Information Literacy and Student Engagement: Cultivating Student Learning through Critical Pedagogy and Critical Reflection

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HIV and Hepatitis C-Coinfected Patients Have Lower Low-Density Lipoprotein Cholesterol Despite Higher Proprotein Convertase Subtilisin Kexin 9 (PCSK9): An Apparent "PCSK9-Lipid Paradox".

BackgroundProprotein convertase subtilisin kexin 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) and improve outcomes in the general population. HIV-infected individuals are at increased risk for cardiovascular events and have high rates of dyslipidemia and hepatitis C virus (HCV) coinfection, making PCSK9 inhibition a potentially attractive therapy.Methods and resultsWe studied 567 participants from a clinic-based cohort to compare PCSK9 levels in patients with HIV/HCV coinfection (n=110) with those with HIV infection alone (n=385) and with uninfected controls (n=72). The mean age was 49 years, and the median LDL-C level was 100 mg/dL (IQR 77-124 mg/dL); 21% were taking statins. The 3 groups had similar rates of traditional risk factors. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol levels were lower in coinfected patients compared with controls (P<0.001). PCSK9 was 21% higher in HIV/HCV-coinfected patients versus controls (95% CI 9-34%, P<0.001) and 11% higher in coinfected individuals versus those with HIV infection alone (95% CI 3-20%, P=0.008). After adjustment for cardiovascular risk factors, HIV/HCV coinfection remained significantly associated with 20% higher PCSK9 levels versus controls (95% CI 8-33%, P=0.001). Interleukin-6 levels increased in a stepwise fashion from controls (lowest) to HIV-infected to HIV/HCV-coinfected individuals (highest) and correlated with PCSK9 (r=0.11, P=0.018).ConclusionsDespite having lower LDL-C, circulating PCSK9 levels were increased in patients coinfected with HIV and HCV in parallel with elevations in the inflammatory, proatherogenic cytokine interleukin-6. Clinical trials should be conducted to determine the efficacy of targeted PCSK9 inhibition in the setting of HIV/HCV coinfection

Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis

Human-Centric Process-Aware Information Systems (HC-PAIS)

Process-Aware Information Systems (PAIS) support organizations in managing and automating their processes. A full automation of processes is in particular industries, such as service-oriented markets, not practicable. The integration of humans in PAIS is necessary to manage and perform processes that require human capabilities, judgments and decisions. A challenge of interdisciplinary PAIS research is to provide concepts and solutions that support human integration in PAIS and human orientation of PAIS in a way that provably increase the PAIS users' satisfaction and motivation with working with the Human-Centric Process Aware Information System (HC-PAIS) and consequently influence users' performance of tasks. This work is an initial step of research that aims at providing a definition of Human-Centric Process Aware Information Systems (HC-PAIS) and future research challenges of HC-PAIS. Results of focus group research are presented.Comment: 8 page

Lignin-Modified Phenolic Syntan: A Contributor to Our Bio-Based Solutions

Content: In order to contribute to a more sustainable leather manufacturing process and leather value chain, in 2016 Smit & zoon started its own designing process of new products through the Bio-Based innovation platform. As a logical first step, answers to several key questions have been looked for: What is Bio-Based? What is renewable? Which term and method do we use to define the Bio-Based content in the Bio-Based platform? What is biodegradable? How do our current products perform? What is our vision for future products? In the process of answering these questions and guided by the Cradle-to-Cradle (C2C) CertifiedTM program, Material Reutilization Score (MRS) was used to obtain deeper insights into the formulation and environmental performance of our leather chemicals and treated as the basis for the design of new generation bio-based chemicals. Three main focus areas are setting the tone of current activities in the Bio-based platform: 1. increasing the renewable contents of the existing product groups; 2. smart valorization of industrial side streams from biological origin and 3. improving the biodegradability of leather chemicals. While focusing on these topics, it is well-understood that a proper balance needs to be found between cost, sustainability and performance. In the meantime, leather’s end of life scenario plays a role and needs to be looked at again. One of the first results of this focused approach is our patentpending polyphenolic syntan product, in which industrial lignins are used during the chemical conversion process to replace part of the phenol (40-50 w/w%) used in the production of otherwise 100% petro-based polyphenolic retanning chemicals. We have shown that our innovative technology is compatible with most of the industrial lignins (kraft, soda, organosolv, hydrolysis) from different origins (soft/hard wood, grass, straw). The obtained polyphenolic products have real tanning power and are suitable to be used as retanning agents for various types of leather rendering good organoleptic properties with additional added value of increased bio-based content, improved biodegradability thus a higher MRS. The improved biodegradability of these products can contribute to decrease the effluent treatment load. Moreover, these products can be tailor-made to meet low emission (low free phenol, low free formaldehyde) requirements as well. In addition to the lignin-based polymers, the quickly developing project portfolio within the biobased platform manifests that Smit & zoon is making steady steps towards a largely sustainable leather value chain by 2025. Take-Away: Bio-Based products contritbute to a sustainable leather manufacturing process and leather value chain. Both the raw material renewability and product biodegradability are important parameters to evaluate the environmental impact of leather chemicals. Smit & zoon has developed a patent-pending bio-based synthan product using industrial lignins to replace part of the petro-based phenols in the production process

Phenology and interspecific association of Forficula auricularia and Forficula pubescens in apple orchards

The European earwig Forficula auricularia L. (Dermaptera: Forficulidae) has been widely studied as a key predator of pests in temperate regions, but its phenology and behavior may differ in warmer areas such as the Mediterranean. Here we assessed the phenology, aggregation, and interspecific association of F. auricularia and Forficula pubescens Gené, the only two species found consistently in both ground and canopy shelters in Mediterranean apple orchards. In addition to F. auricularia and F. pubescens, three other earwig species, namely Labidura riparia Pallas, Nala lividipes Dufour and Euborellia moesta Gené, were found occasionally. The mature stages of F. auricularia were observed mainly from May to November in tree shelters and immature ones from October to June in ground shelters. Adult individuals of F. pubescens were observed year-round and nymph instars were detected from April to June in ground as well as in tree shelters. The suitability of the current degree-days models for temperate regions was evaluated for the prediction of European earwig phenology in a Mediterranean climate. Regarding interspecific association, F. auricularia and F. pubescens co-occurred in canopies without apparent competition. This study provides useful weekly data about the phenology of the two earwig species throughout the year that can be used to detect the key periods during which to enhance their populations in pip fruit orchards or to control them in stone fruit crops. Furthermore, our results are of relevance for the development of new phenological models of earwigs in Mediterranean areas where nymphs hibernate, a feature that makes current models inaccurate.Funding: This study was funded by the Spanish project Programa Nacional de Investigación y Desarrollo Agrario nº AGL2010- 17486 (AGR) Control integrado de plagas en frutales de pepita y hueso

Close Encounters of Tight Binary Stars with Stellar-mass Black Holes

Strong dynamical interactions among stars and compact objects are expected in a variety of astrophysical settings, such as star clusters and the disks of active galactic nuclei. Here, via a suite of 3D hydrodynamics simulations using the moving-mesh code {\small AREPO}, we investigate the effect of close encounters between an equal-mass circular binary star with mass of $2M_{\odot}$ or $20M_{\odot}$ and single $20M_{\odot}$ black hole (BH), focusing on the formation of transient phenomena and their properties. Stars can be disrupted by the BH during three-body dynamical interactions, naturally producing electromagnetic transient phenomena. Encounters with impact parameters smaller than the semimajor axis of the initial binary frequently lead to a variety of transients whose electromagnetic signatures are qualitatively different from those of ordinary tidal disruption events involving just two bodies. These include the simultaneous or successive full disruptions of both stars and one full disruption of one star accompanied by successive partial disruptions of the other star. On the other hand, when the impact parameter is larger than the semimajor axis of the initial binary, the binary is either simply tidally perturbed or dissociated into bound and unbound single stars (``micro-Hills'' mechanism). We found that the dissociation of binaries consisting of $10M_{\odot}$ stars can produce the formation of a runaway star and an active isolated BH moving away from one another. Also, one of the unbound stars produced in the binary dissociation can either form an interacting binary with the BH, or a non-interacting, hard binary (which may later shrink via weak encounters); both of these could be candidates of BH high- and low-mass X-ray binaries with periodic luminosity modulation.Comment: 13 pages, 8 figures, 2 tables. submitted to MNRAS. Comments welcome