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 state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Ecosystem resilience despite large-scale altered hydroclimatic conditions

Climate change is predicted to increase both drought frequency and duration, and when coupled with substantial warming, will establish a new hydroclimatological model for many regions. Large-scale, warm droughts have recently occurred in North America, Africa, Europe, Amazonia and Australia, resulting in major effects on terrestrial ecosystems, carbon balance and food security. Here we compare the functional response of above-ground net primary production to contrasting hydroclimatic periods in the late twentieth century (1975-1998), and drier, warmer conditions in the early twenty-first century (2000-2009) in the Northern and Southern Hemispheres. We find a common ecosystem water-use efficiency (WUE e: Above-ground net primary production/ evapotranspiration) across biomes ranging from grassland to forest that indicates an intrinsic system sensitivity to water availability across rainfall regimes, regardless of hydroclimatic conditions. We found higher WUE e in drier years that increased significantly with drought to a maximum WUE e across all biomes; and a minimum native state in wetter years that was common across hydroclimatic periods. This indicates biome-scale resilience to the interannual variability associated with the early twenty-first century drought - that is, the capacity to tolerate low, annual precipitation and to respond to subsequent periods of favourable water balance. These findings provide a conceptual model of ecosystem properties at the decadal scale applicable to the widespread altered hydroclimatic conditions that are predicted for later this century. Understanding the hydroclimatic threshold that will break down ecosystem resilience and alter maximum WUE e may allow us to predict land-surface consequences as large regions become more arid, starting with water-limited, low-productivity grasslands. © 2013 Macmillan Publishers Limited. All rights reserved

A pre-registered, multi-lab non-replication of the Action-sentence Compatibility Effect (ACE)

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.Fil: Morey, Richard. Cardiff University; Reino UnidoFil: Kaschak, Michael. Florida State University; Estados UnidosFil: Díez Álamo, Antonio. Universidad de Salamanca; España. Arizona State University; Estados UnidosFil: Glenberg, Arthur. Arizona State University; Estados Unidos. Universidad de Salamanca; EspañaFil: Zwaan, Rolf A.. Erasmus University Rotterdam; Países BajosFil: Lakens, Daniël. Eindhoven University of Technology; Países BajosFil: Ibáñez, Santiago Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of San Francisco; Estados Unidos. Universidad Adolfo Ibañez; Chile. Trinity College Dublin; IrlandaFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina. University of San Francisco; Estados Unidos. Universidad Nacional de Cuyo. Facultad de Educación Elemental y Especial; Argentina. Universidad de Santiago de Chile; ChileFil: Gianelli, Claudia. Universitat Potsdam; Alemania. Scuola Universitaria Superiore; ItaliaFil: Jones, John L.. Florida State University; Estados UnidosFil: Madden, Julie. University of Tennessee; Estados UnidosFil: Alifano Ferrero, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergen, Benjamin. University of California at San Diego; Estados UnidosFil: Bloxsom, Nicholas G.. Ashland University; Estados UnidosFil: Bub, Daniel N.. University of Victoria; CanadáFil: Cai, Zhenguang G.. The Chinese University; Hong KongFil: Chartier, Christopher R.. Ashland University; Estados UnidosFil: Chatterjee, Anjan. University of Pennsylvania; Estados UnidosFil: Conwell, Erin. North Dakota State University; Estados UnidosFil: Wagner Cook, Susan. University of Iowa; Estados UnidosFil: Davis, Joshua D.. University of California at San Diego; Estados UnidosFil: Evers, Ellen R. K.. University of California at Berkeley; Estados UnidosFil: Girard, Sandrine. University of Carnegie Mellon; Estados UnidosFil: Harter, Derek. Texas A&m University Commerce; Estados UnidosFil: Hartung, Franziska. University of Pennsylvania; Estados UnidosFil: Herrera, Eduar. Universidad ICESI; ColombiaFil: Huettig, Falk. Max Planck Institute for Psycholinguistics; Países BajosFil: Humphries, Stacey. University of Pennsylvania; Estados UnidosFil: Juanchich, Marie. University of Essex; Reino UnidoFil: Kühne, Katharina. Universitat Potsdam; AlemaniaFil: Lu, Shulan. Texas A&m University Commerce; Estados UnidosFil: Lynes, Tom. University of East Anglia; Reino UnidoFil: Masson, Michael E. J.. University of Victoria; CanadáFil: Ostarek, Markus. Max Planck Institute for Psycholinguistics; Países BajosFil: Pessers, Sebastiaan. Katholikie Universiteit Leuven; BélgicaFil: Reglin, Rebecca. Universitat Potsdam; AlemaniaFil: Steegen, Sara. Katholikie Universiteit Leuven; BélgicaFil: Thiessen, Erik D.. University of Carnegie Mellon; Estados UnidosFil: Thomas, Laura E.. North Dakota State University; Estados UnidosFil: Trott, Sean. University of California at San Diego; Estados UnidosFil: Vandekerckhove, Joachim. University of California at Irvine; Estados UnidosFil: Vanpaeme, Wolf. Katholikie Universiteit Leuven; BélgicaFil: Vlachou, Maria. Katholikie Universiteit Leuven; BélgicaFil: Williams, Kristina. Texas A&m University Commerce; Estados UnidosFil: Ziv Crispel, Noam. BehavioralSight; Estados Unido

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The landscape of somatic copy-number alteration across human cancers

available in PMC 2010 August 18.A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P50CA90578)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109038))National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109467)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA085859)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA 098101)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, K08CA122833

Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease.

RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). CONCLUSIONS: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD

Characterizing the cancer genome in lung adenocarcinoma

Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours ( n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in similar to 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 ( NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62944/1/nature06358.pd

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.Core funding for this project was provided by the National Institutes of Health (R01-CA172404, PI: S.J. Ramus; and R01-CA168758, PIs: J.A. Doherty and M.A.Rossing), the Canadian Institutes for Health Research (Proof-of-Principle I program, PIs: D.G.Huntsman and M.S. Anglesio), the United States Department of Defense Ovarian Cancer Research Program (OC110433, PI: D.D. Bowtell). A. Talhouk is funded through a Michael Smith Foundation for Health Research Scholar Award. M.S. Anglesio is funded through a Michael Smith Foundation for Health Research Scholar Award and the Janet D. Cottrelle Foundation Scholars program managed by the BC Cancer Foundation. J. George was partially supported by the NIH/National Cancer Institute award number P30CA034196. C. Wang was a Career Enhancement Awardee of the Mayo Clinic SPORE in Ovarian Cancer (P50 CA136393). D.G. Huntsman receives support from the Dr. Chew Wei Memorial Professorship in Gynecologic Oncology, and the Canada Research Chairs program (Research Chair in Molecular and Genomic Pathology). M. Widschwendter receives funding from the European Union’s Horizon 2020 European Research Council Programme, H2020 BRCA-ERC under Grant Agreement No. 742432 as well as the charity, The Eve Appeal (https://eveappeal.org.uk/), and support of the National Institute for Health Research (NIHR) and the University College London Hospitals (UCLH) Biomedical Research Centre. G.E. Konecny is supported by the Miriam and Sheldon Adelson Medical Research Foundation. B.Y. Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. H.R. Harris is 20 supported by the NIH/National Cancer Institute award number K22 CA193860. OVCARE (including the VAN study) receives support through the BC Cancer Foundation and The VGH+UBC Hospital Foundation (authors AT, BG, DGH, and MSA). The AOV study is supported by the Canadian Institutes of Health Research (MOP86727). The Gynaecological Oncology Biobank at Westmead, a member of the Australasian Biospecimen Network-Oncology group, was funded by the National Health and Medical Research Council Enabling Grants ID 310670 & ID 628903 and the Cancer Institute NSW Grants ID 12/RIG/1-17 & 15/RIG/1-16. The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182) and the National Health and Medical Research Council of Australia (NHMRC; ID199600; ID400413 and ID400281). BriTROC-1 was funded by Ovarian Cancer Action (to IAM and JDB, grant number 006) and supported by Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274 and A19694) and the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres. Samples from the Mayo Clinic were collected and provided with support of P50 CA136393 (E.L.G., G.L.K, S.H.K, M.E.S.)