Co-delivery of human cancer-testis antigens with adjuvant in protein nanoparticles induces higher cell-mediated immune responses.

Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-γ secretion in HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity toward target cancer cells expressing the antigen. Immunization with a MAGE-A3 epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in specific IFN-γ secretion and cell lysis by 6-fold and 9-fold, respectively. Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2 nanoparticles yielded an additive effect that increased lytic activity towards cells bearing NY-ESO-1+ and MAGE-A3+. Our investigations demonstrate that formulation of CT antigens within a nanoparticle can significantly enhance antigen-specific cell-mediated responses, and the combination of the two antigens in a vaccine can preserve the increased individual responses that are observed for each antigen alone

Two to Five Truths in Non-Negative Matrix Factorization

In this paper, we explore the role of matrix scaling on a matrix of counts when building a topic model using non-negative matrix factorization. We present a scaling inspired by the normalized Laplacian (NL) for graphs that can greatly improve the quality of a non-negative matrix factorization. The results parallel those in the spectral graph clustering work of \cite{Priebe:2019}, where the authors proved adjacency spectral embedding (ASE) spectral clustering was more likely to discover core-periphery partitions and Laplacian Spectral Embedding (LSE) was more likely to discover affinity partitions. In text analysis non-negative matrix factorization (NMF) is typically used on a matrix of co-occurrence ``contexts'' and ``terms" counts. The matrix scaling inspired by LSE gives significant improvement for text topic models in a variety of datasets. We illustrate the dramatic difference a matrix scalings in NMF can greatly improve the quality of a topic model on three datasets where human annotation is available. Using the adjusted Rand index (ARI), a measure cluster similarity we see an increase of 50\% for Twitter data and over 200\% for a newsgroup dataset versus using counts, which is the analogue of ASE. For clean data, such as those from the Document Understanding Conference, NL gives over 40\% improvement over ASE. We conclude with some analysis of this phenomenon and some connections of this scaling with other matrix scaling methods

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science : Seattle, WA, USA. 24-26 September 2015.

Introduction to the 3rd Biennial Conference of the Society for Implementation Research Collaboration: advancing efficient methodologies through team science and community partnerships Cara Lewis, Doyanne Darnell, Suzanne Kerns, Maria Monroe-DeVita, Sara J. Landes, Aaron R. Lyon, Cameo Stanick, Shannon Dorsey, Jill Locke, Brigid Marriott, Ajeng Puspitasari, Caitlin Dorsey, Karin Hendricks, Andria Pierson, Phil Fizur, Katherine A. Comtois A1: A behavioral economic perspective on adoption, implementation, and sustainment of evidence-based interventions Lawrence A. Palinkas A2: Towards making scale up of evidence-based practices in child welfare systems more efficient and affordable Patricia Chamberlain A3: Mixed method examination of strategic leadership for evidence-based practice implementation Gregory A. Aarons, Amy E. Green, Mark. G. Ehrhart, Elise M. Trott, Cathleen E. Willging A4: Implementing practice change in Federally Qualified Health Centers: Learning from leaders’ experiences Maria E. Fernandez, Nicholas H. Woolf, Shuting (Lily) Liang, Natalia I. Heredia, Michelle Kegler, Betsy Risendal, Andrea Dwyer, Vicki Young, Dayna Campbell, Michelle Carvalho, Yvonne Kellar-Guenther A3: Mixed method examination of strategic leadership for evidence-based practice implementation Gregory A. Aarons, Amy E. Green, Mark. G. Ehrhart, Elise M. Trott, Cathleen E. Willging A4: Implementing practice change in Federally Qualified Health Centers: Learning from leaders’ experiences Maria E. Fernandez, Nicholas H. Woolf, Shuting (Lily) Liang, Natalia I. Heredia, Michelle Kegler, Betsy Risendal, Andrea Dwyer, Vicki Young, Dayna Campbell, Michelle Carvalho, Yvonne Kellar-Guenther A5: Efficient synthesis: Using qualitative comparative analysis and the Consolidated Framework for Implementation Research across diverse studies Laura J. Damschroder, Julie C. Lowery A6: Establishing a veterans engagement group to empower patients and inform Veterans Affairs (VA) health services research Sarah S. Ono, Kathleen F. Carlson, Erika K. Cottrell, Maya E. O’Neil, Travis L. Lovejoy A7: Building patient-practitioner partnerships in community oncology settings to implement behavioral interventions for anxious and depressed cancer survivors Joanna J. Arch, Jill L. Mitchell A8: Tailoring a Cognitive Behavioral Therapy implementation protocol using mixed methods, conjoint analysis, and implementation teams Cara C. Lewis, Brigid R. Marriott, Kelli Scott A9: Wraparound Structured Assessment and Review (WrapSTAR): An efficient, yet comprehensive approach to Wraparound implementation evaluation Jennifer Schurer Coldiron, Eric J. Bruns, Alyssa N. Hook A10: Improving the efficiency of standardized patient assessment of clinician fidelity: A comparison of automated actor-based and manual clinician-based ratings Benjamin C. Graham, Katelin Jordan A11: Measuring fidelity on the cheap Rochelle F. Hanson, Angela Moreland, Benjamin E. Saunders, Heidi S. Resnick A12: Leveraging routine clinical materials to assess fidelity to an evidence-based psychotherapy Shannon Wiltsey Stirman, Cassidy A. Gutner, Jennifer Gamarra, Dawne Vogt, Michael Suvak, Jennifer Schuster Wachen, Katherine Dondanville, Jeffrey S. Yarvis, Jim Mintz, Alan L. Peterson, Elisa V. Borah, Brett T. Litz, Alma Molino, Stacey Young McCaughanPatricia A. Resick A13: The video vignette survey: An efficient process for gathering diverse community opinions to inform an intervention Nancy Pandhi, Nora Jacobson, Neftali Serrano, Armando Hernandez, Elizabeth Zeidler- Schreiter, Natalie Wietfeldt, Zaher Karp A14: Using integrated administrative data to evaluate implementation of a behavioral health and trauma screening for children and youth in foster care Michael D. Pullmann, Barbara Lucenko, Bridget Pavelle, Jacqueline A. Uomoto, Andrea Negrete, Molly Cevasco, Suzanne E. U. Kerns A15: Intermediary organizations as a vehicle to promote efficiency and speed of implementation Robert P. Franks, Christopher Bory A16: Applying the Consolidated Framework for Implementation Research constructs directly to qualitative data: The power of implementation science in action Edward J. Miech, Teresa M. Damush A17: Efficient and effective scaling-up, screening, brief interventions, and referrals to treatment (SBIRT) training: a snowball implementation model Jason Satterfield, Derek Satre, Maria Wamsley, Patrick Yuan, Patricia O’Sullivan A18: Matching models of implementation to system needs and capacities: addressing the human factor Helen Best, Susan Velasquez A19: Agency characteristics that facilitate efficient and successful implementation efforts Miya Barnett, Lauren Brookman-Frazee, Jennifer Regan, Nicole Stadnick, Alison Hamilton, Anna Lau A20: Rapid assessment process: Application to the Prevention and Early Intervention transformation in Los Angeles County Jennifer Regan, Alison Hamilton, Nicole Stadnick, Miya Barnett, Anna Lau, Lauren Brookman-Frazee A21: The development of the Evidence-Based Practice-Concordant Care Assessment: An assessment tool to examine treatment strategies across practices Nicole Stadnick, Anna Lau, Miya Barnett, Jennifer Regan, Scott Roesch, Lauren Brookman-Frazee A22: Refining a compilation of discrete implementation strategies and determining their importance and feasibility Byron J. Powell, Thomas J. Waltz, Matthew J. Chinman, Laura Damschroder, Jeffrey L. Smith, Monica M. Matthieu, Enola K. Proctor, JoAnn E. Kirchner A23: Structuring complex recommendations: Methods and general findings Thomas J. Waltz, Byron J. Powell, Matthew J. Chinman, Laura J. Damschroder, Jeffrey L. Smith, Monica J. Matthieu, Enola K. Proctor, JoAnn E. Kirchner A24: Implementing prolonged exposure for post-traumatic stress disorder in the Department of Veterans Affairs: Expert recommendations from the Expert Recommendations for Implementing Change (ERIC) project Monica M. Matthieu, Craig S. Rosen, Thomas J. Waltz, Byron J. Powell, Matthew J. Chinman, Laura J. Damschroder, Jeffrey L. Smith, Enola K. Proctor, JoAnn E. Kirchner A25: When readiness is a luxury: Co-designing a risk assessment and quality assurance process with violence prevention frontline workers in Seattle, WA Sarah C. Walker, Asia S. Bishop, Mariko Lockhart A26: Implementation potential of structured recidivism risk assessments with justice- involved veterans: Qualitative perspectives from providers Allison L. Rodriguez, Luisa Manfredi, Andrea Nevedal, Joel Rosenthal, Daniel M. Blonigen A27: Developing empirically informed readiness measures for providers and agencies for the Family Check-Up using a mixed methods approach Anne M. Mauricio, Thomas D. Dishion, Jenna Rudo-Stern, Justin D. Smith A28: Pebbles, rocks, and boulders: The implementation of a school-based social engagement intervention for children with autism Jill Locke, Courtney Benjamin Wolk, Colleen Harker, Anne Olsen, Travis Shingledecker, Frances Barg, David Mandell, Rinad S. Beidas A29: Problem Solving Teletherapy (PST.Net): A stakeholder analysis examining the feasibility and acceptability of teletherapy in community based aging services Marissa C. Hansen, Maria P. Aranda, Isabel Torres-Vigil A30: A case of collaborative intervention design eventuating in behavior therapy sustainment and diffusion Bryan Hartzler A31: Implementation of suicide risk prevention in an integrated delivery system: Mental health specialty services Bradley Steinfeld, Tory Gildred, Zandrea Harlin, Fredric Shephard A32: Implementation team, checklist, evaluation, and feedback (ICED): A step-by-step approach to Dialectical Behavior Therapy program implementation Matthew S. Ditty, Andrea Doyle, John A. Bickel III, Katharine Cristaudo A33: The challenges in implementing muliple evidence-based practices in a community mental health setting Dan Fox, Sonia Combs A34: Using electronic health record technology to promote and support evidence-based practice assessment and treatment intervention David H. Lischner A35: Are existing frameworks adequate for measuring implementation outcomes? Results from a new simulation methodology Richard A. Van Dorn, Stephen J. Tueller, Jesse M. Hinde, Georgia T. Karuntzos A36: Taking global local: Evaluating training of Washington State clinicians in a modularized cogntive behavioral therapy approach designed for low-resource settings Maria Monroe-DeVita, Roselyn Peterson, Doyanne Darnell, Lucy Berliner, Shannon Dorsey, Laura K. Murray A37: Attitudes toward evidence-based practices across therapeutic orientations Yevgeny Botanov, Beverly Kikuta, Tianying Chen, Marivi Navarro-Haro, Anthony DuBose, Kathryn E. Korslund, Marsha M. Linehan A38: Predicting the use of an evidence-based intervention for autism in birth-to-three programs Colleen M. Harker, Elizabeth A. Karp, Sarah R. Edmunds, Lisa V. Ibañez, Wendy L. Stone A39: Supervision practices and improved fidelity across evidence-based practices: A literature review Mimi Choy-Brown A40: Beyond symptom tracking: clinician perceptions of a hybrid measurement feedback system for monitoring treatment fidelity and client progress Jack H. Andrews, Benjamin D. Johnides, Estee M. Hausman, Kristin M. Hawley A41: A guideline decision support tool: From creation to implementation Beth Prusaczyk, Alex Ramsey, Ana Baumann, Graham Colditz, Enola K. Proctor A42: Dabblers, bedazzlers, or total makeovers: Clinician modification of a common elements cognitive behavioral therapy approach Rosemary D. Meza, Shannon Dorsey, Shannon Wiltsey-Stirman, Georganna Sedlar, Leah Lucid A43: Characterization of context and its role in implementation: The impact of structure, infrastructure, and metastructure Caitlin Dorsey, Brigid Marriott, Nelson Zounlome, Cara Lewis A44: Effects of consultation method on implementation of cognitive processing therapy for post-traumatic stress disorder Cassidy A. Gutner, Candice M. Monson, Norman Shields, Marta Mastlej, Meredith SH Landy, Jeanine Lane, Shannon Wiltsey Stirman A45: Cross-validation of the Implementation Leadership Scale factor structure in child welfare service organizations Natalie K. Finn, Elisa M. Torres, Mark. G. Ehrhart, Gregory A. Aarons A46: Sustainability of integrated smoking cessation care in Veterans Affairs posttraumatic stress disorder clinics: A qualitative analysis of focus group data from learning collaborative participants Carol A. Malte, Aline Lott, Andrew J. Saxon A47: Key characteristics of effective mental health trainers: The creation of the Measure of Effective Attributes of Trainers (MEAT) Meredith Boyd, Kelli Scott, Cara C. Lewis A48: Coaching to improve teacher implementation of evidence-based practices (EBPs) Jennifer D. Pierce A49: Factors influencing the implementation of peer-led health promotion programs targeting seniors: A literature review Agathe Lorthios-Guilledroit, Lucie Richard, Johanne Filiatrault A50: Developing treatment fidelity rating systems for psychotherapy research: Recommendations and lessons learned Kevin Hallgren, Shirley Crotwell, Rosa Muñoz, Becky Gius, Benjamin Ladd, Barbara McCrady, Elizabeth Epstein A51: Rapid translation of alcohol prevention science John D. Clapp, Danielle E. Ruderman A52: Factors implicated in successful implementation: evidence to inform improved implementation from high and low-income countries Melanie Barwick, Raluca Barac, Stanley Zlotkin, Laila Salim, Marnie Davidson A53: Tracking implementation strategies prospectively: A practical approach Alicia C. Bunger, Byron J. Powell, Hillary A. Robertson A54: Trained but not implementing: the need for effective implementation planning tools Christopher Botsko A55: Evidence, context, and facilitation variables related to implementation of Dialectical Behavior Therapy: Qualitative results from a mixed methods inquiry in the Department of Veterans Affairs Sara J. Landes, Brandy N. Smith, Allison L. Rodriguez, Lindsay R. Trent, Monica M. Matthieu A56: Learning from implementation as usual in children’s mental health Byron J. Powell, Enola K. Proctor A57: Rates and predictors of implementation after Dialectical Behavior Therapy Intensive Training Melanie S. Harned, Marivi Navarro-Haro, Kathryn E. Korslund, Tianying Chen, Anthony DuBose, André Ivanoff, Marsha M. Linehan A58: Socio-contextual determinants of research evidence use in public-youth systems of care Antonio R. Garcia, Minseop Kim, Lawrence A. Palinkas, Lonnie Snowden, John Landsverk A59: Community resource mapping to integrate evidence-based depression treatment in primary care in Brazil: A pilot project Annika C. Sweetland, Maria Jose Fernandes, Edilson Santos, Cristiane Duarte, Afrânio Kritski, Noa Krawczyk, Caitlin Nelligan, Milton L. Wainberg A60: The use of concept mapping to efficiently identify determinants of implementation in the National Institute of Health--President’s Emergent Plan for AIDS Relief Prevention of Mother to Child HIV Transmission Implementation Science Alliance Gregory A. Aarons, David H. Sommerfeld, Benjamin Chi, Echezona Ezeanolue, Rachel Sturke, Lydia Kline, Laura Guay, George Siberry A61: Longitudinal remote consultation for implementing collaborative care for depression Ian M. Bennett, Rinad Beidas, Rachel Gold, Johnny Mao, Diane Powers, Mindy Vredevoogd, Jurgen Unutzer A62: Integrating a peer coach model to support program implementation and ensure long- term sustainability of the Incredible Years in community-based settings Jennifer Schroeder, Lane Volpe, Julie Steffen A63: Efficient sustainability: Existing community based supervisors as evidence-based treatment supports Shannon Dorsey, Michael D Pullmann, Suzanne E. U. Kerns, Nathaniel Jungbluth, Lucy Berliner, Kelly Thompson, Eliza Segell A64: Establishment of a national practice-based implementation network to accelerate adoption of evidence-based and best practices Pearl McGee-Vincent, Nancy Liu, Robyn Walser, Jennifer Runnals, R. Keith Shaw, Sara J. Landes, Craig Rosen, Janet Schmidt, Patrick Calhoun A65: Facilitation as a mechanism of implementation in a practice-based implementation network: Improving care in a Department of Veterans Affairs post-traumatic stress disorder outpatient clinic Ruth L. Varkovitzky, Sara J. Landes A66: The ACT SMART Toolkit: An implementation strategy for community-based organizations providing services to children with autism spectrum disorder Amy Drahota, Jonathan I. Martinez, Brigitte Brikho, Rosemary Meza, Aubyn C. Stahmer, Gregory A. Aarons A67: Supporting Policy In Health with Research: An intervention trial (SPIRIT) - protocol and early findings Anna Williamson A68: From evidence based practice initiatives to infrastructure: Lessons learned from a public behavioral health system’s efforts to promote evidence based practices Ronnie M. Rubin, Byron J. Powell, Matthew O. Hurford, Shawna L. Weaver, Rinad S. Beidas, David S. Mandell, Arthur C. Evans A69: Applying the policy ecology model to Philadelphia’s behavioral health transformation efforts Byron J. Powell, Rinad S. Beidas, Ronnie M. Rubin, Rebecca E. Stewart, Courtney Benjamin Wolk, Samantha L. Matlin, Shawna Weaver, Matthew O. Hurford, Arthur C. Evans, Trevor R. Hadley, David S. Mandell A70: A model for providing methodological expertise to advance dissemination and implementation of health discoveries in Clinical and Translational Science Award institutions Donald R. Gerke, Beth Prusaczyk, Ana Baumann, Ericka M. Lewis, Enola K. Proctor A71: Establishing a research agenda for the Triple P Implementation Framework Jenna McWilliam, Jacquie Brown, Michelle Tucker A72: Cheap and fast, but what is “best?”: Examining implementation outcomes across sites in a state-wide scaled-up evidence-based walking program, Walk With Ease Kathleen P Conte A73: Measurement feedback systems in mental health: Initial review of capabilities and characteristics Aaron R. Lyon, Meredith Boyd, Abigail Melvin, Cara C. Lewis, Freda Liu, Nathaniel Jungbluth A74: A qualitative investigation of case managers’ attitudes toward implementation of a measurement feedback system in a public mental health system for youth Amelia Kotte, Kaitlin A. Hill, Albert C. Mah, Priya A. Korathu-Larson, Janelle R. Au, Sonia Izmirian, Scott Keir, Brad J. Nakamura, Charmaine K. Higa-McMillan A75: Multiple pathways to sustainability: Using Qualitative Comparative Analysis to uncover the necessary and sufficient conditions for successful community-based implementation Brittany Rhoades Cooper, Angie Funaiole, Eleanor Dizon A76: Prescribers’ perspectives on opioids and benzodiazepines and medication alerts to reduce co-prescribing of these medications Eric J. Hawkins, Carol A. Malte, Hildi J. Hagedorn, Douglas Berger, Anissa Frank, Aline Lott, Carol E. Achtmeyer, Anthony J. Mariano, Andrew J. Saxon A77: Adaptation of Coordinated Anxiety Learning and Management for comorbid anxiety and substance use disorders: Delivery of evidence-based treatment for anxiety in addictions treatment centers Kate Wolitzky-Taylor, Richard Rawson, Richard Ries, Peter Roy-Byrne, Michelle Craske A78: Opportunities and challenges of measuring program implementation with online surveys Dena Simmons, Catalina Torrente, Lori Nathanson, Grace Carroll A79: Observational assessment of fidelity to a family-centered prevention program: Effectiveness and efficiency Justin D. Smith, Kimbree Brown, Karina Ramos, Nicole Thornton, Thomas J. Dishion, Elizabeth A. Stormshak, Daniel S. Shaw, Melvin N. Wilson A80: Strategies and challenges in housing first fidelity: A multistate qualitative analysis Mimi Choy-Brown, Emmy Tiderington, Bikki Tran Smith, Deborah K. Padgett A81: Procurement and contracting as an implementation strategy: Getting To Outcomes® contracting Ronnie M. Rubin, Marilyn L. Ray, Abraham Wandersman, Andrea Lamont, Gordon Hannah, Kassandra A. Alia, Matthew O. Hurford, Arthur C. Evans A82: Web-based feedback to aid successful implementation: The interactive Stages of Implementation Completion (SIC)TM tool Lisa Saldana, Holle Schaper, Mark Campbell, Patricia Chamberlain A83: Efficient methodologies for monitoring fidelity in routine implementation: Lessons from the Allentown Social Emotional Learning Initiative Valerie B. Shapiro, B.K. Elizabeth Kim, Jennifer L. Fleming, Paul A. LeBuffe A84: The Society for Implementation Research Collaboration (SIRC) implementation development workshop: Results from a new methodology for enhancing implementation science proposals Sara J. Landes, Cara C. Lewis, Allison L. Rodriguez, Brigid R. Marriott, Katherine Anne Comtois A85: An update on the Society for Implementation Research Collaboration (SIRC) Instrument Review Projec

Assessing changes in global fire regimes

PAGES, Past Global Changes, is funded by the Swiss Academy of Sciences and the Chinese Academy of Sciences and supported in kind by the University of Bern, Switzerland. Financial support was provided by the U.S. National Science Foundation award numbers 1916565, EAR-2011439, and EAR-2012123. Additional support was provided by the Utah Department of Natural Resources Watershed Restoration Initiative. SSS was supported by Brigham Young University Graduate Studies. MS was supported by National Science Centre, Poland (grant no. 2018/31/B/ST10/02498 and 2021/41/B/ST10/00060). JCA was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 101026211. PF contributed within the framework of the FCT-funded project no. UIDB/04033/2020. SGAF acknowledges support from Trond Mohn Stiftelse (TMS) and University of Bergen for the startup grant ‘TMS2022STG03’. JMP participation in this research was supported by the Forest Research Centre, a research unit funded by Fundação para a Ciência e a Tecnologia I.P. (FCT), Portugal (UIDB/00239/2020). A.-LD acknowledge PAGES, PICS CNRS 06484 project, CNRS-INSU, Région Nouvelle-Aquitaine, University of Bordeaux DRI and INQUA for workshop support.Background The global human footprint has fundamentally altered wildfire regimes, creating serious consequences for human health, biodiversity, and climate. However, it remains difficult to project how long-term interactions among land use, management, and climate change will affect fire behavior, representing a key knowledge gap for sustainable management. We used expert assessment to combine opinions about past and future fire regimes from 99 wildfire researchers. We asked for quantitative and qualitative assessments of the frequency, type, and implications of fire regime change from the beginning of the Holocene through the year 2300. Results Respondents indicated some direct human influence on wildfire since at least ~ 12,000 years BP, though natural climate variability remained the dominant driver of fire regime change until around 5,000 years BP, for most study regions. Responses suggested a ten-fold increase in the frequency of fire regime change during the last 250 years compared with the rest of the Holocene, corresponding first with the intensification and extensification of land use and later with anthropogenic climate change. Looking to the future, fire regimes were predicted to intensify, with increases in frequency, severity, and size in all biomes except grassland ecosystems. Fire regimes showed different climate sensitivities across biomes, but the likelihood of fire regime change increased with higher warming scenarios for all biomes. Biodiversity, carbon storage, and other ecosystem services were predicted to decrease for most biomes under higher emission scenarios. We present recommendations for adaptation and mitigation under emerging fire regimes, while recognizing that management options are constrained under higher emission scenarios. Conclusion The influence of humans on wildfire regimes has increased over the last two centuries. The perspective gained from past fires should be considered in land and fire management strategies, but novel fire behavior is likely given the unprecedented human disruption of plant communities, climate, and other factors. Future fire regimes are likely to degrade key ecosystem services, unless climate change is aggressively mitigated. Expert assessment complements empirical data and modeling, providing a broader perspective of fire science to inform decision making and future research priorities.Peer reviewe

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Engineering Virus-Mimicking Protein Nanoparticles for Cancer Immunotherapy

The immune system represents a powerful resource for the eradication of cancer. To harness the full potential of this sophisticated network to overcome the low immunogenicity of tumor cells, a sufficiently strong cytotoxic CD8 T cell (CTL)-mediated adaptive immune response is required, which is partly orchestrated by the professional antigen presenting cells of the innate immune system, most notably the dendritic cell (DC). Protein nanoparticles represent a potentially exceptional vaccination platform for cancer, as they have the ability to mimic viral infections, which are known potent inducers of CTL immunity. We have been exploring the E2 protein nanoparticle as a delivery platform for antigens and immune-stimulating compounds. The E2 nanoparticle was successfully packaged internally with endolysosomal-releasable immune-activating DNA (CpG) and surface functionalized with MHC I-restricted peptide epitopes. The virus-mimicking nanoparticle induced DC activation at a 25-fold lower concentration compared to free CpG and induced a 3-fold increase in cross-presentation of attached epitopes, compared to free forms of peptides or activators. Furthermore, we demonstrated that co-delivery of melanoma-associated epitopes and immune-activating CpG with E2 enhanced antigen specific CTL proliferation index by 1.5-fold with a concomitant 5-fold increase in IFN-γ cytokine secretion, compared to unbound peptide and CpG. Remarkably, a single immunization with the multifunctional E2 nanoparticle increased the frequency of melanoma-specific CTL in vivo (120-fold increase in the lymph node and 30-fold increase in the spleen) and the CTL generated showed approximately three times the lytic capacity toward a gp100-expressing melanoma cell line, compared to unbound peptide and CpG immunization. We were also able to tune cellular and immunological interactions toward the E2 nanoparticle with surface display of poly(ethylene glycol) polymers, where PEGylation through various methods (native surface amines or a recombinantly introduced cysteine) was shown to decrease cell uptake by greater than 50% of both mouse and human cell lines. PEGylation was also shown to mediate moderate increases in complement activation (~35% C5a production, compared to a known activator), a humoral innate immune mechanism, whereas E2 itself did not cause complement activation. Surface display of CpG on PEGylated E2 nanoparticles was shown to specifically increase cellular uptake by antigen presenting cells. Fluorescently-labelled E2 was shown to preferentially drain to the lymph nodes after subcutaneous administration, and surface PEGylation allowed further diffusion to more distal locations and blood draining organs. In contrast, surface display of CpG caused increased proximal lymph node accumulation, and demonstrated superior retention, with ~ 10-fold increase in LN fluorescence after 48 hours over the other nanoparticles. Within the lymph nodes, ~50% of the nanoparticles were associated with antigen presenting cells, including dendritic cells. Altogether, our results demonstrate the potential of the E2 protein nanoparticle as a versatile virus-mimicking immunomodulatory cancer vaccine platform. We have developed a nanoparticle biomaterial for DC-targeting, lymph node retention, and superior induction of CTL-mediated responses against cancer