Spectrum of cellular responses to pyriplatin, a monofunctional cationic antineoplastic platinum(II) compound, in human cancer cells

Pyriplatin, cis-diammine(pyridine)chloroplatinum(II), a platinum-based antitumor drug candidate, is a cationic compound with anticancer properties in mice and is a substrate for organic cation transporters that facilitate oxaliplatin uptake. Unlike cisplatin and oxaliplatin, which form DNA cross-links, pyriplatin binds DNA in a monofunctional manner. The antiproliferative effects of pyriplatin, alone and in combination with known anticancer drugs (paclitaxel, gemcitabine, SN38, cisplatin, and 5-fluorouracil), were evaluated in a panel of epithelial cancer cell lines, with direct comparison to cisplatin and oxaliplatin. The effects of pyriplatin on gene expression and platinum–DNA adduct formation were also investigated. Pyriplatin exhibited cytotoxic effects against human cell lines after 24 hours (IC[subscript 50] = 171–443 μmol/L), with maximum cytotoxicity in HOP-62 non–small cell lung cancer cells after 72 hours (IC[subscript 50] = 24 μmol/L). Pyriplatin caused a G[subscript 2]-M cell cycle block similar to that induced by cisplatin and oxaliplatin. Induction of apoptotsis and DNA damage response was supported by Annexin-V analysis and detection of phosphorylated Chk2 and H2AX. Treatment with pyriplatin increased CDKN1/p21 and decreased ERCC1 mRNA expression. On a platinum-per-nucleotide basis, pyriplatin–DNA adducts are less cytotoxic than those of cisplatin and oxaliplatin. The mRNA levels of genes implicated in drug transport and DNA damage repair, including GSTP1 and MSH2, correlate with pyriplatin cellular activity in the panel of cell lines. Synergy occurred for combinations of pyriplatin with paclitaxel. Because its spectrum of activity differs significantly from those of cisplatin or oxaliplatin, pyriplatin is a lead compound for developing novel drug candidates with cytotoxicity profiles unlike those of drugs currently in use

Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.National Institutes of Health (U.S.) (grant 5-UO1-CA84306)National Cancer Institute (U.S.) (CA034992

Non-traditional platinum compounds for improved accumulation, oral bioavailability, and tumor targeting

The five platinum anticancer compounds currently in clinical use conform to structure–activity relationships formulated (M. J. Cleare and J. D. Hoeschele, Bioinorg. Chem., 1973, 2, 187–210) shortly after the discovery that cis-diamminedichloroplatinum(II), cisplatin, has antitumor activity in mice. These compounds are neutral platinum(II) species with two am(m)ine ligands or one bidentate chelating diamine and two additional ligands that can be replaced by water through aquation reactions. The resulting cations ultimately form bifunctional adducts on DNA. Information about the chemistry of these platinum compounds and correlations of their structures with anticancer activity have provided guidance for the design of novel anticancer drug candidates based on the proposed mechanisms of action. This article discusses advances in the synthesis and evaluation of such non-traditional platinum compounds, including cationic and tumor-targeting constructs.National Cancer Institute (U.S.) (Grant CA34992

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

The dental calculus metabolome in modern and historic samples.

INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. OBJECTIVE: We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. CONCLUSIONS: The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies

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

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests. Resumen Los bosques tropicales son los ecosistemas más diversos y productivos del mundo y entender su funcionamiento es crítico para nuestro futuro colectivo. Sin embargo, hasta hace muy poco, los esfuerzos para medirlos y monitorearlos han estado muy desconectados. El trabajo en redes es esencial para descubrir las respuestas a preguntas que trascienden las fronteras y los plazos de las agencias de financiamiento. Aquí mostramos cómo una comunidad global está respondiendo a los desafíos de la investigación en ecosistemas tropicales a través de diversos equipos realizando mediciones árbol por árbol en miles de parcelas permanentes de largo plazo. Revisamos los descubrimientos más importantes de este trabajo y discutimos cómo este proceso está cambiando la ciencia relacionada a los bosques tropicales. El enfoque central de nuestro esfuerzo implica la conexión de iniciativas locales de largo plazo con protocolos estandarizados y manejo de datos para producir resultados que se puedan trasladar a múltiples escalas. Conectando investigadores tropicales, elevando su posición y estatus, nuestro modelo de Red Social de Investigación reconoce el rol fundamental que tienen, para el descubrimiento científico, quienes generan o producen los datos. Concebida en 1999 con RAINFOR (Suramérica), nuestras redes de parcelas permanentes han sido adaptadas en África (AfriTRON) y el sureste asiático (T-FORCES) y ampliamente replicadas en el mundo. Actualmente todas estas iniciativas están integradas a través de la ciber-infraestructura de ForestPlots.net, conectando colegas de 54 países en 24 redes diferentes de parcelas. Colectivamente, estas redes están transformando nuestro conocimiento sobre los bosques tropicales y el rol de éstos en la biósfera. Juntos hemos descubierto cómo, dónde y porqué el carbono y la biodiversidad de los bosques tropicales está respondiendo al cambio climático y cómo se retroalimentan. Esta colaboración pan-tropical de largo plazo ha expuesto un gran sumidero de carbono y sus tendencias, mostrando claramente cuáles son los factores más importantes, qué procesos se ven afectados, dónde ocurren los cambios, los tiempos de reacción y las probables respuestas futuras mientras el clima continúa cambiando. Apalancando lo que realmente es una tecnología antigua, las redes de parcelas están generando una verdadera y moderna revolución en la ciencia tropical. En el futuro, la humanidad puede beneficiarse enormemente si se nutren y cultivan comunidades de investigadores de base, actualmente con la capacidad de generar información única y de largo plazo para entender los que probablemente son los bosques más preciados de la tierra. Resumo Florestas tropicais são os ecossistemas mais diversos e produtivos da Terra. Embora uma boa compreensão destas florestas seja crucial para o nosso futuro coletivo, até muito recentemente os esforços de medições e monitoramento foram amplamente desconexos. É essencial formarmos redes para obtermos respostas que transcendem fronteiras e horizontes de agências financiadoras. Neste estudo nós mostramos como uma comunidade global está respondendo aos desafios da pesquisa de ecossistemas tropicais, com equipes diversas medindo florestas, árvore por árvore, em milhares de parcelas monitoradas à longo prazo. Nós revisamos as maiores descobertas científicas deste trabalho, e mostramos também como este processo está mudando a ciência de florestas tropicais. Nossa abordagem principal envolve unir iniciativas de base a protocolos padronizados e gerenciamento de dados a fim de gerar resultados robustos em escalas ampliadas. Ao conectar pesquisadores tropicais e elevar seus status, nosso modelo de Rede de Pesquisa Social reconhece o papel-chave do produtor dos dados na descoberta científica. Concebida em 1999 com o RAINFOR (América do Sul), nossa rede de parcelas permanentes foi adaptada para África (AfriTRON) e Sudeste asiático (T-FORCES), e tem sido extensamente reproduzida em todo o mundo. Agora estas múltiplas iniciativas estão integradas através de uma infraestrutura cibernética do ForestPlots.net, conectando colegas de 54 países de 24 redes de parcelas. Estas iniciativas estão transformando coletivamente o entendimento das florestas tropicais e seus papéis na biosfera. Juntos nós descobrimos como, onde e por que o carbono e a biodiversidade da floresta estão respondendo às mudanças climáticas, e seus efeitos de retroalimentação. Esta duradoura colaboração pantropical revelou um grande sumidouro de carbono persistente e suas tendências, assim como tem evidenciado quais direcionadores são mais importantes, quais processos florestais são mais afetados, onde eles estão mudando, seus atrasos no tempo de resposta, e as prováveis respostas das florestas tropicais conforme o clima continua a mudar. Dessa forma, aproveitando uma notável tecnologia antiga, redes de parcelas acendem faíscas de uma moderna revolução na ciência das florestas tropicais. No futuro a humanidade pode se beneficiar incentivando estas comunidades basais que agora são coletivamente capazes de gerar conhecimentos únicos e duradouros sobre as florestas mais preciosas da Terra. Résume Les forêts tropicales sont les écosystèmes les plus diversifiés et les plus productifs de la planète. Si une meilleure compréhension de ces forêts est essentielle pour notre avenir collectif, jusqu'à tout récemment, les efforts déployés pour les mesurer et les surveiller ont été largement déconnectés. La mise en réseau est essentielle pour découvrir les réponses à des questions qui dépassent les frontières et les horizons des organismes de financement. Nous montrons ici comment une communauté mondiale relève les défis de la recherche sur les écosystèmes tropicaux avec diverses équipes qui mesurent les forêts arbre après arbre dans de milliers de parcelles permanentes. Nous passons en revue les principales découvertes scientifiques de ces travaux et montrons comment ce processus modifie la science des forêts tropicales. Notre approche principale consiste à relier les initiatives de base à long terme à des protocoles standardisés et une gestion de données afin de générer des résultats solides à grande échelle. En reliant les chercheurs tropicaux et en élevant leur statut, notre modèle de réseau de recherche sociale reconnaît le rôle clé de l'auteur des données dans la découverte scientifique. Conçus en 1999 avec RAINFOR (Amérique du Sud), nos réseaux de parcelles permanentes ont été adaptés à l'Afrique (AfriTRON) et à l'Asie du Sud-Est (T-FORCES) et largement imités dans le monde entier. Ces multiples initiatives sont désormais intégrées via l'infrastructure ForestPlots.net, qui relie des collègues de 54 pays à travers 24 réseaux de parcelles. Ensemble, elles transforment la compréhension des forêts tropicales et de leur rôle biosphérique. Ensemble, nous avons découvert comment, où et pourquoi le carbone forestier et la biodiversité réagissent au changement climatique, et comment ils y réagissent. Cette collaboration pan-tropicale à long terme a révélé un important puits de carbone à long terme et ses tendances, tout en mettant en évidence les facteurs les plus importants, les processus forestiers qui sont affectés, les endroits où ils changent, les décalages et les réactions futures probables des forêts tropicales à mesure que le climat continue de changer. En tirant parti d'une technologie remarquablement ancienne, les réseaux de parcelles déclenchent une révolution très moderne dans la science des forêts tropicales. À l'avenir, l'humanité pourra grandement bénéficier du soutien des communautés de base qui sont maintenant collectivement capables de générer une compréhension unique et à long terme des forêts les plus précieuses de la Terre. Abstrak Hutan tropika adalah di antara ekosistem yang paling produktif dan mempunyai kepelbagaian biodiversiti yang tinggi di seluruh dunia. Walaupun pemahaman mengenai hutan tropika amat penting untuk masa depan kita, usaha-usaha untuk mengkaji dan mengawas hutah-hutan tersebut baru sekarang menjadi lebih diperhubungkan. Perangkaian adalah sangat penting untuk mencari jawapan kepada soalan-soalan yang menjangkaui sempadan dan batasan agensi pendanaan. Di sini kami menunjukkan bagaimana sebuah komuniti global bertindak balas terhadap cabaran penyelidikan ekosistem tropika melalui penglibatan pelbagai kumpulan yang mengukur hutan secara pokok demi pokok dalam beribu-ribu plot jangka panjang. Kami meninjau semula penemuan saintifik utama daripada kerja ini dan menunjukkan bagaimana proses ini sedang mengubah bidang sains hutan tropika. Teras pendekatan kami memberi tumpuan terhadap penghubungan inisiatif akar umbi jangka panjang dengan protokol standar serta pengurusan data untuk mendapatkan hasil skala besar yang kukuh. Dengan menghubungkan penyelidik-penyelidik tropika dan meningkatkan status mereka, model Rangkaian Penyelidikan Sosial kami mengiktiraf kepentingan peranan pengasas data dalam penemuan saintifik. Bermula dengan pengasasan RAINFOR (Amerika Selatan) pada tahun 1999, rangkaian-rangkaian plot kekal kami kemudian disesuaikan untuk Afrika (AfriTRON) dan Asia Tenggara (T-FORCES) dan selanjutnya telah banyak dicontohi di seluruh dunia. Kini, inisiatif-inisiatif tersebut disepadukan melalui infrastruktur siber ForestPlots.net yang menghubungkan rakan sekerja dari 54 negara di 24 buah rangkaian plot. Secara kolektif, rangkaian ini sedang mengubah pemahaman tentang hutan tropika dan peranannya dalam biosfera. Kami telah bekerjasama untuk menemukan bagaimana, di mana dan mengapa karbon serta biodiversiti hutan bertindak balas terhadap perubahan iklim dan juga bagaimana mereka saling bermaklum balas. Kolaborasi pan-tropika jangka panjang ini telah mendedahkan sebuah sinki karbon jangka panjang serta arah alirannya dan juga menjelaskan pemandu-pemandu perubahan yang terpenting, di mana dan bagaimana proses hutan terjejas, masa susul yang ada dan kemungkinan tindakbalas hutan tropika pada perubahan iklim secara berterusan di masa depan. Dengan memanfaatkan pendekatan lama, rangkaian plot sedang menyalakan revolusi yang amat moden dalam sains hutan tropika. Pada masa akan datang, manusia sejagat akan banyak mendapat manfaat jika memupuk komuniti-komuniti akar umbi yang kini berkemampuan secara kolektif menghasilkan pemahaman unik dan jangka panjang mengenai hutan-hutan yang paling berharga di dunia