A series of bis[[(carbamoyl)oxy]methyl]-substituted pyrrole-fused tricyclic heterocycles were synthesized by using 1,3-dipolar cycloaddition reactions with a trifluoromethanesulfonate salt of an appropriate Resissert compound or with a mesoionic oxazolone intermediate. All of the bis(carbamates) were active in vivo against P388 lymphocytic leukemia with 5,6-dihydro-8-methoxy-1,2- bis(hydroxymethyl)pyrrolo[2,1-a]isoquinoline bis[N-(2-propyl)carbamate] (3c) showing the highest level of activity.

Use of diabetes registries meeting Meaningful Use core objectives is associated with higher completion or recommended lab tests and a lower hospital utilization rate for patients with type 2 diabetes.

This qualitative study identified challenges and unexpected benefits that might inform future efforts. Communication and integration between the TM agency and the practice, including the designation of a point person within the office to coordinate TM and help address the broader contextual needs of patients, are important considerations for future implementation. The role of the TM nurse in developing trust with patients and uncovering the social and economic context within which patients manage their diabetes was an unexpected benefit.

Purpose:Unprecedented efforts are underway across the United States to electronically capture and exchange health information to improve health care and population health, and reduce costs. This increased collection and sharing of electronic patient data raises several governance issues, including privacy, security, liability, and market competition. Those engaged in such efforts have had to develop data sharing agreements (DSAs) among entities involved in information exchange, many of whom are “nontraditional” health care entities and/or new partners. This paper shares lessons learned based on the experiences of six federally funded communities participating in the Beacon Community Cooperative Agreement Program, and offers guidance for navigating data governance issues and developing DSAs to facilitate community-wide health information exchange.Innovation:While all entities involved in electronic data sharing must address governance issues and create DSAs accordingly, until recently little formal guidance existed for doing so – particularly for community-based initiatives. Despite this lack of guidance, together the Beacon Communities’ experiences highlight promising strategies for navigating complex governance issues, which may be useful to other entities or communities initiating information exchange efforts to support delivery system transformation.Credibility:For the past three years, AcademyHealth has provided technical assistance to most of the 17 Beacon Communities, 6 of whom contributed to this collaborative writing effort. Though these communities varied widely in terms of their demographics, resources, and Beacon-driven priorities, common themes emerged as they described their approaches to data governance and DSA development.Conclusions:The 6 Beacon Communities confirmed that DSAs are necessary to satisfy legal and market-based concerns, and they identified several specific issues, many of which have been noted by others involved in network data sharing initiatives. More importantly, these communities identified several promising approaches to timely and effective DSA development, including: stakeholder engagement; identification and effective communication of value; adoption of a parsimonious approach; attention to market-based concerns; flexibility in adapting and expanding existing agreements and partnerships; and anticipation of required time and investment.

Introduction of a reactive 5-mercapto group into some of the cytosine and/or uracil bases of various oligoand polynucleotides by partial thiolation resulted in several potent inhibitors of the replication of human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. These compounds exhibited little if any toxicity against uninfected peripheral blood mononuclear cells and showed 15 to 75 times higher antitemplate activity against a p66/p5i HIV-1 recombinant reverse transcriptase (RT) than against the DNA polymerase a from human lymphocytes. In contrast, the unthiolated oligo-and polynucleotides are void of antitemplate activity, and their apparent inhibitory effect on HIV-1 closely paralleled their toxicity for the cells. Partially thiolated poly(dC) (MPdC) was the most potent of all the compounds tested against HIV-1 in peripheral blood mononuclear cells (50% effective concentration, 1.8 ,ug/ml or 0.019 ,uM), while showing low cytotoxicity (>100 ,ug/ml). The corresponding unmodified poly(dC) showed no anti-HIV-1 activity at 50 ,ug/ml but had pronounced cytotoxicity. MPdC was also a potent inhibitor of HIV-1 RT (50% inhibitory concentration, 0.30 ,ug/ml). The inhibitory activities of thiolated homooligo(dCs) against both HIV-1 replication and HIV-1 RT increased with increasing chain length. The heterooligonucleotides included in this study were designed as structural analogs of portions of the natural primer of HIV-1 RT, i.e., tRNArYs. An 18-mer analog of the 3' terminus, complementary (antisense) to the primer-binding site of the HIV-1 genome, was attached to an oligo(dC) tail and 5-thiolated; this increased its activity and decreased its toxicity. This compound will serve as a new lead in the development of more effective antitemplates against HIV-1.