four common loading conditions are the end-one-flange (EOF), interior-one-flange (IOF), end-two-flange (ETF) and interior-two-flange (ITF) loadings. Recently a test method has been proposed by AISI to obtain the web crippling capacities under these four loading conditions. Using this test method 42 tests were conducted in this research to investigate the web crippling behaviour and strengths of unlipped channels with stocky webs under ETF and ITF cases. DuraGal sections having a nominal yield stress of 450 MPa were tested with different web slenderness and bearing lengths. The flanges of these channel sections were not fastened to the supports. In this research the suitability of the currently available design rules for unlipped channels subject to web crippling was investigated, and suitable modifications were proposed where necessary. In addition to this, a new design rule was proposed based on the direct strength method to predict the web crippling capacities of tested beams. This paper presents the details of this experimental study and the results.

A homogeneous surface-enhanced Raman scattering platform for ultra-trace detection of trinitrotoluene in the environment

A facile and sensitive surface-enhanced Raman scattering substrate was prepared by controlled potentiostatic deposition of a closely packed single layer of gold nanostructures (AuNS) over a flat gold (pAu) platform. The nanometer scale inter-particle distance between the particles resulted in high population of ‘hot spots’ which enormously enhanced the scattered Raman photons. A renewed methodology was followed to precisely quantify the SERS substrate enhancement factor (SSEF) and it was estimated to be (2.2 ± 0.17) × 105. The reproducibility of the SERS signal acquired by the developed substrate was tested by establishing the relative standard deviation (RSD) of 150 repeated measurements from various locations on the substrate surface. A low RSD of 4.37 confirmed the homogeneity of the developed substrate. The sensitivity of pAu/AuNS was proven by determining 100 fM 2,4,6-trinitrotoluene (TNT) comfortably. As a proof of concept on the potential of the new pAu/AuNS substrate in field analysis, TNT in soil and water matrices was selectively detected after forming a Meisenheimer complex with cysteamine.

Rapid detection of TNT in aqueous media by selective label free surface enhanced Raman spectroscopy

We report rapid and ultra-sensitive detection system for 2,4,6-trinitrotoluene (TNT) using unmodified gold nanoparticles and surface-enhanced Raman spectroscopy (SERS). First, Meisenheimer complex has been formed in aqueous solution between TNT and cysteamine in less than 15 min of mixing. The complex formation is confirmed by the development of a pink colour and a new UV–vis absorption band around 520 nm. Second, the developed Meisenheimer complex is spontaneously self-assembled onto unmodified gold nanoparticles through a stable Au–S bond between the cysteamine moiety and the gold surface. The developed mono layer of cysteamine-TNT is then screened by SERS to detect and quantify TNT. Our experimental results demonstrate that the SERS-based assay provide an ultra-sensitive approach for the detection of TNT down to 22.7 ng/L. The unambiguous fingerprint identification of TNT by SERS represents a key advantage for our proposed method. The new method provides high selectivity towards TNT over 2,4 DNT and picric acid. Therefore it satisfies the practical requirements for the rapid screening of TNT in real life samples where the interim 24-h average allowable concentration of TNT in waste water is 0.04 mg/L.

Customer-driven innovation: Digital channels and community

This study investigates the role of digital channels in community-led businesses by exploring two case study companies, Uber and Airbnb. At present, these community-led businesses are disrupting traditional industries by connecting with customers via digital channels and facilitating transactions between two parties. A deductive structured qualitative content analysis approach utilising a predetermined categorization matrix was implemented to decipher the digital channels used by both companies. The results discovered that both company’s digital channels push the customer to their core channel, allowing, customers to create their own physical, largely self-governed communities. However, little research exists which explores and analyses the role of digital channels in forming community-led businesses. Therefore, this paper aims to instigate future research and discussion in this emerging area by concluding with future research agendas.

The role of design in the future of digital channels: Conceptual insights and future research directions

Purpose In the past channel literature has looked to other disciplines in developing and refining their theories, models and methods in order to evolve the field. This paper traces such history and highlights the substantial changes caused by the digital age. In light of this, the inclusion of design theory into future channel management is presented to overcome existing concerns. Design/methodology/approach A comprehensive review of literature on the history of channels, the emotional experience (people), limitations of digital innovation (technology) and the role of design (business) has been conducted to create a new approach, built upon the theory of the techno-economic innovation model. Findings The findings of this study propose design-led channel management as a new research area, providing novel research questions and future research directions. The inclusion of design and emotion theories indicates that the future of digital channel design requires a deeper understanding of customers and needs to go beyond technological advances. Theoretical implications The findings provide an opportunity to explore dynamic theories and methodologies within the field of design that will broaden the horizons and challenge existing notions in channel literature. Originality/value This paper is the first paper that introduces the theory of Emotionate, as the next evolution of channel literature. The value of Emotionate lies in providing a new design-led process of integrating emotion to provide advice to practitioners as well as identifies research areas for academia, thereby extending the reach and richness of this emerging research field.

Nurses' accountability for stroke quality of care: part one: Review of the literature on nursing-sensitive patient outcomes

Over the past decade, an exciting area of research has emerged that demonstrates strong links between specific nursing care activities and patient outcomes. This body of research has resulted in the identification of a set of "nursing-sensitive outcomes"(NSOs). These NSOs may be interpreted with more meaning when they are linked to evidence-based best practice guidelines, which provide a structured means of ensuring care is consistent among all health care team members, across geographic locations, and across care settings. Uptake of evidence-based best practices at the point of care has been shown to have a measurable positive impact on processes of care and patient outcomes. The purpose of this paper is to present a systematic, narrative review of the literature regarding the clinical effectiveness of nursing management strategies on stroke patient outcomes sensitive to nursing interventions. Subsequent investigation will explore current applications of nursing-sensitive outcomes to patients with stroke, and identify and validate measurable NSOs within stroke care delivery.

Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ~88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLUvariant was associated with lower fractional anisotropy-a widely accepted measure of white matter integrity-in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.

Information-theoretic analysis of brain white matter fiber orientation distribution functions

We propose a new information-theoretic metric, the symmetric Kullback-Leibler divergence (sKL-divergence), to measure the difference between two water diffusivity profiles in high angular resolution diffusion imaging (HARDI). Water diffusivity profiles are modeled as probability density functions on the unit sphere, and the sKL-divergence is computed from a spherical harmonic series, which greatly reduces computational complexity. Adjustment of the orientation of diffusivity functions is essential when the image is being warped, so we propose a fast algorithm to determine the principal direction of diffusivity functions using principal component analysis (PCA). We compare sKL-divergence with other inner-product based cost functions using synthetic samples and real HARDI data, and show that the sKL-divergence is highly sensitive in detecting small differences between two diffusivity profiles and therefore shows promise for applications in the nonlinear registration and multisubject statistical analysis of HARDI data.

Fluid registration of diffusion tensor images using information theory

We apply an information-theoretic cost metric, the symmetrized Kullback-Leibler (sKL) divergence, or $J$-divergence, to fluid registration of diffusion tensor images. The difference between diffusion tensors is quantified based on the sKL-divergence of their associated probability density functions (PDFs). Three-dimensional DTI data from 34 subjects were fluidly registered to an optimized target image. To allow large image deformations but preserve image topology, we regularized the flow with a large-deformation diffeomorphic mapping based on the kinematics of a Navier-Stokes fluid. A driving force was developed to minimize the $J$-divergence between the deforming source and target diffusion functions, while reorienting the flowing tensors to preserve fiber topography. In initial experiments, we showed that the sKL-divergence based on full diffusion PDFs is adaptable to higher-order diffusion models, such as high angular resolution diffusion imaging (HARDI). The sKL-divergence was sensitive to subtle differences between two diffusivity profiles, showing promise for nonlinear registration applications and multisubject statistical analysis of HARDI data.