Photometric IGM tomography with Subaru/HSC: the large-scale structure of Lyα emitters and IGM transmission in the COSMOS field at z ∼ 5

We present a novel technique called “photometric IGM tomography” to map the intergalactic medium (IGM) at z ≃ 4.9 in the COSMOS field. It utilizes deep narrow-band (NB) imaging to photometrically detect faint Lyα forest transmission in background galaxies across the Subaru/Hyper-Suprime Cam (HSC)’s 1.8sq.deg field of view and locate Lyα emitters (LAEs) in the same cosmic volume. Using ultra-deep HSC images and Bayesian spectral energy distribution fitting, we measure the Lyα forest transmission at z ≃ 4.9 along a large number (140) of background galaxies selected from the DEIMOS10k spectroscopic catalogue at 4.98 < z < 5.89 and the SILVERRUSH LAEs at z ≃ 5.7. We photometrically measure the mean Lyα forest transmission and achieve a result consistent with previous measurements based on quasar spectra. We also measure the angular LAE-Lyα forest cross-correlation and Lyα forest auto-correlation functions and place an observational constraint on the large-scale fluctuations of the IGM around LAEs at z ≃ 4.9. Finally, we present the reconstructed 2D tomographic map of the IGM, co-spatial with the large-scale structure of LAEs, at a transverse resolution of 11h−1cMpc across 140h−1cMpc in the COSMOS field at z ≃ 4.9. We discuss the observational requirements and the potential applications of this new technique for understanding the sources of reionization, quasar radiative history, and galaxy-IGM correlations across z ∼ 3 − 6. Our results represent the first proof-of-concept of photometric IGM tomography, offering a new route to examining early galaxy evolution in the context of the large-scale cosmic web from the epoch of reionization to cosmic noon

Nonequilibrium clumped isotope signals in microbial methane

Methane is a key component in the global carbon cycle with a wide range of anthropogenic and natural sources. Although isotopic compositions of methane have traditionally aided source identification, the abundance of its multiply-substituted “clumped” isotopologues, e.g., 13CH3D, has recently emerged as a proxy for determining methane-formation temperatures; however, the impact of biological processes on methane’s clumped isotopologue signature is poorly constrained. We show that methanogenesis proceeding at relatively high rates in cattle, surface environments, and laboratory cultures exerts kinetic control on 13CH3D abundances and results in anomalously elevated formation temperature estimates. We demonstrate quantitatively that H2 availability accounts for this effect. Clumped methane thermometry can therefore provide constraints on the generation of methane in diverse settings, including continental serpentinization sites and ancient, deep groundwaters.National Science Foundation (U.S.) (EAR-1250394)National Science Foundation (U.S.) (EAR-1322805)Deep Carbon Observatory (Program)Natural Sciences and Engineering Research Council of CanadaDeutsche Forschungsgemeinschaft (Gottfried Wilhelm Leibniz Program)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship)Neil & Anna Rasmussen FoundationGrayce B. Kerr Fund, Inc. (Fellowship)MIT Energy Initiative (Shell-MITEI Graduate Fellowship)Shell International Exploration and Production B.V. (N. Braunsdorf and D. Smit of Shell PTI/EG grant

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 Hobby–Eberly Telescope Dark Energy Experiment (HETDEX) Survey Design, Reductions, and Detections

We describe the survey design, calibration, commissioning, and emission-line detection algorithms for the Hobby–Eberly Telescope Dark Energy Experiment (HETDEX). The goal of HETDEX is to measure the redshifts of over a million Lyα emitting galaxies between 1.88 < z < 3.52, in a 540 deg2 area encompassing a comoving volume of 10.9 Gpc3. No preselection of targets is involved; instead the HETDEX measurements are accomplished via a spectroscopic survey using a suite of wide-field integral field units distributed over the focal plane of the telescope. This survey measures the Hubble expansion parameter and angular diameter distance, with a final expected accuracy of better than 1%. We detail the project’s observational strategy, reduction pipeline, source detection, and catalog generation, and present initial results for science verification in the Cosmological Evolution Survey, Extended Groth Strip, and Great Observatories Origins Deep Survey North fields. We demonstrate that our data reach the required specifications in throughput, astrometric accuracy, flux limit, and object detection, with the end products being a catalog of emission-line sources, their object classifications, and flux-calibrated spectra

Actin Nemaline Myopathy Mouse Reproduces Disease, Suggests Other Actin Disease Phenotypes and Provides Cautionary Note on Muscle Transgene Expression

Mutations in the skeletal muscle α-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G) of ACTA1 (identified in a severe nemaline myopathy patient) fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT) muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ∼30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC) fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations

The Role of Galaxies and AGN in Reionising the IGM - I: Keck Spectroscopy of 5 < z < 7 Galaxies in the QSO Field J1148+5251

We introduce a new method for determining the influence of galaxies and active galactic nuclei (AGN) on the physical state of the intergalactic medium (IGM) at high redshift and illustrate its potential via a first application to the field of the $z=6.42$ QSO J1148+5251. By correlating the spatial positions of spectroscopically-confirmed Lyman break galaxies (LBGs) with fluctuations in the Lyman alpha forest seen in the high signal-to-noise spectrum of a background QSO, we provide a statistical measure of the typical escape fraction of Lyman continuum photons close to the end of cosmic reionisation. Here we use Keck DEIMOS spectroscopy to locate 7 colour-selected LBGs in the redshift range $5.3\lesssim z\lesssim 6.4$ and confirm a faint $z=5.701$ AGN. We then examine the spatial correlation between this sample and Ly$\alpha$/Ly$\beta$ transmission fluctuations in a Keck ESI spectrum of the QSO. Interpreting the statistical HI proximity effect as arising from faint galaxies clustered around the detected LBGs, we translate the observed mean Ly$\alpha$ transmitted flux around an average detected LBG into a constraint on the mean escape fraction $\langle f_{\rm esc}\rangle\geq0.08$ at $z\simeq6$. We also report evidence of the individual transverse HI proximity effect of a $z=6.177$ luminous LBG via a Ly$\beta$ transmission spike and two broad Ly$\alpha$ transmission spikes around the $z=5.701$ AGN. We discuss the possible origin of such associations which suggest that while faint galaxies are primarily driving reionisation, luminous galaxies and AGN may provide important contributions to the UV background or thermal fluctuations of the IGM at $z\simeq6$. Although a limited sample, our results demonstrate the potential of making progress using this method in resolving one of the most challenging aspects of the contribution of galaxies and AGN to cosmic reionisation.Comment: 21 pages, 16 figures, the version accepted in MNRA

Gap-filling eddy covariance methane fluxes : Comparison of machine learning model predictions and uncertainties at FLUXNET-CH4 wetlands

Time series of wetland methane fluxes measured by eddy covariance require gap-filling to estimate daily, seasonal, and annual emissions. Gap-filling methane fluxes is challenging because of high variability and complex responses to multiple drivers. To date, there is no widely established gap-filling standard for wetland methane fluxes, with regards both to the best model algorithms and predictors. This study synthesizes results of different gap-filling methods systematically applied at 17 wetland sites spanning boreal to tropical regions and including all major wetland classes and two rice paddies. Procedures are proposed for: 1) creating realistic artificial gap scenarios, 2) training and evaluating gap-filling models without overstating performance, and 3) predicting halfhourly methane fluxes and annual emissions with realistic uncertainty estimates. Performance is compared between a conventional method (marginal distribution sampling) and four machine learning algorithms. The conventional method achieved similar median performance as the machine learning models but was worse than the best machine learning models and relatively insensitive to predictor choices. Of the machine learning models, decision tree algorithms performed the best in cross-validation experiments, even with a baseline predictor set, and artificial neural networks showed comparable performance when using all predictors. Soil temperature was frequently the most important predictor whilst water table depth was important at sites with substantial water table fluctuations, highlighting the value of data on wetland soil conditions. Raw gap-filling uncertainties from the machine learning models were underestimated and we propose a method to calibrate uncertainties to observations. The python code for model development, evaluation, and uncertainty estimation is publicly available. This study outlines a modular and robust machine learning workflow and makes recommendations for, and evaluates an improved baseline of, methane gap-filling models that can be implemented in multi-site syntheses or standardized products from regional and global flux networks (e.g., FLUXNET).Peer reviewe

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe