Chromatographic determination of hydrocarbons based on retention time data for squalene and tetracyanoethylated pentaerythritol columns

The purpose of this thesis is to investigate the theory that when several members of a homologous series are injected into a gas chromatograph, at a given flow rate and column temperature, the lograrithm of their retention time as a function of some increasing property of the homologous series may be presented as a straight line and to develop their equations. Experimental procedure was accomplished for the normal paraffin series with 7 1/2% squalene and 10% Tetracyanoethylated Pentaerythritol (T.C.E.pageE.) columns and the relation between retention time and carbon number was determined. The same type of development was employed for aromatic compounds with a 10% T.C.E.pageE. column and the relation between retention time and boiling point of the compound was ascertained --Abstract, page ii

A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk

Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated

Quality in Tourism Literature: A Bibliometric Review

[EN] The literature about quality has experienced an important expansion in the tourism sector in the last decade. This is a result of the importance of quality issues when attempting to maintain and expand sustainable business models for tourism organizations and destinations, which are critical to strengthen competitiveness in the new framework. This relevance has been reflected in the tourism literature, with numerous papers focusing on the topic of quality. Nevertheless, despite its importance, there is a lack of studies and reviews of this literature. In order to overcome this problem, this paper develops a bibliometric and visualization analysis of the literature that examines the topics of tourism and quality together. Specifically, the article studies the 4625 documents on this issue published until the end of 2018 in the Web of Science Core Collection database, by using the co-occurrence of keywords, co-citation, bibliographic coupling, and co-authorship analyses. In addition, the VOSviewer program was used to map the diverse clusters or relationships among the literature. The results showed the trends and impact of this literature, and also the main papers, authors, journals, institutions, and even countries that focus on tourism and quality aspects together. They are useful for researchers and practitioners when dealing with this topic, in order to better understand the situation of this issue and its development.This research was funded by Universitat Politecnica de Valencia, Universitat Jaume I. and The APC was funded by Walailak University.Garrigós Simón, FJ.; Narangajavana-Kaosiri, Y.; Narangajavana, Y. (2019). Quality in Tourism Literature: A Bibliometric Review. Sustainability. 11(14):1-22. https://doi.org/10.3390/su11143859S1221114Armenski, T., Dwyer, L., & Pavluković, V. (2017). Destination Competitiveness: Public and Private Sector Tourism Management in Serbia. 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Journal of Travel & Tourism Marketing, 26(8), 836-853. doi:10.1080/10548400903358729Zeithaml, V. A., Berry, L. L., & Parasuraman, A. (1996). The Behavioral Consequences of Service Quality. Journal of Marketing, 60(2), 31. doi:10.2307/1251929Lynn Shostack, G. (1982). How to Design a Service. European Journal of Marketing, 16(1), 49-63. doi:10.1108/eum0000000004799Crompton, J. L., & Love, L. L. (1995). The Predictive Validity of Alternative Approaches to Evaluating Quality of a Festival. Journal of Travel Research, 34(1), 11-24. doi:10.1177/004728759503400102Wu, H.-C., Li, M.-Y., & Li, T. (2014). A Study of Experiential Quality, Experiential Value, Experiential Satisfaction, Theme Park Image, and Revisit Intention. Journal of Hospitality & Tourism Research, 42(1), 26-73. doi:10.1177/1096348014563396Atilgan, E., Akinci, S., & Aksoy, S. (2003). Mapping service quality in the tourism industry. 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R. (2015). An overview of fuzzy research with bibliometric indicators. Applied Soft Computing, 27, 420-433. doi:10.1016/j.asoc.2014.10.035Hirsch, J. E. (2005). An index to quantify an individual’s scientific research output. Proceedings of the National Academy of Sciences, 102(46), 16569-16572. doi:10.1073/pnas.0507655102Van Eck, N. J., & Waltman, L. (2009). Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics, 84(2), 523-538. doi:10.1007/s11192-009-0146-3Small, H. (1973). Co-citation in the scientific literature: A new measure of the relationship between two documents. Journal of the American Society for Information Science, 24(4), 265-269. doi:10.1002/asi.4630240406Kessler, M. M. (1963). Bibliographic coupling between scientific papers. American Documentation, 14(1), 10-25. doi:10.1002/asi.5090140103Liao, H., Tang, M., Luo, L., Li, C., Chiclana, F., & Zeng, X.-J. (2018). A Bibliometric Analysis and Visualization of Medical Big Data Research. Sustainability, 10(2), 166. doi:10.3390/su10010166Chen, C.-F., & Chen, F.-S. (2010). Experience quality, perceived value, satisfaction and behavioral intentions for heritage tourists. Tourism Management, 31(1), 29-35. doi:10.1016/j.tourman.2009.02.008Fornell, C., & Larcker, D. F. (1981). Evaluating Structural Equation Models with Unobservable Variables and Measurement Error. Journal of Marketing Research, 18(1), 39-50. doi:10.1177/002224378101800104Yoon, Y., & Uysal, M. (2005). An examination of the effects of motivation and satisfaction on destination loyalty: a structural model. Tourism Management, 26(1), 45-56. doi:10.1016/j.tourman.2003.08.016Zeithaml, V. A. (1988). Consumer Perceptions of Price, Quality, and Value: A Means-End Model and Synthesis of Evidence. Journal of Marketing, 52(3), 2-22. doi:10.1177/002224298805200302Cronin, J. J., Brady, M. K., & Hult, G. T. M. (2000). 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Cognitive function in a randomized trial of evolocumab

Inga Stuķēna as well as a complete list of investigators is provided in the Supplementary Appendix, available at NEJM.org. https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701131/suppl_file/nejmoa1701131_appendix.pdf Funding Information: (Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634.) Supported by Amgen. We thank Sarah T. Farias, Ph.D., at UC Davis Health for providing the English-language and translated versions of the Everyday Cognition (ECog) tool. Publisher Copyright: Copyright © 2017 Massachusetts Medical Society.BACKGROUND: Findings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. METHODS: In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. RESULTS: A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was −0.21±2.62 in the evolocumab group and −0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, −0.52 in the evolocumab group and −0.93 in the placebo group), episodic memory (change in raw score, −1.53 and −1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes. CONCLUSIONS: In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months.publishersversionPeer reviewe

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain.We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years.At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%).In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633 .)

Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure

Imaging of caspase activation in living mouse embryos during development suggests that caspase-mediated cell removal facilitates neural tube closure in a temporally regulated manner

Multiple Apoptotic Caspase Cascades Are Required in Nonapoptotic Roles for Drosophila Spermatid Individualization

Spermatozoa are generated and mature within a germline syncytium. Differentiation of haploid syncytial spermatids into single motile sperm requires the encapsulation of each spermatid by an independent plasma membrane and the elimination of most sperm cytoplasm, a process known as individualization. Apoptosis is mediated by caspase family proteases. Many apoptotic cell deaths in Drosophila utilize the REAPER/HID/GRIM family proapoptotic proteins. These proteins promote cell death, at least in part, by disrupting interactions between the caspase inhibitor DIAP1 and the apical caspase DRONC, which is continually activated in many viable cells through interactions with ARK, the Drosophila homolog of the mammalian death-activating adaptor APAF-1. This leads to unrestrained activity of DRONC and other DIAP1-inhibitable caspases activated by DRONC. Here we demonstrate that ARK- and HID-dependent activation of DRONC occurs at sites of spermatid individualization and that all three proteins are required for this process. dFADD, the Drosophila homolog of mammalian FADD, an adaptor that mediates recruitment of apical caspases to ligand-bound death receptors, and its target caspase DREDD are also required. A third apoptotic caspase, DRICE, is activated throughout the length of individualizing spermatids in a process that requires the product of the driceless locus, which also participates in individualization. Our results demonstrate that multiple caspases and caspase regulators, likely acting at distinct points in time and space, are required for spermatid individualization, a nonapoptotic process

F-box Protein FBXL16 Binds PP2A-B55α and Regulates Differentiation of Embryonic Stem Cells along the FLK1+ Lineage

The programmed formation of specific tissues from embryonic stem cells is a major goal of regenerative medicine. To identify points of intervention in cardiac tissue formation, we performed an siRNA screen in murine embryonic stem cells to identify ubiquitin system genes that repress cardiovascular tissue formation. Our screen uncovered an F-box protein, Fbxl16, as a repressor of one of the earliest steps in the cardiogenic lineage: FLK1+ progenitor formation. Whereas F-box proteins typically form SCF ubiquitin ligases, shotgun mass spectrometry revealed that FBXL16 instead binds protein phosphatase 2A (PP2A) containing a B55 specificity subunit (PP2A^(B55)). Phosphoproteomic analyses indicate that FBXL16 negatively regulates phosphorylation of the established PP2AB55 substrate, vimentin. We suggest that FBXL16 negatively regulates the activity of B55α-PP2A to modulate the genesis of FLK1+ progenitor cells

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death