The Legacy Project: Lessons Learned About Conducting Community-Based Research

Collaborative partnerships between community based organizations (CBOs) and university-based researchers can successfully conduct useful HIV prevention research. Collaboratively conducted research contributes to good programs and good science.The Legacy Project is an evaluation of 18 such partnerships. The evaluation found 6 essential elements for successful collaborative community-based research:Thoughtful selection of interventions for evaluationSecondary or alternative research questions incorporated into the research project from the beginningFlexibility to modify or change primary research question mid-studyAppropriate, stable CBO staffingHigh level of university-researcher involvement with both intervention and evaluationAdequate funding for intervention, evaluation and participant tim

A Writer, an Editor, an Instructor, and an Alumna Walk into the Writing Center

As the writing center director, I believe our professional tutors provide valuable expert perspectives to student writers. They also help me mentor the peer tutors and push me to reevaluate our practices. They add staffing stability to the center (whose peer tutors never stay for more than three years). Finally, these trusted writing experts professionalize the writing center’s status among administration, faculty, and students. In the following paragraphs, Amy, Ellen, Chris, and Lindsey illustrate the rich variety of skills and perspectives professional writing tutors can contribute to a writing centerUniversity Writing Cente

Constitutional Analogies in the International Legal System

This Article explores issues at the frontier of international law and constitutional law. It considers five key structural and systemic challenges that the international legal system now faces: (1) decentralization and disaggregation; (2) normative and institutional hierarchies; (3) compliance and enforcement; (4) exit and escape; and (5) democracy and legitimacy. Each of these issues raises questions of governance, institutional design, and allocation of authority paralleling the questions that domestic legal systems have answered in constitutional terms. For each of these issues, I survey the international legal landscape and consider the salience of potential analogies to domestic constitutions, drawing upon and extending the writings of international legal scholars and international relations theorists. I also offer some preliminary thoughts about why some treaties and institutions, but not others, more readily lend themselves to analysis in constitutional terms. And I distinguish those legal and political issues that may generate useful insights for scholars studying the growing intersections of international and constitutional law from other areas that may be more resistant to constitutional analogies

Responsibility for HIV Prevention: Patterns of Attribution Among HIV-seropositive Gay and Bisexual Men

The article presents research based on narratives by gay and bisexual men recently infected with HIV. Researchers looked at the men\u27s attributions of responsibility for infection, comparing recollections of feelings before becoming infected with views expressed after seroconversion. The research responds to a call to better understand risk behavior among HIV-positive persons, in an effort to craft effective prevention interventions. In both before-and after-HIV infection views, survey participants expressed a sense of personal responsibility. Researchers report also nuances of views about shared responsibility

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

AbstractHirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene–gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children

Beyond nudges: Tools of a choice architecture

The way a choice is presented influences what a decision-maker chooses. This paper outlines the tools available to choice architects, that is anyone who present people with choices. We divide these tools into two categories: those used in structuring the choice task and those used in describing the choice options. Tools for structuring the choice task address the idea of what to present to decision-makers, and tools for describing the choice options address the idea of how to present it. We discuss implementation issues in using choice architecture tools, including individual differences and errors in evaluation of choice outcomes. Finally, this paper presents a few applications that illustrate the positive effect choice architecture can have on real- world decisions

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

A Nd Isotopic Study of Southern Sourced Waters and Indonesian Throughflow at Intermediate Depths in the Cenozoic Indian Ocean

We present Nd isotopic data for fossil fish teeth recovered from the past 40 m.y. at ODP Site 757, currentlylocated at 1650m water depth on the Ninetyeast Ridge in the Indian Ocean. Although Site 757 sits in a regionstrongly influenced by weathering inputs from the Himalayas and volcanic inputs from the Indonesian arc, the pattern of Nd isotopic variations does not appear to respond to these potential sources of Nd. Instead, secular variations correlate to changes in the composition of intermediate to deep water masses bathing thesite and circulation patterns in the Indian Ocean. From ~40 to 10 Ma, eNd values and the pattern of change at Site 757 closely match those of ODP Site 1090, a deep water site in the Atlantic sector of the Southern Ocean. Comparison to data from several Fe-Mn crusts in the Indian Ocean suggests that intermediate to deep waterflow paths were similar to the modern distribution of Circumpolar DeepWater. At approximately 10 Ma, Ndisotopic values increase in a step function by 2 eNd units, suggesting that plate motions had carried Site 757into a region influenced by Indonesian Throughflow. Estimates of the vertical and horizontal position of thissite at 10 Ma imply that Indonesian Throughflow extended as far south as ~20S and to a depth of ~1500 m. From 10 to 0 Ma, Nd isotopic variations at Site 757 appear to record variations in Indonesian Throughflow. From 10 to 5.5 Ma, values at Site 757 overlap with those from crusts located in the southwest Pacific,indicating extensive flow through the Indonesian Seaway. From 5.5 to 3.4 Ma, eNd values become lessradiogenic at Site 757 and more radiogenic in the southwest Pacific, suggesting increasing closure of theseaway and concomitant rerouting of equatorial Pacific waters. Beginning at 3.4 Ma, eNd values becomemore radiogenic again at Site 757, which may be attributed to enhanced opening of the seaway or to a changein the source of Throughflow waters from a southern to a northern Pacific region