Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure

Postprandial hyperglycemia is implicated as a risk factor predisposing to vascular complications. This study was designed to assess recurrent short-term increases in glucose on markers of renal fibrogenesis. Human renal cortical fibroblasts were exposed to fluctuating short-term (2 h) increases to 15 mM D-glucose, three times a day over 72 h, on a background of 5 mM D-glucose. To determine whether observed changes were due to fluctuating osmolality, identical experiments were undertaken with cells exposed to L-glucose. Parallel experiments were performed in cells exposed to 5 mM D-glucose and constant exposure to either 15 or 7.5 mM D-glucose. Fluctuating D-glucose increased extracellular matrix, as measured by proline incorporation ( P < 0.05), collagen IV ( P < 0.005), and fibronectin production ( P < 0.001), in association with increased tissue inhibitor of matrix metalloproteinase (MMP) ( P < 0.05). Sustained exposure to 15 mM D-glucose increased fibronectin ( P < 0.001), in association with increased MMP-2 ( P = 0.01) and MMP-9 activity ( P < 0.05), suggestive of a protective effect on collagen matrix accumulation. Transforming growth factor-beta(1) (TGF-beta(1)) mRNA was increased after short-term (90 min) exposure to 15 mM glucose (P < 0.05) and after 24-h exposure to 7.5 mM ? ( P < 0.05). Normalization of TGF-beta(1) secretion occurred within 48 h of constant exposure to an elevated glucose. Fluctuating L-glucose also induced TGF-beta(1) mRNA and a profibrotic profile, however, to a lesser extent than observed with exposure to fluctuating D-glucose. The results suggest that exposure to fluctuating glucose concentrations increases renal interstitial fibrosis compared with stable elevations in D-glucose. The effects are, in part, due to the inherent osmotic changes.

Data methods in optometry Part 9: experimental design and analysis of variance

The key to the correct application of ANOVA is careful experimental design and matching the correct analysis to that design. The following points should therefore, be considered before designing any experiment: 1. In a single factor design, ensure that the factor is identified as a 'fixed' or 'random effect' factor. 2. In more complex designs, with more than one factor, there may be a mixture of fixed and random effect factors present, so ensure that each factor is clearly identified. 3. Where replicates can be grouped or blocked, the advantages of a randomised blocks design should be considered. There should be evidence, however, that blocking can sufficiently reduce the error variation to counter the loss of DF compared with a randomised design. 4. Where different treatments are applied sequentially to a patient, the advantages of a three-way design in which the different orders of the treatments are included as an 'effect' should be considered. 5. Combining different factors to make a more efficient experiment and to measure possible factor interactions should always be considered. 6. The effect of 'internal replication' should be taken into account in a factorial design in deciding the number of replications to be used. Where possible, each error term of the ANOVA should have at least 15 DF. 7. Consider carefully whether a particular factorial design can be considered to be a split-plot or a repeated measures design. If such a design is appropriate, consider how to continue the analysis bearing in mind the problem of using post hoc tests in this situation.

Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial

Background - Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings - We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions - Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.

The dynamics of global sourcing : perspectives and practices:6th global sourcing workshop 2012, Courchevel, France, March 12-15, 2012, revised selected papers

This edited book is intended for use by students, academics and practitioners who take interest in the outsourcing and offshoring of information technology and business services and processes. The book offers a review of the key topics in outsourcing and offshoring, populated with practical frameworks that serve as a tool kit for practitioners, academics and students. The range of topics covered in this book is wide and diverse, and represents both client and supplier perspectives on sourcing of global services. Various aspects related to the decision making process (e.g., asset transfer), learning mechanisms and organizational practices for managing outsourcing relationships are discussed in great depth. Contemporary sourcing models, including cloud services, are examined. Client dependency on the outsourcing provider, and social aspects, such as identity, are discussed in detail. Furthermore, resistance in outsourcing and failures are investigated to derive lessons as to how to avoid them and improve efficiency in outsourcing. Topics discussed in this book combine theoretical and practical insights regarding challenges that both clients and vendors face. Case studies from client and vendor organizations are used extensively throughout the book. Last but not least, the book examines current and future trends in outsourcing and offshoring, placing particular attention on the centrality of innovation in sourcing arrangements, and how innovation can be realized in outsourcing. The book is based on a vast empirical base brought together through years of extensive research by leading researchers in information systems, strategic management and operations.

Hierarchical macroporous-mesoporous SBA-15 sulfonic acid catalysts for biodiesel synthesis

Hierarchical macroporous-mesoporous SBA-15 silicas have been synthesised via dual-templating routes employing liquid crystalline surfactants and polystyrene beads. These offer high surface areas and well-defined, interconnecting macro- and mesopore networks with respective narrow size distributions around 300 nm and 3-5 nm for polystyrene:tetraethoxysilane ratios ≥2:1. Subsequent functionalisation with propylsulfonic acid yields the first organized, macro-mesoporous solid acid catalyst. The enhanced mass transport properties of these new bi-modal solid acid architectures confer significant rate enhancements in the transesterification of bulky glyceryl trioctanoate, and esterification of long chain palmitic acid, over pure mesoporous analogues. This paves the way to the wider application of hierarchical catalysts in biofuel synthesis and biomass conversion. © 2010 The Royal Society of Chemistry.

Tunable KIT-6 mesoporous sulfonic acid catalysts for fatty acid esterification

We report the first catalytic application of pore-expanded KIT-6 propylsulfonic acid (PrSO H) silicas, in fatty acid esterification with methanol under mild conditions. As-synthesized PrSO H-KIT-6 exhibits a 40 and 70% enhancement in turnover frequency (TOF) toward propanoic and hexanoic acid esterification, respectively, over a PrSO H-SBA-15 analogue of similar 5 nm pore diameter, reflecting the improved mesopore interconnectivity of KIT-6 over SBA-15. However, pore accessibility becomes rate-limiting in the esterification of longer chain lauric and palmitic acids over both solid acid catalysts. This problem can be overcome via hydrothermal aging protocols which permit expansion of the KIT-6 mesopore to 7 nm, thereby doubling the TOF for lauric and palmitic acid esterification over that achievable with PrSO H-SBA-15. © 2012 American Chemical Society.

Pore-expanded SBA-15 sulfonic acid silicas for biodiesel synthesis

Here we present the first application of pore-expanded SBA-15 in heterogeneous catalysis. Pore expansion over the range 6-14 nm confers a striking activity enhancement towards fatty acid methyl ester (FAME) synthesis from triglycerides (TAG), and free fatty acid (FFA), attributed to improved mass transport and acid site accessibility.

International education and the post-9/11 syndrome: A study of international educators in selected Miami-area colleges

This dissertation investigated the relationship between the September 11, 2001 terrorist attacks and the internationalization agenda of U.S. colleges and universities. The construct, post-9/11 syndrome, is used metaphorically to delineate the apparent state of panic and disequilibrium that followed the incident. Three research questions were investigated, with two universities in the Miami-area of South Florida, one private and the other public, as qualitative case studies. The questions are: (a) How are international student advisors and administrators across two types of institutions dealing with the post-9/11 syndrome? (b) What, if any, are the differences in international education after 9/11? (c) What have been the institutional priorities in relation to international education before and after 9/11? Data-gathering methods included interviews with international student/study abroad advisors and administrators with at least 8 years of experience in the function(s) at their institutions, document and institutional data analysis. The interviews were based on the three-part scheme developed by Schuman (1982): context of experience, details of experience and reflection on the meaning of experiences. Taped interviews, researcher insights, and member checks of transcripts constituted an audit trail for this study. Key findings included a progressive decline in Fall to Fall enrollment of international students at UM by 13.05% in the 5 years after 9/11, and by 6.15% at FIU in the seven post-9/11 years. In both institutions, there was an upsurge in interest in study abroad during the same period but less than 5% of enrolled students ventured abroad annually. I summarized the themes associated with the post-9/11 environment of international education as perceived by my participants at both institutions as 3Ms, 3Ts, and 1D: Menace of Anxiety and Fear, Menace of Insularity and Insecurity, Menace of Over-Regulation and Bigotry, Trajectory of Opportunity, Trajectory of Contradictions, Trajectory of Illusion, Fatalism and Futility, and Dominance of Technology. Based on these findings, I recommended an integrated Internationalization At Home Plus Collaborative Outreach (IAHPCO) approach to internationalization that is based on a post-9/11 recalibration of national security and international education as complementary rather than diametrically opposed concepts.

FTIR-inferred biogeochemical properties for the past 3.6 Myr in the sediment record of core ICDP5011-1 in Lake Elgygytgyn, NE Russia

A number of studies have shown that Fourier transform infrared spectroscopy (FTIR) can be applied to quantitatively assess lacustrine sediment constituents. In this study, we developed calibration models based on FTIR for the quantitative determination of biogenic silica (BSi; n = 420; gradient: 0.9-56.5%), total organic carbon (TOC; n = 309; gradient: 0-2.9%), and total inorganic carbon (TIC; n= 152; gradient: 0-0.4%) in a 318 m-long sediment record with a basal age of 3.6 million years from Lake El'gygytgyn, Far East Russian Arctic. The developed partial least squares (PLS) regression models yield high cross-validated (CV) R2CV = 0.86-0.91 and low root mean square error of cross-validation (RMSECV) (3.1-7.0% of the gradient for the different properties). By applying these models to 6771 samples from the entire sediment record, we obtained detailed insight into bioproductivity variations in Lake El'gygytgyn throughout the middle to late Pliocene and Quaternary. High accumulation rates of BSi indicate a productivity maximum during the middle Pliocene (3.6-3.3 Ma), followed by gradually decreasing rates during the late Pliocene and Quaternary. The average BSi accumulation during the middle Pliocene was ~3 times higher than maximum accumulation rates during the past 1.5 million years. The indicated progressive deterioration of environmental and climatic conditions in the Siberian Arctic starting at ca. 3.3 Ma is consistent with the first occurrence of glacial periods and the finally complete establishment of glacial-interglacial cycles during the Quaternary.

(Table 3) Interannual variability of total mass flux at the deep sediment trap site CBmeso between 1988 and 2006

This article will review major features of the 'giant' Cape Blanc filament off Mauritania with regard to the transport of chlorophyll and organic carbon from the shelf to the open ocean. Within the filament, chlorophyll is transported about 400 km offshore. Modelled particle distributions along a zonal transect at 21°N showed that particles with a sinking velocity of 5 m d**-1 are advected offshore by up to 600 km in subsurface particle clouds generally located between 400 m and 800 m water depth, forming an Intermediate Nepheloid Layer (INL). It corresponds to the depth of the oxygen minimum zone. Heavier particles with a sinking velocity of 30 m d**-1 are transported from the shelf within the Bottom Layer (BL) of more than 1000 m thickness, largely following the topography of the bottom slope. The particles advected within the BL contribute to the enhanced winter-spring mass fluxes collected at the open-ocean mesotrophic sediment trap site CB-13 (200 nm offshore), due to a long distance advection in deeper waters. The lateral contribution to the deep sediment trap in winter-spring is estimated to be 63% and 72% for organic carbon and total mass, respectively, whereas the lateral input for both components on an annual basis is estimated to be in the order of 15%. Biogenic opal increases almost fivefold from the upper to the lower mesotrophic CB-13 trap, also pointing to an additional source for biogenic silica from eutrophic coastal waters. Blooms obviously sink in smaller, probably mesoscale-sized patches with variable settling rates, depending on the type of aggregated particles and their ballast content. Generally, particle sinking rates are exceptionally high off NW Africa. Very high chlorophyll values and a large size of the Cape Blanc filament in 1998-1999 are also documented in enhanced total mass and organic carbon fluxes. An increasing trend in satellite chlorophyll concentrations and the size of the Cape Blanc filament between 1997 and 2008 as observed for other coastal upwelling areas is not documented.

Fatty acids composition of Chylomicron remnants like particles influences their uptake and induction of lipid accumulation in macrophages.

The influence of the fatty acid composition of chylomicron remnant-like particles (CRLPs) on their uptake and induction of lipid accumulation in macrophages was studied. CRLPs containing triacylglycerol enriched in saturated, monounsaturated, n−6 or n−3 polyunsaturated fatty acids derived from palm, olive, corn or fish oil, respectively, and macrophages derived from the human monocyte cell line THP-1 were used. Lipid accumulation (triacylglycerol and cholesterol) in the cells was measured after incubation with CRLPs for 5, 24 and 48 h, and uptake over 24 h was determined using CRLPs radiolabelled with [3H]triolein. Total lipid accumulation in the macrophages was significantly greater with palm CRLPs than with the other three types of particle. This was mainly due to increased triacylglycerol concentrations, whereas changes in cholesterol concentrations did not reach significance. There were no significant differences in lipid accumulation after incubation with olive, corn or fish CRLPs. Palm and olive CRLPs were taken up by the cells at a similar rate, which was considerably faster than that observed with corn and fish CRLPs. These findings demonstrate that CRLPs enriched in saturated or monounsaturated fatty acids are taken up more rapidly by macrophages than those enriched in n−6 or n−3 polunsaturated fatty acids, and that the faster uptake rate results in greater lipid accumulation in the case of saturated fatty acid-rich particles, but not monounsaturated fatty acid-rich particles. Thus, dietary saturated fatty acids carried in chylomicron remnants may enhance their propensity to induce macrophage foam cell formation.