Aligning Community-Engaged Research to Context.

Community-engaged research is understood as existing on a continuum from less to more community engagement, defined by participation and decision-making authority. It has been widely assumed that more is better than less engagement. However, we argue that what makes for good community engagement is not simply the extent but the fit or alignment between the intended approach and the various contexts shaping the research projects. This article draws on case studies from three Community Engagement Cores (CECs) of NIEHS-funded Environmental Health Science Core Centers (Harvard University, UC Davis and University of Arizona,) to illustrate the ways in which community engagement approaches have been fit to different contexts and the successes and challenges experienced in each case. We analyze the processes through which the CECs work with researchers and community leaders to develop place-based community engagement approaches and find that different strategies are called for to fit distinct contexts. We find that alignment of the scale and scope of the environmental health issue and related research project, the capacities and resources of the researchers and community leaders, and the influences of the sociopolitical environment are critical for understanding and designing effective and equitable engagement approaches. These cases demonstrate that the types and degrees of alignment in community-engaged research projects are dynamic and evolve over time. Based on this analysis, we recommend that CBPR scholars and practitioners select a range of project planning and management techniques for designing and implementing their collaborative research approaches and both expect and allow for the dynamic and changing nature of alignment

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

An evaluation of a multi-component adult weight management on referral intervention in a community setting

BACKGROUND: National Institute for Health and Care Excellence (NICE) guidance on adult weight management recommends interventions are multi-component. We aimed to assess the implementation and health benefits of a primary care referral to an adult multi-component weight management intervention in a community setting. The intervention was offered through Primary care in National Health Service (NHS) South Gloucestershire, UK, from Oct 2008 to Nov 2010, in partnership with statutory, community and commercial providers. The scheme offered 12 weeks’ community based concurrent support of dietary (Weight Watchers, WW), physical activity (Exercise on Prescription, EOP) and behavioural change (motivational interviewing) components to obese adults. Funding was available for 600 places. RESULTS: Five hundred and fifty nine participants engaged with the intervention, mean age 48 years, 88 % female. Mean weight loss for all engagers was 3.7 kg (95 % confidence interval 3.4, 4.1). Participants completing the intervention achieved the largest weight reduction (mean loss 5.9 kg; 5.3, 6.6). Achievement of 5 % weight loss was higher in completers (58 %; 50, 65) compared to non-completers (19 %; 12, 26) and people who only participated in one commercial component of the intervention (either WW or EOP; 19 %; 13, 24). CONCLUSION: A multi-component weight management programme may be beneficial for weight loss, but a randomized controlled trial is needed to establish effectiveness and to evaluate cost

Velocity Segregation and Systematic Biases In Velocity Dispersion Estimates With the SPT-GMOS Spectroscopic Survey

The velocity distribution of galaxies in clusters is not universal; rather, galaxies are segregated according to their spectral type and relative luminosity. We examine the velocity distributions of different populations of galaxies within 89 Sunyaev Zel'dovich (SZ) selected galaxy clusters spanning $0.28 < z < 1.08$. Our sample is primarily draw from the SPT-GMOS spectroscopic survey, supplemented by additional published spectroscopy, resulting in a final spectroscopic sample of 4148 galaxy spectra---2868 cluster members. The velocity dispersion of star-forming cluster galaxies is $17\pm4$% greater than that of passive cluster galaxies, and the velocity dispersion of bright ($m < m^{*}-0.5$) cluster galaxies is $11\pm4$% lower than the velocity dispersion of our total member population. We find good agreement with simulations regarding the shape of the relationship between the measured velocity dispersion and the fraction of passive vs. star-forming galaxies used to measure it, but we find a small offset between this relationship as measured in data and simulations in which suggests that our dispersions are systematically low by as much as 3\% relative to simulations. We argue that this offset could be interpreted as a measurement of the effective velocity bias that describes the ratio of our observed velocity dispersions and the intrinsic velocity dispersion of dark matter particles in a published simulation result. Measuring velocity bias in this way suggests that large spectroscopic surveys can improve dispersion-based mass-observable scaling relations for cosmology even in the face of velocity biases, by quantifying and ultimately calibrating them out.Comment: Accepted to ApJ; 21 pages, 11 figures, 5 table

Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells

Landscape of stimulation-responsive chromatin across diverse human immune cells.

A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells

The Grizzly, December 9, 2004

Wendell Berry Visits Ursinus • In Memory of Mrs.Margot Richter • UC Theater Production Goes on the Road • DSAC Updates • New Honor Code at UC? • Ursinus Students Bring the Holidays to Campus • Civil Rights Movement Class Opens Minds • History Behind the Holidays • Reading Day • SAAC Clothing Drive • Opinions: Should Procrastination be Diagnosed as a Psychological Disease?; Out with Final Exams! Students Prefer Writing Papers; Letter to the Editor • Stanton\u27s Jersey Officially Retiredhttps://digitalcommons.ursinus.edu/grizzlynews/1574/thumbnail.jp

The Grizzly, September 23, 2004

Get Down in the Lounge • USGA Amendments Cause Controversy • Wismer Rumors Exposed • Family Day is Just Around the Corner • You got SERVed! • Medulla: Soul for Your Brain • Lead the Way: UC Leadership Studies Program • Care to Dance? • Opinions: Should More Public Places Move Towards a Complete No-smoking Policy?; Tattoo or not to Tattoo? • My Summer Vacation Camping at Death Pond • The Kobe Bryant Sagahttps://digitalcommons.ursinus.edu/grizzlynews/1565/thumbnail.jp

The Grizzly, March 3, 2005

Students Connect at the Job and Internship Fair • Who\u27s Teaching Your Class Today? • Jet Heiko of Turn Your Back on Bush Visits UC • Davis Lecturer Stresses Oral Tradition • The Stories of Our Lives : Presentation by Reverend Doctor Claudia Highbaugh • Finding the Goddess Within: Exploration of the G-Spot • Straight from the Detention Center: Review of The Face in the Mirror • Opinions: Borgata Bans Belly Bulge; Laundry Isn\u27t That Hard!; Selfish Fun or Selfless Act? What to do on Spring Break • Bears Down F&M for a 72-70 Centennial Conference Victory • Men\u27s Lacrosse 2005 Previewhttps://digitalcommons.ursinus.edu/grizzlynews/1580/thumbnail.jp