Appalachian Research Day: Come Sit on the Porch [2016]

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing innovative solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the community

Appalachian Research Day: Come Sit on the Porch

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing innovative solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the communit

Receptor use by pathogenic arenaviruses

The arenavirus family contains several important human pathogens including Lassa fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World clade B viruses Junin (JUNV) and Machupo (MACV). Previously, α-dystroglycan (α-DG) was identified as a receptor recognized by LASV and certain strains of LCMV. However, other studies have suggested that α-DG is probably not used by the clade B viruses, and the receptor(s) for these pathogens is currently unknown. Using pseudotyped retroviral vectors displaying arenavirus glycoproteins (GPs), we are able to explore the role played by the GP in viral entry in the absence of other viral proteins. By examining the ability of the vectors to transduce DG knockout murine embryonic stem (ES) cells, we have confirmed that LASV has an absolute requirement for α-DG in these cells. However, the LCMV GP can still direct substantial entry into murine ES cells in the absence of α-DG, even when the GP from the clone 13 variant is used that has previously been reported to be highly dependent on α-DG for entry. We also found that neither LASV or LCMV pseudotyped vectors were able to transduce human or murine lymphocytes, presumably due to the glycosylation state of α-DG in these cells. In contrast, the JUNV and MACV GPs displayed broad tropism on human, murine and avian cell types, including lymphocytes, and showed no requirement for α-DG in murine ES cells. These findings highlight the importance of molecules other than α-DG for arenavirus entry. An alternate receptor is present on murine ES cells that can be used by LCMV but not by LASV, and which is not available on human or murine lymphocytes, while a distinct and widely expressed receptor(s) is used by the clade B viruses.Facultad de Ciencias Exacta

Pasos Hacia La Salud: a randomized controlled trial of an internet-delivered physical activity intervention for Latinas.

BackgroundInternet access has grown markedly in Latinos during the past decade. However, there have been no Internet-based physical activity interventions designed for Latinos, despite large disparities in lifestyle-related conditions, such as obesity and diabetes, particularly in Latina women. The current study tested the efficacy of a 6-month culturally adapted, individually tailored, Spanish-language Internet-based physical activity intervention.MethodsInactive Latinas (N = 205) were randomly assigned to the Tailored Physical Activity Internet Intervention or the Wellness Contact Control Internet Group. Participants in both groups received emails on a tapered schedule over 6 months to alert them to new content on the website. The primary outcome was minutes/week of moderate to vigorous physical activity (MVPA) at 6 months as measured by the 7-Day Physical Activity Recall; activity was also measured by accelerometers. Data were collected between 2011 and 2014 and analyzed in 2015 at the University of California, San Diego.ResultsIncreases in minutes/week of MVPA were significantly greater in the Intervention Group compared to the Control Group (mean difference = 50.00, SE = 9.5, p < 0.01). Increases in objectively measured MVPA were also significantly larger in the Intervention Group (mean differences = 31.0, SE = 10.7, p < .01). The Intervention Group was also significantly more likely to meet national physical activity guidelines at 6 months (OR = 3.12, 95% CI 1.46-6.66, p < .05).ConclusionFindings from the current study suggest that this Internet-delivered individually tailored intervention successfully increased MVPA in Latinas compared to a Wellness Contact Control Internet Group.Trial registrationNCT01834287

Receptor use by pathogenic arenaviruses

The arenavirus family contains several important human pathogens including Lassa fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World clade B viruses Junin (JUNV) and Machupo (MACV). Previously, α-dystroglycan (α-DG) was identified as a receptor recognized by LASV and certain strains of LCMV. However, other studies have suggested that α-DG is probably not used by the clade B viruses, and the receptor(s) for these pathogens is currently unknown. Using pseudotyped retroviral vectors displaying arenavirus glycoproteins (GPs), we are able to explore the role played by the GP in viral entry in the absence of other viral proteins. By examining the ability of the vectors to transduce DG knockout murine embryonic stem (ES) cells, we have confirmed that LASV has an absolute requirement for α-DG in these cells. However, the LCMV GP can still direct substantial entry into murine ES cells in the absence of α-DG, even when the GP from the clone 13 variant is used that has previously been reported to be highly dependent on α-DG for entry. We also found that neither LASV or LCMV pseudotyped vectors were able to transduce human or murine lymphocytes, presumably due to the glycosylation state of α-DG in these cells. In contrast, the JUNV and MACV GPs displayed broad tropism on human, murine and avian cell types, including lymphocytes, and showed no requirement for α-DG in murine ES cells. These findings highlight the importance of molecules other than α-DG for arenavirus entry. An alternate receptor is present on murine ES cells that can be used by LCMV but not by LASV, and which is not available on human or murine lymphocytes, while a distinct and widely expressed receptor(s) is used by the clade B viruses.Facultad de Ciencias Exacta

Notes on Notebooks: Is Jupyter the Bringer of Jollity?

As the interactive computational notebook becomes a more prominent code development medium, we examine advantages and disadvantages of this particular source code format. We specify the structure of a coding notebook layout. We describe complexities in notebook programming; some of these are incidental whereas others may be inherent complexities. We outline how we envisage research and development might proceed to advance the cause of notebook programming

‘Knowledge exchange’ workshops to optimise development of a risk prediction tool to assist conveyance decisions for suspected seizures – Part of the Risk of ADverse Outcomes after a Suspected Seizure (RADOSS) project

Purpose Suspected seizures present challenges for ambulance services, with paramedics reporting uncertainty over whether or not to convey individuals to emergency departments. The Risk of ADverse Outcomes after a Suspected Seizure (RADOSS) project aims to address this by developing a risk assessment tool utilizing structured patient care record and dispatch data. It proposes a tool that would provide estimates of an individual's likelihood of death and/or recontact with emergency care within 3 days if conveyed compared to not conveyed, and the likelihood of an 'avoidable attendance' occurring if conveyed. Knowledge Exchange workshops engaged stakeholders to resolve key design uncertainties before model derivation. Method Six workshops involved 26 service users and their significant others (epilepsy or nonepileptic attack disorder), and 25 urgent and emergency care clinicians from different English ambulance regions. Utilizing Nominal Group Techniques, participants shared views of the proposed tool, benefits and concerns, suggested predictors, critiqued outcome measures, and expressed functionality preferences. Data were analysed using Hamilton’s Rapid Analysis. Results Stakeholders supported tool development, proposing 10 structured variables for predictive testing. Emphasis was placed on the tool supporting, not dictating, care decisions. Participants highlighted some reasons why RADOSS might struggle to derive a predictive model based on structured data alone and suggested some non-structured variables for future testing. Feedback on prediction timeframes for service recontact was received, along with advice on amending the 'avoidable attendance' definition to prevent the tool’s predictions being undermined by potential overuse of certain investigations in hospital. Conclusion Collaborative stakeholder engagement provided crucial insights that can guide RADOSS to develop a user-aligned, optimized tool

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts