Diffusion-weighted MR imaging of native and transplanted kidneys

Applications of diffusion-weighted (DW) magnetic resonance (MR) imaging outside the brain have gained increasing importance in recent years. Owing to technical improvements in MR imaging units and faster sequences, the need for noninvasive imaging without contrast medium administration, mainly in patients with renal insufficiency, can be met successfully by applying this technique. DW MR imaging is quantified by the apparent diffusion coefficient (ADC), which provides information on diffusion and perfusion simultaneously. By using a biexponential fitting process of the DW MR imaging data, these two entities can be separated, because this type of fitting process can serve as an estimate of both the perfusion fraction and the true diffusion coefficient. DW MR imaging can be applied for functional evaluation of the kidneys in patients with acute or chronic renal failure. Impairment of renal function is accompanied by a decreased ADC. Acute ureteral obstruction leads to perfusion and diffusion changes in the affected kidney, and renal artery stenosis results in a decreased ADC. In patients with pyelonephritis, diffuse or focal changes in signal intensity are seen on the high-b-value images, with increased signal intensity corresponding to low signal intensity on the ADC map. The feasibility and reproducibility of DW MR imaging in patients with transplanted kidneys have already been demonstrated, and initial results seem to be promising for the assessment of allograft deterioration. Overall, performance of renal DW MR imaging, presuming that measurements are of high quality, will further boost this modality, particularly for early detection of diffuse renal conditions, as well as more accurate characterization of focal renal lesions.

A MICROFLUIDIC METHOD TO MEASURE DIFFUSION IN HYDROGELS

A novel microfluidic method is proposed for studying diffusion of small molecules in a hydrogel. Microfluidic devices were prepared with semi-permeable microchannels defined by crosslinked poly(ethylene glycol) (PEG). Uptake of dye molecules from aqueous solutions flowing through the microchannels was observedoptically and diffusion of the dye into the hydrogel was quantified. To complement the diffusion measurements from the microfluidic studies, nuclear magnetic resonance(NMR) characterization of the diffusion of dye in the PEG hydrogels was performed. The diffusion of small molecules in a hydrogel is relevant to applications such asdrug delivery and modeling transport for tissue-engineering applications. The diffusion of small molecules in a hydrogel is dependent on the extent of crosslinking within the gel, gel structure, and interactions between the diffusive species and the hydrogel network. These effects were studied in a model environment (semi-infinite slab) at the hydrogelfluid boundary in a microfluidic device. The microfluidic devices containing PEG microchannels were fabricated using photolithography. The unsteady diffusion of small molecules (dyes) within the microfluidic device was monitored and recorded using a digital microscope. The information was analyzed with techniques drawn from digital microscopy and image analysis to obtain concentration profiles with time. Using a diffusion model to fit this concentration vs. position data, a diffusion coefficient was obtained. This diffusion coefficient was compared to those from complementary NMR analysis. A pulsed field gradient (PFG) method was used to investigate and quantify small molecule diffusion in gradient (PFG) method was used to investigate and quantify small molecule diffusion in hydrogels. There is good agreement between the diffusion coefficients obtained from the microfluidic methods and those found from the NMR studies. The microfluidic approachused in this research enables the study of diffusion at length scales that approach those of vasculature, facilitating models for studying drug elution from hydrogels in blood-contacting applications.

Diffusion of contrast medium after perineural injection of the palmar nerves: an in vivo and in vitro study

REASONS FOR PERFORMING STUDY: Proximal diffusion of local anaesthetic solution after perineural anaesthesia may lead to the desensitisation of structures other than those intended. However, there is no evidence-based study demonstrating the potential distribution and diffusion of local anaesthetic solution after perineural analgesia in the distal limb. OBJECTIVE: To document the potential diffusion of local anaesthetic solution using a radiopaque contrast model and to evaluate the influence of walking compared with confinement in a stable after injection. METHODS: Radiopaque contrast medium was injected subcutaneously over one palmar nerve at the base of the proximal sesamoid bones in 6 nonlame mature horses. Horses were assigned randomly to stand still or walk after injection. Radiographs were obtained 0, 5, 10, 15, 20 and 30 min after injection and were analysed to determine the distribution and diffusion of the contrast medium. RESULTS: In 89% of injections an elongated pattern of the contrast medium was observed suggesting distribution along the neurovascular bundle. After 49% of injections a fine radiopaque line extended proximally from the contrast 'patch', and in 25% of injections a line extended distally. There was significant proximal and distal diffusion with time when sequential radiographs of each limb were compared. The greatest diffusion occurred in the first 10 min. Walking did not significantly influence the extent of either proximal or distal diffusion. CONCLUSIONS AND POTENTIAL RELEVANCE: Significant proximal diffusion occurs in the first 10 min after perineural injection in the distal aspect of the limb and should be considered when interpreting nerve blocks. Distribution of local anaesthetic solution outside the fascia surrounding the neurovascular bundle or in lymphatic vessels may explain delayed or decreased effects.

Climate change and infectious diseases of wildlife: Altered interactions between pathogens, vectors and hosts

Infectious diseases result from the interactions of host, pathogens, and, in the case of vector-borne diseases, also vectors. The interactions involve physiological and ecological mechanisms and they have evolved under a given set of environmental conditions. Environmental change, therefore, will alter host-pathogen-vector interactions and, consequently, the distribution, intensity, and dynamics of infectious diseases. Here, we review how climate change may impact infectious diseases of aquatic and terrestrial wildlife. Climate change can have direct impacts on distribution, life cycle, and physiological status of hosts, pathogens and vectors. While a change in either host, pathogen or vector does not necessarily translate into an alteration of the disease, it is the impact of climate change on the interactions between the disease components which is particularly critical for altered disease risks. Finally, climate factors can modulate disease through modifying the ecological networks host-pathogen-vector systems are belonging to, and climate change can combine with other environmental stressors to induce cumulative effects on infectious diseases. Overall, the influence of climate change on infectious diseases involves different mechanisms, it can be modulated by phenotypic acclimation and/or genotypic adaptation, it depends on the ecological context of the host-pathogen-vector interactions, and it can be modulated by impacts of other stressors. As a consequence of this complexity, non-linear responses of disease systems under climate change are to be expected. To improve predictions on climate change impacts on infectious disease, we suggest that more emphasis should be given to the integration of biomedical and ecological research for studying both the physiological and ecological mechanisms which mediate climate change impacts on disease, and to the development of harmonized methods and approaches to obtain more comparable results, as this would support the discrimination of case-specific versus general mechanisms

Expressing and Amplifying Positive Emotions Facilitate Goal Attainment in Workplace Interactions

Expressing emotions has social functions; it provides information, affects social interactions, and shapes relationships with others. Expressing positive emotions could be a strategic tool for improving goal attainment during social interactions at work. Such effects have been found in research on social contagion, impression management, and emotion work. However, expressing emotions one does not feel entails the risk of being perceived as inauthentic. This risk may well be worth taking when the emotions felt are negative, as expressing negative emotions usually has negative effects. When experiencing positive emotions, however, expressing them authentically promises benefits, and the advantage of amplifying them is not so obvious. We postulated that expressing, and amplifying, positive emotions would foster goal attainment in social interactions at work, particularly when dealing with superiors. Analyses are based on 494 interactions involving the pursuit of a goal by 113 employes. Multilevel analyses, including polynomial analyses, show that authentic display of positive emotions supported goal attainment throughout. However, amplifying felt positive emotions promoted goal attainment only in interactions with superiors, but not with colleagues. Results are discussed with regard to the importance of hierarchy for detecting, and interpreting, signs of strategic display of positive emotions.

Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

BACKGROUND The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS Experimental meningitis in rats was induced by intracisternal injection of live pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis. RESULTS Both ADC and the volume of hippocampus were significantly increased in meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001, Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats with an early onset bacteremia as compared to meningitis rats with attenuated bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no association was found between ADC or volume and the extent of apoptosis (p > 0.05). CONCLUSIONS In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

Probing the effect of minor groove interactions on the catalytic efficiency of DNAzymes 8–17 and 10–23

DNAzymes (Dz) 8–17 and 10–23 are two widely studied and well-characterized RNA-cleaving DNA catalysts. In an effort to further improve the understanding of the fragile interactions and dynamics of the enzymatic mechanism, this study examines the catalytic efficiency of minimally modified DNAzymes. Five single mutants of Dz8–17 and Dz10–23 were prepared by replacing the adenine residues in the corresponding catalytic cores with 3-deazaadenine units. Kinetic assays were used to assess the effect on the catalytic activity and thereby identify the importance of hydrogen bonding that arises from the N3 atoms. The results suggest that modifications at A15 and A15.0 of Dz8–17 have a significant influence and show a reduction in catalytic activity. Modification at each location in Dz10–23 results in a decrease of the observed rate constants, with A12 appearing to be the most affected with a reduction of ∼80% of kobs and ∼25% of the maximal cleavage rate compared to the wild-type DNAzyme. On the other hand, modification of A12 in Dz8–17 showed an ∼130% increase in kobs, thus unraveling a new potential site for the introduction of chemical modifications. A pH-profile analysis showed that the chemical cleavage step is rate-determining, regardless of the presence and/or location of the mutation. These findings point towards the importance of the N3-nitrogens of certain adenine nucleotides located within the catalytic cores of the DNAzymes for efficient catalytic activity and further suggest that they might directly partake in maintaining the appropriate tertiary structure. Therefore, it appears that minor groove interactions constitute an important feature of DNAzymes as well as ribozymes.

Disentangling mental imagery and perceptual expectation

Mental imagery and perception are thought to rely on similar neural circuits, and many recent behavioral studies have attempted to demonstrate interactions between actual physical stimulation and sensory imagery in the corresponding sensory modality. However, there has been a lack of theoretical understanding of the nature of these interactions, and both interferential and facilitatory effects have been found. Facilitatory effects appear strikingly similar to those that arise due to experimental manipulations of expectation. Using a self-motion discrimination task, we try to disentangle the effects of mental imagery from those of expectation by using a hierarchical drift diffusion model to investigate both choice data and response times. Manipulations of expectation are reasonably well understood in terms of their selective influence on parameters of the drift diffusion model, and in this study, we make the first attempt to similarly characterize the effects of mental imagery. We investigate mental imagery within the computational framework of control theory and state estimation. • Mental imagery and perception are thought to rely on similar neural circuits; however, on more theoretical grounds, imagery seems to be closely related to the output of forward models (sensory predictions). • We reanalyzed data from a study of imagined self-motion. • Bayesian modeling of response times may allow us to disentangle the effects of mental imagery on behavior from other cognitive (top-down) effects, such as expectation.

MRI texture analysis as means for addressing rehydration and milk diffusion of cereals

Cereals microstructure is one of the primary quality attributes of cereals. Cereals rehydration and milk diffusion depends on such microstructure and thus, the crispiness and the texture, which will make it more palatable for the final consumer. Magnetic Resonance Imaging (MRI) is a very powerful topographic tool since acquisition parameter leads to a wide possibility for identifying textures, structures and liquids mobility. It is suited for non-invasive imaging of water and fats. Rehydration and diffusion cereals processes were measured by MRI at different times and using two different kinds of milk, varying their fat level. Several images were obtained. A combination of textural analysis (based on the analysis of histograms) and segmentation methods (in order to understand the rehydration level of each variety of cereals) were performed. According to the rehydration level, no advisable clustering behavior was found. Nevertheless, some differences were noticeable between the coating, the type of milk and the variety of cereals

Learning Analytics and Interactions in Virtual Learning Environments. A Comparative Study of Typologies and their Relationship with Academic Performance

Analysis of learning data (learning analytics) is a new research field with high growth potential. The main objective of Learning analytics is the analysis of data (interactions being the basic data unit) generated in virtual learning environments, in order to maximize the outcomes of the learning process; however, a consensus has not been reached yet on which interactions must be measured and what is their influence on learning outcomes. This research is grounded on the study of e-learning interaction typologies and their relationship with students? academic performance, by means of a comparative study between different interaction typologies (based on the agents involved, frequency of use and participation mode). The main conclusions are a) that classifications based on agents offer a better explanation of academic performance; and b) that each of the three typologies are able to explain academic performance in terms of some of their components (student-teacher and student-student interactions, evaluating students interactions and active interactions, respectively), with the other components being nonrelevant.

Cell Cycle–regulated Transcription in Fission Yeast: Cdc10–Res Protein Interactions during the Cell Cycle and Domains Required for Regulated Transcription

In Schizosaccharomyces pombe the MBF (DSC1) complex mediates transcriptional activation at Start and is composed of a common subunit called Cdc10 in combination with two alternative DNA-binding partners, Res1 and Res2. It has been suggested that a high-activity MBF complex (at G1/S) is switched to a low-activity complex (in G2) by the incorporation of the negative regulatory subunit Res2. We have analyzed MBF protein–protein interactions and find that both Res proteins are associated with Cdc10 throughout the cell cycle, arguing against this model. Furthermore we demonstrate that Res2 is capable of interacting with a mutant form of Cdc10 that has high transcriptional activity. It has been shown previously that both Res proteins are required for periodic cell cycle–regulated transcription. Therefore a series of Res1–Res2 hybrid molecules was used to determine the domains that are specifically required to regulate periodic transcription. In Res2 the nature of the C-terminal region is critical, and in both Res1 and Res2, a domain overlapping the N-terminal ankyrin repeat and a recently identified activation domain is important for mediating cell cycle–regulated transcription.

“Coarse” stability and bifurcation analysis using time-steppers: A reaction-diffusion example

Evolutionary, pattern forming partial differential equations (PDEs) are often derived as limiting descriptions of microscopic, kinetic theory-based models of molecular processes (e.g., reaction and diffusion). The PDE dynamic behavior can be probed through direct simulation (time integration) or, more systematically, through stability/bifurcation calculations; time-stepper-based approaches, like the Recursive Projection Method [Shroff, G. M. & Keller, H. B. (1993) SIAM J. Numer. Anal. 30, 1099–1120] provide an attractive framework for the latter. We demonstrate an adaptation of this approach that allows for a direct, effective (“coarse”) bifurcation analysis of microscopic, kinetic-based models; this is illustrated through a comparative study of the FitzHugh-Nagumo PDE and of a corresponding Lattice–Boltzmann model.

Architectural Technology and the BIM Acronym 3: Getting to Grips with BIM

Among Small and Medium Sized Enterprises (SMEs) in particular, the UK Government’s ambitions regarding BIM uptake and diffusion across the construction sector may be tempered by a realpolitik shaped in part by interactions between the industry, Higher Education (HE) and professional practice. That premise also has a global perspective. Building on the previous 2 papers, Architectural technology and the BIM Acronym 1 and 2, this third iteration is a synthesis of research and investigations carried out over a number of years directly related to the practical implementation of BIM and its impact upon BE SMEs. First challenges, risks and potential benefits for SMEs and micros in facing up to the necessity to engage with digital tools in a competitive and volatile marketplace are discussed including tailoring BIM to suit business models, and filtering out achievable BIM outcomes from generic and bespoke aspects of practice. Second the focus is on setting up and managing teams engaging with BIM scenarios, including the role of clients; addresses a range of paradigms including lonely BIM and collaborative working. The significance of taking a whole life view with BIM is investigated including embedding soft landings principles into project planning and realisation. Thirdly procedures for setting up and managing common data environments are identified and the value of achieving smooth information flow is addressed. The overall objective of this paper is to provide SMEs with a practical strategy to develop a toolkit to BIM implementation.

Technology diffusion, services, and endogenous growth in Europe. Is the Lisbon Strategy still alive? Bruges European Economic Research (BEER) Papers 2/May 2005

We explore the role of business services in knowledge accumulation and growth and the determinants of knowledge diffusion including the role of distance. A continuous time model is estimated on several European countries, Japan, and the US. Policy simulations illustrate the benefits for EU growth of the deepening of the single market, the reduction of regulatory barriers, and the accumulation of technology and human capital. Our results support the basic insights of the Lisbon Agenda. Economic growth in Europe is enhanced to the extent that: trade in services increases, technology accumulation and diffusion increase, regulation becomes both less intensive and more uniform across countries, and human capital accumulation increases in all countries.

Lung Structure and the Intrinsic Challenges of Gas Exchange

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints. © 2016 American Physiological Society. Compr Physiol 6:827-895, 2016.