Shipping Receipt GM Partridge Dec 10 1862

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Shipping Receipt GM Partridge December 22 1858

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Resistance to the CCR5 Inhibitor 5P12-RANTES Requires a Difficult Evolution from CCR5 to CXCR4 Coreceptor Use

Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC) or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16–18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a “resistant” variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching

An assessment of technology-based service encounters & network security on the e-health care systems of medical centers in Taiwan

<p>Abstract</p> <p>Background</p> <p>Enhancing service efficiency and quality has always been one of the most important factors to heighten competitiveness in the health care service industry. Thus, how to utilize information technology to reduce work load for staff and expeditiously improve work efficiency and healthcare service quality is presently the top priority for every healthcare institution. In this fast changing modern society, e-health care systems are currently the best possible way to achieve enhanced service efficiency and quality under the restraint of healthcare cost control. The electronic medical record system and the online appointment system are the core features in employing e-health care systems in the technology-based service encounters.</p> <p>Methods</p> <p>This study implemented the Service Encounters Evaluation Model, the European Customer Satisfaction Index, the Attribute Model and the Overall Affect Model for model inference. A total of 700 copies of questionnaires from two authoritative southern Taiwan medical centers providing the electronic medical record system and the online appointment system service were distributed, among which 590 valid copies were retrieved with a response rate of 84.3%. We then used SPSS 11.0 and the Linear Structural Relationship Model (LISREL 8.54) to analyze and evaluate the data.</p> <p>Results</p> <p>The findings are as follows: (1) Technology-based service encounters have a positive impact on service quality, but not patient satisfaction; (2) After experiencing technology-based service encounters, the cognition of the service quality has a positive effect on patient satisfaction; and (3) Network security contributes a positive moderating effect on service quality and patient satisfaction.</p> <p>Conclusion</p> <p>It revealed that the impact of electronic workflow (online appointment system service) on service quality was greater than electronic facilities (electronic medical record systems) in technology-based service encounters. Convenience and credibility are the most important factors of service quality in technology-based service encounters that patients demand. Due to the openness of networks, patients worry that transaction information could be intercepted; also, the credibility of the hospital involved is even a bigger concern, as patients have a strong sense of distrust. Therefore, in the operation of technology-based service encounters, along with providing network security, it is essential to build an atmosphere of psychological trust.</p

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports

Does Television Exposure Affect Emerging Adults' Attitudes and Assumptions About Sexual Relationships? Correlational and Experimental Confirmation

Because concern is frequently raised that TV's abundant yet stereotypical portrayals of sexual relationships may mislead young viewers, this study examined the effects of both regular viewing habits and experimental exposure on students' conceptions about sexual relationships. A multiethnic sample of 259 undergraduates aged 18–22 was assigned to view a set of clips depicting either 1 of 3 sexual stereotypes or neutral, nonsexual content. Participants then completed measures assessing their attitudes about sexual roles and relationships, their assumptions about the sexual experiences of their peers, and their regular viewing habits. Both correlational and experimental connections emerged between TV viewing and students' sexual attitudes and assumptions. More frequent and more involved viewing were repeatedly associated with students' support of the sexual stereotypes surveyed. Similarly, women exposed to clips representing a particular sexual stereotype were more likely to endorse that notion than were women exposed to nonsexual content. Finally, both experimental exposure and aspects of regular viewing significantly predicted students' sexual attitudes and assumptions, even with demographics and previous sexual experiences controlled.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45292/1/10964_2004_Article_364602.pd

Shipping Receipt GM Partridge December 22 1858

https://digitalmaine.com/blue_hill_documents/1140/thumbnail.jp

Shipping Receipt GM Partridge Dec 10 1862

https://digitalmaine.com/blue_hill_documents/1139/thumbnail.jp

Exploratory Evaluation of Bezlotoxumab on Outcomes Associated With Clostridioides difficile Infection in MODIFY I/II Participants With Cancer

Background. The incidence of Clostridioides dtfficile infection (CDI) is reportedly higher and the cure rate lower in individuals with cancer vs those without cancer. An exploratory post hoc analysis of the MODIFY I/II trials (NCT01241552/NCT01513239) investigated how bezlotoxumab affected the rate of CDI-related outcomes in participants with cancer. Methods. Participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI antibacterial treatment. A post hoc analysis of CDI-related outcomes was conducted in subgroups of MODIFY I/II participants with and without cancer. Results. Of 1554 participants in the modified intent-to-treat (mITT) population, 382 (24.6%) were diagnosed with cancer (bezlotoxumab 190, placebo 192). Of participants without cancer, 591 and 581 received bezlotoxumab and placebo, respectively. In the placebo group, initial clinical cure (ICC) was achieved by fewer cancer participants vs participants without cancer (71.9% vs 83.1%; absolute difference, -11.3%; 95% CI, -18.6% to -4.5%); however, CDI recurrence (rCDI) rates were similar in cancer (30.4%) and noncancer (34.0%) participants. In participants with cancer, bezlotoxumab treatment had no effect on ICC rate compared with placebo (76.8% vs 71.9%), but resulted in a statistically significant reduction in rCDI vs placebo (17.8% vs 30.4%; absolute difference, -12.6%; 95% CI, -22.5% to -2.7%). Conclusions. In this post hoc analysis of participants with cancer enrolled in MODIFY I/II, the rate of rCDI in bezlotoxumabtreated participants was lower than in placebo-treated participants. Additional studies are needed to confirm these results