Simple and robust synchrotron and laboratory solutions for high-resolution multimodal X-ray phase-based imaging

Edge illumination X-ray phase contrast imaging techniques are capable of quantitative retrieval of differential phase, absorption and X-ray scattering. We have recently developed a series of approaches enabling high-resolution implementations, both using synchrotron radiation and laboratory-based set-ups. Three-dimensional reconstruction of absorption, phase and dark-field can be achieved with a simple rotation of the sample. All these approaches share a common trait which consists in the use of an absorber that shapes the radiation field, in order to make the phase modulations introduced by the sample detectable. This enables a well-defined and high-contrast structuring of the radiation field as well as an accurate modelling of the effects that are related to the simultaneous use of a wide range of energies. Moreover, it can also be adapted for use with detectors featuring large pixel sizes, which could be desirable when a high detection efficiency is important

Development of a chemically defined medium and discovery of new mitogenic growth factors for mouse hepatocytes: Mitogenic effects of FGF1/2 and PDGF

Chemically defined serum-free media for rat hepatocytes have been useful in identifying EGFR ligands and HGF/MET signaling as direct mitogenic factors for rat hepatocytes. The absence of such media for mouse hepatocytes has prevented screening for discovery of such mitogens for mouse hepatocytes. We present results obtained by designing such a chemically defined medium for mouse hepatocytes and demonstrate that in addition to EGFR ligands and HGF, the growth factors FGF1 and FGF2 are also important mitogenic factors for mouse hepatocytes. Smaller mitogenic response was also noticed for PDGF AB. Mouse hepatocytes are more likely to enter into spontaneous proliferation in primary culture due to activation of cell cycle pathways resulting from collagenase perfusion. These results demonstrate unanticipated fundamental differences in growth biology of hepatocytes between the two rodent species. Copyright: © 2014 Reekie et al

How do Zimbabweans value health states?

Background Quality of life weights based on valuations of health states are often used in cost utility analysis and population health measures. This paper reports on an attempt to develop quality of life weights within the Zimbabwe context. Methods 2,384 residents in randomly selected small residential plots of land in a high-density suburb of Harare valued descriptors of 38 health states based on different combinations of the five domains of the EQ-5D (mobility, self-care, usual activities, pain or discomfort and anxiety or depression). The English version of the EQ-5D was used. The time trade-off method was used to determine the values, and 19,020 individual preferences for health states were analysed. A residual maximum likelihood linear mixed model was used to estimate a function for predicting the values of all possible combinations of levels on the five domains. The model was fit to a random subset of two-thirds of the observations, with the remaining observations reserved for analysis of predictive validity. The results were compared to a similar study undertaken in the United Kingdom. Results A credible model was developed to predict the values of states that were not valued directly. In the subset of observations reserved for validation, the mean absolute difference between predicted and observed values was 0.045. All domains of the EQ-5D were found to contribute significantly to the model, both at the moderate and severe levels. Severe pain was found to have the largest negative coefficient, followed by the inability to wash and dress oneself. Conclusion Despite a generally lower education level than their European counterparts, urban Zimbabweans appear to value health states in a consistent manner, and the determination of a global method of establishing quality of life weights may be feasible and valid. However, as the relative weightings of the different domains, although correlated, differed from the standard set of weights recommended by the EuroQol Group, the locally determined coefficients should be used within the Zimbabwean context

Digital Communication Technology: Does Offering a Choice of Modality Improve Medication Adherence and Outcomes in a Persistent Asthma Population?

Background: Use of digital communication technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at patient preference around mode of medication reminders used to improve and maintain asthma medication adherence. Objective: To determine if, in a population already receiving automated medication reminders, offering a choice for preferred mode of reminder (text, email, phone) would improve their adherence and asthma outcomes over a 1-year period. Methods: This was a pragmatic, randomized controlled trial conducted at Kaiser Permanente Colorado involving 7522 adult patients with persistent asthma. Study patients were randomized to receive usual care or their choice of medication reminder. Differences between the 2 groups in both medication adherence and asthma outcomes were then assessed over the following year. Results: Only 30% of those offered a choice of medication reminder modality responded by making a choice, with 52% preferring text messaging. There was less of a decrease in adherence rate over the 1-year period in those who made a choice regarding the mode of medication refill reminder. There was no difference in asthma outcomes between those who did make a choice compared with those who did not make a choice regarding the mode of medication refill reminder. Conclusion: In a patient population already receiving medication reminders, offering a choice about what type of technology-enabled asthma medication reminder patients wanted did not improve outcomes but did enable a subgroup to better maintain their medication adherence.Ye

Comparative historical sociology and the State : problems of method

Historical sociology can be understood both as a specific sub-field of sociology and as providing general conceptual underpinnings of the discipline, to the extent that it provides an understanding of the specificity of the modern state and the perceived emergence of modernity within Europe. The association of modernity with Europe (and with a European history limited to the self-identified boundaries of the continent) is commonplace and pervasive within the social sciences and humanities. What such an understanding fails to take into consideration, however, are the connections between Europe and the rest of the world that constitute the broader context for the emergence of what is understood to be the modern world and its institutions, such as the state and market. In this article, I suggest that integral to this misunderstanding, and its reproduction over time, is the methodology of comparative historical sociology as represented by ideal types. In contrast, I argue for ‘connected sociologies’ as a more appropriate way to understand our shared past and its continuing impact upon the present. I examine these issues in the context of historical sociological understandings of nation-state formation

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

BACKGROUND: The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity. METHODS: For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals. RESULTS: Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner. CONCLUSION: The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders

Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

<p>Abstract</p> <p>Background</p> <p>Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the <it>in vitro </it>skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm²of acyclovir 5% cream or penciclovir 1% cream.</p> <p>Methods</p> <p>After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips.</p> <p>Results</p> <p>Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells.</p> <p>Conclusion</p> <p>Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.</p

A Unique Radiation Scheme for the Treatment of High-Grade Non-Metastatic Soft Tissue Sarcoma: The Detroit Medical Center Experience

Purpose:This is the initial report on the utilization of combined photon irradiation followed by a neutron boost irradiation for the initial management of patients with high-grade non-metastatic soft tissue sarcoma (STS). We present data on local control, complications, disease-free survival and overall survival in patients at high risk for local relapse