The transmembrane protein LRIG2 increases tumor progression in skin carcinogenesis

Over the last few decades, the number of cases of non‐melanoma skin cancer (NMSC) has risen to over 3 million cases every year worldwide. Members of the ERBB receptor family are important regulators of skin development and homeostasis and, when dysregulated, contribute to skin pathogenesis. In this study, we investigated leucine‐rich repeats and immunoglobulin‐like domains 2 (LRIG2), a transmembrane protein involved in feedback loop regulation of the ERBB receptor family during NMSC. LRIG2 was identified to be up‐regulated in various types of squamous cell carcinoma (SCC), but little is known about LRIG2 in cutaneous SCC (cSCC). To investigate the function of LRIG2 in cSCC in vivo, we generated a skin‐specific LRIG2 overexpressing transgenic mouse line (LRIG2‐TG) using the Tet‐Off system. We employed the 7,12‐dimethylbenz(a)anthracene/12‐O‐tetra‐decanoylphorbol‐13‐acetate (DMBA/TPA) two‐stage chemical carcinogenesis model and analyzed the skin during homeostasis and tumorigenesis. LRIG2‐TG mice did not exhibit alterations in skin development or homeostasis but showed an interaction between LRIG2 and thrombospondin‐1, which is often involved in angiogenesis and tumorigenesis. However, during carcinogenesis, transgenic animals showed significantly increased tumor progression and a more rapid development of cSCC. This was accompanied by changes in the ERBB system. After a single TPA application, inflammation of the epidermis was enhanced during LRIG2 overexpression. In human skin samples, LRIG2 expression was identified in the basal layer of the epidermis and in hair follicles of normal skin, but also in cSCC samples. In conclusion, epidermal LRIG2 excess is associated with activated EGFR/ERBB4‐MAPK signaling and accelerated tumor progression in experimentally induced NMSC, suggesting LRIG2 as a potential oncoprotein in skin

Risk governance in organizations

Dieses Buch dokumentiert 10 Jahre Risk-Governance-Forschung an der Universität Siegen. In 50 Beiträgen reflektieren Forscher und Praktiker Risk Governance vor dem Hintergrund ihrer eigenen Forschungen und/oder Erfahrungen und geben jeweils einen Entwicklungsimpuls für die Zukunft der Risk Governance. Das Buch zeigt die große Bandbreite und Tiefe des Forschungsgebietes auf und diskutiert Grundannahmen, Implementierungsfragen, die Rolle der Risk Governance als Transformationsmotor, ihre Wirkung in den verschiedenen betrieblichen Funktionen, Entwicklungsperspektiven und den Beitrag der Risk Governance zu einer nachhaltigen Ausrichtung von Unternehmen.This book documents 10 years of risk governance research at the University of Siegen. In 50 contributions, researchers and practitioners reflect on risk governance against the background of their own research and/or experience and provide a development impetus for the future of risk governance. The book shows the wide range and depth of the research field and discusses basic assumptions, implementation issues, the role of risk governance as transformation engine, its impact in the various operational functions, development perspectives, and the contribution of risk governance to a sustainable orientation of companies

Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia.

Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Platelet number and volume are independent risk factors for heart attack and stroke. Here, we have identified 2 unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterized by low platelet count. N-Ethyl-N-nitrosourea-induced (ENU-induced) missense mutations in Tpm4 or targeted inactivation of the Tpm4 locus led to gene dosage-dependent macrothrombocytopenia in mice. All other blood cell counts in Tpm4-deficient mice were normal. Insufficient TPM4 expression in human and mouse megakaryocytes resulted in a defect in the terminal stages of platelet production and had a mild effect on platelet function. Together, our findings demonstrate a nonredundant role for TPM4 in platelet biogenesis in humans and mice and reveal that truncating variants in TPM4 cause a previously undescribed dominant Mendelian platelet disorder.The research participants were enrolled in the Biomedical Research Centres/Units Inherited Diseases Genetic Evaluation (BRIDGE) Bleeding and Platelet Disorders (BPD) study (UK REC10/H0304/66). We are grateful to all the donors who allowed us to use their samples for this study. We thank Sofia Papadia from the NIHR BioResource for organizing the recalls of BRIDGE-BPD participants. The genome sequencing of the BRIDGE-BPD participants was supported by the NIHR BioResource–Rare Diseases (to ET, KD, and WHO). The NIHR BioResource–Rare Diseases is responsible for the delivery of the rare diseases pilot phase of the 100,000 Genomes Project and is funded by the National Institute for Health Research (NIHR; http://www.nihr.ac.uk). Research in the Ouwehand laboratory also receives funding support from the European Commission, NIHR, Wellcome Trust, Medical Research Council (MRC), and British Heart Foundation under numbers RP-PG-0310-1002 and RG/09/12/28096. SKW is supported by an MRC Clinical Training Fellowship (MR/K023489/1). ADM receives support from the Bristol NIHR Biomedical Research Unit for Cardiovascular Disease. This work was supported by a Project Grant (no. 575535), a Program Grant (no. 1016647), a Fellowship (1063008 to BTK and 1058344 to WSA), Project Grants (to PWG and ECH), and an Independent Research Institutes Infrastructure Support Scheme Grant (no. 361646) from the Australian National Health and Medical Research Council; a fellowship from the Sylvia and Charles Viertel Foundation (to BTK); a start-up grant, a fellowship, and a grant from the German Research Foundation (SFB 688, PL707/1-1 and PL707/2-1 to IP); the Kids’ Cancer Project (to PWG); a Fellowship from the European Hematology Association (to MRT) and the British Heart Foundation (PG/13/77/30375 to MRT); NHS Blood and Transplant (to WHO and MRT); the Australian Cancer Research Fund; and a Victorian State Government Operational Infrastructure Support Grant

Proceedings of the 8th Annual Conference on the Science of Dissemination and Implementation

A1 Introduction to the 8(th) Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers, Lisa Simpson D1 Discussion forum: Population health D&I research Felicia Hill-Briggs D2 Discussion forum: Global health D&I research Gila Neta, Cynthia Vinson D3 Discussion forum: Precision medicine and D&I research David Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, Danielle Adams, David Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians' experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, Dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya VanDeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Leveraging an existing resource for technical assistance: Community-based supervisors in public mental health Shannon Dorsey, Michael Pullmann S9 SBIRT implementation for adolescents in urban federally qualified health centers: Implementation outcomes Shannon Mitchell, Robert Schwartz, Arethusa Kirk, Kristi Dusek, Marla Oros, Colleen Hosler, Jan Gryczynski, Carolina Barbosa, Laura Dunlap, David Lounsbury, Kevin O'Grady, Barry Brown S10 PANEL: Tailoring Implementation Strategies to Context - Expert recommendations for tailoring strategies to context Laura Damschroder, Thomas Waltz, Byron Powell S11 PANEL: Tailoring Implementation Strategies to Context - Extreme facilitation: Helping challenged healthcare settings implement complex programs Mona Ritchie S12 PANEL: Tailoring Implementation Strategies to Context - Using menu-based choice tasks to obtain expert recommendations for implementing three high-priority practices in the VA Thomas Waltz S13 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Siri, rate my therapist: Using technology to automate fidelity ratings of motivational interviewing David Atkins, Zac E. Imel, Bo Xiao, Doğan Can, Panayiotis Georgiou, Shrikanth Narayanan S14 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Identifying indicators of implementation quality for computer-based ratings Cady Berkel, Carlos Gallo, Irwin Sandler, C. Hendricks Brown, Sharlene Wolchik, Anne Marie Mauricio S15 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Improving implementation of behavioral interventions by monitoring emotion in spoken speech Carlos Gallo, C. Hendricks Brown, Sanjay Mehrotra S16 Scorecards and dashboards to assure data quality of health management information system (HMIS) using R Dharmendra Chandurkar, Siddhartha Bora, Arup Das, Anand Tripathi, Niranjan Saggurti, Anita Raj S17 A big data approach for discovering and implementing patient safety insights Eric Hughes, Brian Jacobs, Eric Kirkendall S18 Improving the efficacy of a depression registry for use in a collaborative care model Danielle Loeb, Katy Trinkley, Michael Yang, Andrew Sprowell, Donald Nease S19 Measurement feedback systems as a strategy to support implementation of measurement-based care in behavioral health Aaron Lyon, Cara Lewis, Meredith Boyd, Abigail Melvin, Semret Nicodimos, Freda Liu, Nathanial Jungbluth S20 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Common loop assay: Methods of supporting learning collaboratives Allen Flynn S21 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Innovating audit and feedback using message tailoring models for learning health systems Zach Landis-Lewis S22 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Implementation science and learning health systems: Connecting the dots Anne Sales S23 Facilitation activities of Critical Access Hospitals during TeamSTEPPS implementation Jure Baloh, Marcia Ward, Xi Zhu S24 Organizational and social context of federally qualified health centers and variation in maternal depression outcomes Ian Bennett, Jurgen Unutzer, Johnny Mao, Enola Proctor, Mindy Vredevoogd, Ya-Fen Chan, Nathaniel Williams, Phillip Green S25 Decision support to enhance treatment of hospitalized smokers: A randomized trial Steven Bernstein, June-Marie Rosner, Michelle DeWitt, Jeanette Tetrault, James Dziura, Allen Hsiao, Scott Sussman, Patrick O’Connor, Benjamin Toll S26 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A patient-centered approach to successful community transition after catastrophic injury Michael Jones, Julie Gassaway S27 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - Conducting PCOR to integrate mental health and cancer screening services in primary care Jonathan Tobin S28 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A comparative effectiveness trial of optimal patient-centered care for US trauma care systems Douglas Zatzick S29 Preferences for in-person communication among patients in a multi-center randomized study of in-person versus telephone communication of genetic test results for cancer susceptibility Angela R Bradbury, Linda Patrick-Miller, Brian Egleston, Olufunmilayo I Olopade, Michael J Hall, Mary B Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Amanda Brandt, Dana Farengo-Clark, Andrea Forman, Rikki S Gaber, Cassandra Gulden, Janice Horte, Jessica Long, Rachelle Lorenz Chambers, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill Stopfer, Shirley Yao and Susan Domchek S30 Working towards de-implementation: A mixed methods study in breast cancer surveillance care Erin Hahn, Corrine Munoz-Plaza, Jianjin Wang, Jazmine Garcia Delgadillo, Brian Mittman Michael Gould S31Integrating evidence-based practices for increasing cancer screenings in safety-net primary care systems: A multiple case study using the consolidated framework for implementation research Shuting (Lily) Liang, Michelle C. Kegler, Megan Cotter, Emily Phillips, April Hermstad, Rentonia Morton, Derrick Beasley, Jeremy Martinez, Kara Riehman S32 Observations from implementing an mHealth intervention in an FQHC David Gustafson, Lisa Marsch, Louise Mares, Andrew Quanbeck, Fiona McTavish, Helene McDowell, Randall Brown, Chantelle Thomas, Joseph Glass, Joseph Isham, Dhavan Shah S33 A multicomponent intervention to improve primary care provider adherence to chronic opioid therapy guidelines and reduce opioid misuse: A cluster randomized controlled trial protocol Jane Liebschutz, Karen Lasser S34 Implementing collaborative care for substance use disorders in primary care: Preliminary findings from the summit study Katherine Watkins, Allison Ober, Sarah Hunter, Karen Lamp, Brett Ewing S35 Sustaining a task-shifting strategy for blood pressure control in Ghana: A stakeholder analysis Juliet Iwelunmor, Joyce Gyamfi, Sarah Blackstone, Nana Kofi Quakyi, Jacob Plange-Rhule, Gbenga Ogedegbe S36 Contextual adaptation of the consolidated framework for implementation research (CFIR) in a tobacco cessation study in Vietnam Pritika Kumar, Nancy Van Devanter, Nam Nguyen, Linh Nguyen, Trang Nguyen, Nguyet Phuong, Donna Shelley S37 Evidence check: A knowledge brokering approach to systematic reviews for policy Sian Rudge S38 Using Evidence Synthesis to Strengthen Complex Health Systems in Low- and Middle-Income Countries Etienne Langlois S39 Does it matter: timeliness or accuracy of results? The choice of rapid reviews or systematic reviews to inform decision-making Andrea Tricco S40 Evaluation of the veterans choice program using lean six sigma at a VA medical center to identify benefits and overcome obstacles Sherry Ball, Anne Lambert-Kerzner, Christine Sulc, Carol Simmons, Jeneen Shell-Boyd, Taryn Oestreich, Ashley O'Connor, Emily Neely, Marina McCreight, Amy Labebue, Doreen DiFiore, Diana Brostow, P. Michael Ho, David Aron S41 The influence of local context on multi-stakeholder alliance quality improvement activities: A multiple case study Jillian Harvey, Megan McHugh, Dennis Scanlon S42 Increasing physical activity in early care and education: Sustainability via active garden education (SAGE) Rebecca Lee, Erica Soltero, Nathan Parker, Lorna McNeill, Tracey Ledoux S43 Marking a decade of policy implementation: The successes and continuing challenges of a provincial school food and nutrition policy in Canada Jessie-Lee McIsaac, Kate MacLeod, Nicole Ata, Sherry Jarvis, Sara Kirk S44 Use of research evidence among state legislators who prioritize mental health and substance abuse issues Jonathan Purtle, Elizabeth Dodson, Ross Brownson S45 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 1 designs Brian Mittman, Geoffrey Curran S46 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 2 designs Geoffrey Curran S47 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 3 designs Jeffrey Pyne S48 Linking team level implementation leadership and implementation climate to individual level attitudes, behaviors, and implementation outcomes Gregory Aarons, Mark Ehrhart, Elisa Torres S49 Pinpointing the specific elements of local context that matter most to implementation outcomes: Findings from qualitative comparative analysis in the RE-inspire study of VA acute stroke care Edward Miech S50 The GO score: A new context-sensitive instrument to measure group organization level for providing and improving care Edward Miech S51 A research network approach for boosting implementation and improvement Kathleen Stevens, I.S.R.N. Steering Council S52 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - The value of qualitative methods in implementation research Alison Hamilton S53 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Learning evaluation: The role of qualitative methods in dissemination and implementation research Deborah Cohen S54 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Qualitative methods in D&I research Deborah Padgett S55 PANEL: Maps & models: The promise of network science for clinical D&I - Hospital network of sharing patients with acute and chronic diseases in California Alexandra Morshed S56 PANEL: Maps & models: The promise of network science for clinical D&I - The use of social network analysis to identify dissemination targets and enhance D&I research study recruitment for pre-exposure prophylaxis for HIV (PrEP) among men who have sex with men Rupa Patel S57 PANEL: Maps & models: The promise of network science for clinical D&I - Network and organizational factors related to the adoption of patient navigation services among rural breast cancer care providers Beth Prusaczyk S58 A theory of de-implementation based on the theory of healthcare professionals’ behavior and intention (THPBI) and the becker model of unlearning David C. Aron, Divya Gupta, Sherry Ball S59 Observation of registered dietitian nutritionist-patient encounters by dietetic interns highlights low awareness and implementation of evidence-based nutrition practice guidelines Rosa Hand, Jenica Abram, Taylor Wolfram S60 Program sustainability action planning: Building capacity for program sustainability using the program sustainability assessment tool Molly Hastings, Sarah Moreland-Russell S61 A review of D&I study designs in published study protocols Rachel Tabak, Alex Ramsey, Ana Baumann, Emily Kryzer, Katherine Montgomery, Ericka Lewis, Margaret Padek, Byron Powell, Ross Brownson S62 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Model simulation techniques to estimate the cost of implementing foundational public health services Cezar Brian Mamaril, Glen Mays, Keith Branham, Lava Timsina S63 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Inter-organizational network effects on the implementation of public health services Glen Mays, Rachel Hogg S64 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Implementation fidelity, coalition functioning, and community prevention system transformation using communities that care Abigail Fagan, Valerie Shapiro, Eric Brown S65 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Expanding capacity for implementation of communities that care at scale using a web-based, video-assisted training system Kevin Haggerty, David Hawkins S66 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Effects of communities that care on reducing youth behavioral health problems Sabrina Oesterle, David Hawkins, Richard Catalano S68 When interventions end: the dynamics of intervention de-adoption and replacement Virginia McKay, M. Margaret Dolcini, Lee Hoffer S69 Results from next-d: can a disease specific health plan reduce incident diabetes development among a national sample of working-age adults with pre-diabetes? Tannaz Moin, Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk, Charles Chan, Abigail Keckhafer, Robert Luchs, Sam Ho, Carol Mangione S70 Implementing smoking cessation interventions in primary care settings (STOP): using the interactive systems framework Peter Selby, Laurie Zawertailo, Nadia Minian, Dolly Balliunas, Rosa Dragonetti, Sarwar Hussain, Julia Lecce S71 Testing the Getting To Outcomes implementation support intervention in prevention-oriented, community-based settings Matthew Chinman, Joie Acosta, Patricia Ebener, Patrick S Malone, Mary Slaughter S72 Examining the reach of a multi-component farmers’ market implementation approach among low-income consumers in an urban context Darcy Freedman, Susan Flocke, Eunlye Lee, Kristen Matlack, Erika Trapl, Punam Ohri-Vachaspati, Morgan Taggart, Elaine Borawski S73 Increasing implementation of evidence-based health promotion practices at large workplaces: The CEOs Challenge Amanda Parrish, Jeffrey Harris, Marlana Kohn, Kristen Hammerback, Becca McMillan, Peggy Hannon S74 A qualitative assessment of barriers to nutrition promotion and obesity prevention in childcare Taren Swindle, Geoffrey Curran, Leanne Whiteside-Mansell, Wendy Ward S75 Documenting institutionalization of a health communication intervention in African American churches Cheryl Holt, Sheri Lou Santos, Erin Tagai, Mary Ann Scheirer, Roxanne Carter, Janice Bowie, Muhiuddin Haider, Jimmie Slade, Min Qi Wang S76 Reduction in hospital utilization by underserved patients through use of a community-medical home Andrew Masica, Gerald Ogola, Candice Berryman, Kathleen Richter S77 Sustainability of evidence-based lay health advisor programs in African American communities: A mixed methods investigation of the National Witness Project Rachel Shelton, Lina Jandorf, Deborah Erwin S78 Predicting the long-term uninsured population and analyzing their gaps in physical access to healthcare in South Carolina Khoa Truong S79 Using an evidence-based parenting intervention in churches to prevent behavioral problems among Filipino youth: A randomized pilot study Joyce R. Javier, Dean Coffey, Sheree M. Schrager, Lawrence Palinkas, Jeanne Miranda S80 Sustainability of elementary school-based health centers in three health-disparate southern communities Veda Johnson, Valerie Hutcherson, Ruth Ellis S81 Childhood obesity prevention partnership in Louisville: creative opportunities to engage families in a multifaceted approach to obesity prevention Anna Kharmats, Sandra Marshall-King, Monica LaPradd, Fannie Fonseca-Becker S82 Improvements in cervical cancer prevention found after implementation of evidence-based Latina prevention care management program Deanna Kepka, Julia Bodson, Echo Warner, Brynn Fowler S83 The OneFlorida data trust: Achieving health equity through research & training capacity building Elizabeth Shenkman, William Hogan, Folakami Odedina, Jessica De Leon, Monica Hooper, Olveen Carrasquillo, Renee Reams, Myra Hurt, Steven Smith, Jose Szapocznik, David Nelson, Prabir Mandal S84 Disseminating and sustaining medical-legal partnerships: Shared value and social return on investment James Teufe

Optimierte Aspektausführungs-Mechanismen innerhalb von Virtuellen Maschinen für Eingebettete Systeme

Der rasant wachsende Mobilgerätemarkt verlangt nach immer komplexeren Anwendungen für eingebettete Mobilgeräte, wie Smartphones. Um diese Komplexität beherrschbar zu machen und gleichzeitig die Produktzyklen möglichst kurz zu halten, ist es nötig fortgeschrittene Softwareentwicklungsmethoden anzuwenden. Die aspektorientierte Programmierung (AOP) stellt fortgeschrittene Modularisierungs- und Abstraktionsmechanismen zur Verfügung. Die wichtigsten Vorteile dieses Konzeptes sind die verbesserte Wartbarkeit, Wiederverwendbarkeit und Erweiterbarkeit von Anwendungen. Darüber hinaus ist dynamische Aspektorientierung dazu geeignet die dynamische Anpassung von mobilen Anwendungen an wechselnde Kontexte, wie z.B. den Standort, zu realisieren. Allerdings schränkt der Overhead, der durch die zusätzlichen Abstraktionsmechanismen entsteht, die Anwendbarkeit auf eingebettete Mobilgeräte ein, da diese im Vergleich zu Desktop PCs beschränkte Ressourcen (CPU, Speicher) aufweisen. Um dieses Problem zu bewältigen, präsentieren wir eine Reihe von Optimierungen, welche den Overhead von typischen AOP-Mechanismen signifikant reduzieren und damit AOP für eingebettet Mobilgeräte anwendbar machen. Die Grundlage unserer Arbeit ist eine gründliche Analyse des Overheads, der typischerweise durch die Realisierung von AOP-Mechanismen entsteht. Die Kernidee unseres Ansatzes ist eine tiefe Integration der AOP-Mechanismen in die virtuelle Maschine. Zu diesem Zweck verschieben wir diese Mechanismen, wie etwa die Registrierung von aktiven Aspekten, auf die Ebene der JVM. Weiterhin optimieren wir die Ausführung von AOP Programmen durch die Einführung von Cache-Mechanismen, sowie spezialisierten Bytecode-Instruktionen, die auf die Ausführung von AOP-Mechanismen zugeschnitten sind. Darüber hinaus analysieren wir AOP-spezifische semantische Code-Eigenschaften und entwickeln darauf aufbauend Optimierungen, die sich diese Eigenschaften und typische AOP Benutzungsschemata zunutze machen. Zusätzlich zu den AOP-Optimierungen realisieren wir einen effizienten dynamischen Aspekt-Deploy Mechanismus. Wir wenden unsere Optimierungen auf die Java-basierte aspektorientierte Programmiersprache ObjectTeams an, indem wir die extrem kleine und für eingebettete Systeme portierte JamVM erweitern. Um unseren Ansatz zu evaluieren führen wir Mikro-Benchmarks aus und untersuchen den Effekt unserer Optimierungen auf eine echte Anwendung. Unsere Evaluierung zeigt eine erhebliche Performanz-Steigerung für die Aspekt-Aktivierung und die Aspekt-Ausführung von ObjectTeams. Unsere Optimierungen verbessern die Performanz von häufig verwendeten AOP-Konstrukten um bis zu 90%. Gleichzeitig verringern wir die Code-Größe adaptierter Klassen, was ebenfalls wichtig ist für kleine Geräte. Schließlich zeigen wir mit unserer Fallstudie, der Spieleanwendung OTPong, dass unser Ansatz in der Lage ist, die Ausführungszeit von echten Anwendungen signifikant zu optimieren. Unser wichtigster Beitrag ist die signifikante Reduzierung des Overheads von höheren AOP-Konstrukten, die wir durch unserer Experimente untermauern konnten. Der Erfolg der Optimierungen zeigt, dass fortgeschrittene höhere Abstraktionstechniken wie AOP effizient auf eingebetteten Mobilgeräten verwendet werden können. Außerdem zeigt unserer Arbeit, wie effizientes dynamisches Aspekt-Deployment auf der Ebene der JVM umgesetzt werden kann. Dadurch konnten wir die dynamischen Fähigkeiten von ObjectTeams maßgeblich erweitern.The rapidly growing mobile market has stimulated the demand for more and more complex custom applications for embedded mobile devices, for example, smart phones. To manage this complexity and, at the same time, to keep the time to market small, advanced software engineering methods have to be applied. Aspect-oriented programming (AOP) provides advanced modularization and abstraction mechanisms. The main advantages of this concept are improved maintainability, reusability, and extensibility of applications. Furthermore, dynamic AOP can be used to implement the dynamic adaptation of mobile device applications to changing contexts, like the location. However, the overhead introduced by the additional abstraction mechanisms limits the applicability to embedded mobile devices because they have limited resources (CPU, memory) compared to desktop PCs. To overcome this problem, we present a set of optimizations that significantly reduce the overhead of common AOP mechanisms and, finally, make AOP applicable for embedded mobile devices. The foundation of our work is a thorough analysis of the overhead that is typically generated by the realization of AOP mechanisms. The key idea of our approach is a deep integration of AOP mechanisms into the virtual machine. To this end, we shift mechanisms like the registration of activated aspects to the level of the JVM. Furthermore, we optimize the execution of AOP programs by introducing caching mechanisms and specialized bytecode instructions that are tailored for the execution of AOP mechanisms. Moreover, we analyze AOP-specific semantic code properties in order to develop optimizations that utilize these AOP-specific semantic information and that exploit typical AOP usage schemes. In addition to the AOP optimizations, we realize an efficient dynamic aspect deployment mechanism. We apply our optimizations to the Java-based aspect-oriented programming language ObjectTeams by extending the extremely small and portable JamVM Java virtual machine. To evaluate our approach, we execute micro benchmarks, investigate the effect of our optimizations on a real-world application, and finally discuss the transferability of our optimizations to other approaches. Our evaluation shows a considerable performance gain for the aspect activation and the aspect execution of ObjectTeams. In particular, we demonstrate that our optimizations improve the performance of commonly used AOP mechanisms by up to 90%. At the same time, we reduce the code size of the adapted classes, which is also important for small devices. Finally, with our case study, namely the OTPong game application, we show that our approach is capable of significantly optimizing the execution time of real-word applications. Our main contribution is a significant reduction of the overhead of high-level AOP constructs, which is also demonstrated by the results of our experiments. The success of the optimizations provides evidence that advanced high-level abstraction techniques like AOP can be efficiently used in embedded mobile devices. Furthermore, our work shows that efficient dynamic aspect deployment can be supported on the level of the JVM. This substantially enhances the dynamic capabilities of ObjectTeams

Digitization of the Mary Hamilton papers

Held at The John Rylands Library, Manchester, the Mary Hamilton Papers are a valuable, but still largely untapped resource for linguistic, cultural and literary studies focussing on the late eighteenth century. In her diaries Lady Mary Hamilton (1756-1816) documents daily life and friendships with intellectual figures of the time, for instance Horace Walpole and members of the Bluestocking circle, which included Elizabeth Montagu and Frances Burney. The archive also contains letters written to Lady Mary Hamilton by her family and other members of her social network. The aim of this project is to prepare a digital edition of materials from the Mary Hamilton Papers with TEI-conformant XML mark-up, in which both a facsimile of the manuscripts and their transliterations (preserving the original spelling, punctuation and layout) will be displayed. In addition, the edition will offer rich meta-data and mark-up of places, persons and literary works, as well as normalized spellings, which will assist searches for linguistic features differing from Present-day English such as (non-)capitalisation (e.g. english, Breakfast) and past tense spellings like dress’d and staid. Drawing on material from the Mary Hamilton Papers and the Corpus of Late Modern English Prose, we provide a case study to illustrate the usefulness of the Mary Hamilton Papers for the study of language change and social networks in the Late Modern period

Clinical effectiveness of manual therapy for the management of musculoskeletal and non-musculoskeletal conditions : systematic review and update of UK evidence report

Background: This systematic review updated and extended the "UK evidence report" by Bronfort et al. (Chiropr Osteopath 18:3, 2010) with respect to conditions/interventions that received an 'inconclusive’ or 'negative’ evidence rating or were not covered in the report. Methods: A literature search of more than 10 general medical and specialised databases was conducted in August 2011 and updated in March 2013. Systematic reviews, primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included. Study quality was assessed using standardised instruments, studies were summarised, and the results were compared against the evidence ratings of Bronfort. These were either confirmed, updated, or new categories not assessed by Bronfort were added. Results: 25,539 records were found; 178 new and additional studies were identified, of which 72 were systematic reviews, 96 were randomised controlled trials, and 10 were non-randomised primary studies. Most 'inconclusive’ or 'moderate’ evidence ratings of the UK evidence report were confirmed. Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases (manipulation/mobilisation [with exercise] for rotator cuff disorder; spinal mobilisation for cervicogenic headache; and mobilisation for miscellaneous headache). In addition, evidence was identified on a large number of non-musculoskeletal conditions not previously considered; most of this evidence was rated as inconclusive. Conclusions: Overall, there was limited high quality evidence for the effectiveness of manual therapy. Most reviewed evidence was of low to moderate quality and inconsistent due to substantial methodological and clinical diversity. Areas requiring further research are highlighted