Multi-site Collaboration Research Articles

The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project: Understanding older-age bipolar disorder by combining multiple datasets.

There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project. Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability. Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources. The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD.

Physical activity programs for children diagnosed with cancer: an international environmental scan

Physical activity programs for children diagnosed with cancer may enhance health and quality of life. However, it is unknown where and in what capacity such programs are being offered internationally. To identify physical activity programs for children diagnosed with cancer and summarize program characteristics. Five data sources were searched to identify physical activity programs offered to children diagnosed with cancer. Following confirmation of eligibility, correspondents were sent a series of open-ended questions via email. Data were extracted from responses and summarized descriptively and narratively. Of the 140 unique correspondents contacted, 46 programs, in 10 countries, met eligibility criteria. Responses to open-ended follow-up questions were obtained from 36 programs and were subsequently included in the content analysis. Internationally, the majority of programs are being offered to children in Europe, with mixed cancer types, at different stages of the cancer trajectory. There is relatively equal distribution with regard to the setting in which programs are offered (i.e., community, hospital, combination). All correspondents reported that their program is professionally supervised, and most require that children obtain medical clearance prior to participating. There is considerable variability in terms of other key program (e.g., funding) and physical activity characteristics (e.g., frequency). Findings from this environmental scan highlight where and in what capacity physical activity programs are being offered, providing guidance for those seeking to develop/implement physical activity programs themselves. Moreover, results highlight the current state of practice, underscoring the necessity of international networks, multi-site collaborations, and public relations to ensure all children diagnosed with cancer have access to physical activity programs.

A systematic review of research in psychology training clinics: How far have we come?

Psychology training clinics provide evidence-based, cost-effective psychological services to the general public, while at the same time providing a training ground for future psychotherapists. Research in training clinics can advance the clinical literature, train psychotherapists in evidence-based practice and improve outcomes for clients. However, since the last published review of research published in psychology training clinics (Todd, Kurcias, & Gloster, 1994), it is unclear how much the training clinic literature has advanced in the last two decades or if findings can be synthesized across sites. A systematic, quantitative literature review with strict inclusion and exclusion criteria described 257 empirical studies conducted in training clinics since the previous review (1993–2015). Studies were coded and categorized into themes by three independent raters. Studies explored the nature and organization of training clinics, client characteristics, assessment, intervention, staff and clinical training, as well as research and research training. Across themes, it appeared that the literature has broadened extensively, highlighting that researchers have embraced training clinics as a sample source. Although there was a great breadth of topics researched, there remains insufficient depth in the majority of areas, and a need for multisite collaborations with a shared research agenda across training clinics. The review highlighted the extent to which training clinics are valuable research locations, although more research is needed to compare different training clinics and between training clinics versus nontraining clinics.

Project ECHO: A Disruptive Innovation to Expand Palliative Care (SA503)

•Describe the needs within the larger palliative care community, including workforce shortage, that could be addressed with the use of Project ECHO and other innovative practices.•Explain the concept and practice of Project ECHO around the world and its role in disseminating specialty medical knowledge to medically underserved populations.•Discuss the value of interdisciplinary input and multi-site collaboration in palliative care. Project ECHO uses teleconferencing to link specialist medical teams with community medical care providers who are seeking expertise in a specific field. The specialist teams hold regular “teleECHO” sessions, essentially virtual grand rounds, combining teaching, mentoring and patient case presentations. Over the past few years palliative care programs internationally have begun to utilize this method to expand palliative care knowledge and services in communities. As workforce shortages continue, Project ECHO is an innovative way to increase the capacity of providers by offering education, resources and skills. We will conduct a teleECHO session, using ZOOM videoconferencing. The purposes of the session are to explain and model Project ECHO, facilitate a discussion of how it and other innovative programs can be used in palliative care, to encourage group input and to model interdisciplinary and international collaboration. People can participate in several different ways-through attending the session in person or by logging into the session from anywhere. The interdisciplinary specialist team will facilitate the discussion from the concurrent session room. We will follow a typical ECHOsession agenda:1.Didactic presentation: The didactic topic will be “Project ECHO-A Revolutionary Model for Expanding Access to Care”. The presenter will be a Project ECHO leader/expert. The goal is to familiarize audience/participants with the ECHO model.2.Case presentation and discussion: The “case” will involve a palliative care provider presenting to the session participants some obstacles their organization and providers face. Main question for interdisciplinary specialist team and session participants will be "what innovative solutions have other groups used to address needs/deficiencies in their palliative practice communities?" We will have some of our international ECHO colleagues participating. We will encourage audience to share their own innovative ideas. Interdisciplinary expert panel will share with the audience how Project ECHO has been used to address needs in the PC community.

56 - INITIAL RESULTS FROM THE META-ANALYSIS OF THE WHOLE-EXOMES OF OVER 20,000 SCHIZOPHRENIA CASES AND 45,000 CONTROLS

Background Schizophrenia is a debilitating psychiatric disorder that affects nearly 1% of the population. Schizophrenia has been demonstrated to have a substantial genetic component, with common and rare variants contributing to individual risk. While Genome-Wide Association Studies have implicated over a 140 common risk loci for schizophrenia, rare variant analyses from sequencing studies have had limited success in implicating individual genes, presumably owing to power limitations. Methods Here, we present the Schizophrenia Exome Meta-Analysis (SCHEMA) Consortium, a large multi-site collaboration to aggregate, generate, and analyze high-throughput sequencing data of schizophrenia to advance gene discovery. To date, we have sequenced and processed the whole exomes of over 20,000 schizophrenia cases and 45,000 matched controls using a standardized variant calling and QC pipeline based on GATK and Hail, yielding one of the largest sequencing data sets of a complex trait to date. Our study actively recruited from diverse global populations, and includes individuals of European, Latin American, East Asian, Ashkenazi Jewish, and African American ancestry. Because our exomes were sequenced with various capture technologies over seven years, we developed a novel pipeline to estimate exon-by-exon coverage of all sequencing batches in our data set, and incorporated this information in quality control and analysis. After adjusting for local differences in coverage, we observed comparable quality metrics between different cohorts and sequencing waves. Results We first replicated findings from earlier sequencing studies of schizophrenia, including a substantial enrichment of ultra-rare damaging variants in genes with a near-completion depletion of protein-truncating variants. We also recapitulated a significant burden of disruptive variants in genes and gene sets previously associated with other neurodevelopmental disorders. We present the first gene-based burden results from our exome meta-analysis, and extend the sample using an independent set of 4,000 whole-genome sequenced cases and 7,000 matched controls. Finally, we present a new exome association results browser that allows for easy viewing of identified variants and gene-based results. Discussion In summary, we introduce the largest multi-center effort to aggregate sequencing data of a psychiatric trait, and the initial results from the harmonization and analysis of over 65,000 exomes.

Practical tools and strategies for researchers to increase replicability.

A growing body of evidence indicates that the effects reported in many scientific fields may be overestimated or even false. This problem has gained a lot of attention in the field of psychology, where researchers have even started to speak of a 'replication crisis'. Fortunately, a number of measures to rectify this problem have already been proposed and implemented, some inspired by practices in other scientific fields. In this review, I briefly examine this issue in the field of psychology and suggest some practical tools and strategies that researchers can implement to increase replicability and the overall quality of their scientific research. WHAT THIS PAPER ADDS: Researchers can implement many practical tools and strategies to improve replicability of their findings. Strategies include improving statistical inference, pre-registration, multisite collaboration, and sharing data. Different scientific fields could benefit from looking at each other's best practices.

Toward A database of intracranial electrophysiology during natural language presentation

ABSTRACT Intracranial electrophysiology (iEEG) studies using cognitive tasks contribute to the understanding of the neural basis of language. However, though iEEG is recorded continuously during clinical treatment, due to patient considerations task time is limited. To increase the usefulness of iEEG recordings for language study we provided patients with a tablet pre-loaded with media filled with natural language, wirelessly synchronised to clinical iEEG. This iEEG data collected and time-locked to natural language presentation is particularly applicable for studying the neural basis of combining words into larger contexts. We validate this approach with pilot analyses involving words heard during a movie, tagging syntactic properties and verb contextual probabilities. Event-related averages of high-frequency power (70–170 Hz) identified bilateral perisylvian electrodes with differential responses to syntactic class and a linear regression identified activity associated with contextual probabilities, demonstrating the usefulness of aligning media to iEEG. We imagine future multi-site collaborations building an “intracranial neurolinguistic corpus”.

A Toolbox to Make Multisite Simulation Research Successful

BackgroundThis paper reviews practical strategies for implementing technology and provides recommendations for onsite logistics in a multi-site simulation research collaboration. A small body of literature supports multi-site simulation research and provides direction for research organization, data collection, and communication. There is a gap in the literature relating to multi-site, multiple-patient simulation collaborations, even though multiple patient simulation is a hot topic at professional nursing education meetings. MethodsThe research team conducted a multi-site, multiple patient randomized control trial pilot and full-scale study in 2016 with relatively small funding resources and administrative overhead. ResultsResearchers from two schools of nursing assembled a tool box to guide the planning, implementation, data management, and dissemination phases of research, including practical strategies for success and alternative solutions to overcome challenges encountered. ConclusionThis conceptual paper enables readers to consider how a systematic approach ensures consistency across multiple data collection sites.

Implementing Parental Tobacco Dependence Treatment Within Bronchiolitis QI Collaboratives.

We sought to implement systematic tobacco dependence interventions for parents and/or caregivers as secondary aims within 2 multisite quality improvement (QI) collaboratives for bronchiolitis. We hypothesized that iterative improvements in tobacco dependence intervention strategies would result in improvement in outcomes between collaboratives. This study involved 2 separate yearlong, multisite QI collaboratives that were focused on care provided to inpatients with a primary diagnosis of bronchiolitis. In each collaborative, we provided tools and training in tobacco dependence treatment and expert coaching on interventions for parents as a secondary aim. Data were collected by chart review and results analyzed by using analysis of means and statistical process control analysis. Outcomes between collaboratives were compared by using relative risks. Between both collaboratives, 56 hospitals participated and 6258 inpatient charts were reviewed. In the first collaborative, 22% of identified parents who smoke received tobacco dependence interventions at baseline. This rate increased to 51% during the postintervention period, with special cause revealed by analysis of means. In the second collaborative, 31% of parents who smoke received baseline interventions. This rate increased to 53% by the conclusion of the collaborative, with special cause revealed by statistical process control analysis. The relative risk for providing any cessation intervention in 1 collaborative versus the other was 0.9 (confidence interval 0.8-1.1). Tobacco dependence treatment of parents and/or caregivers can be integrated into bronchiolitis QI by using relatively low-resource strategies. Using a more intensive QI intervention did not alter the rates of screening or intervention for caregivers who smoke.

Precision Risk Analysis of Cancer Therapy with Interactive Nomograms and Survival Plots.

We present the design and evaluation of an integrated problem solving environment for cancer therapy analysis. The environment intertwines a statistical martingale model and a K Nearest Neighbor approach with visual encodings, including novel interactive nomograms, in order to compute and explain a patient's probability of survival as a function of similar patient results. A coordinated views paradigm enables exploration of the multivariate, heterogeneous and few-valued data from a large head and neck cancer repository. A visual scaffolding approach further enables users to build from familiar representations to unfamiliar ones. Evaluation with domain experts show how this visualization approach and set of streamlined workflows enable the systematic and precise analysis of a patient prognosis in the context of cohorts of similar patients. We describe the design lessons learned from this successful, multi-site remote collaboration.

High fidelity hypothermic preservation of primary tissues in organ transplant preservative for single cell transcriptome analysis

BackgroundHigh-fidelity preservation strategies for primary tissues are in great demand in the single cell RNAseq community. A reliable method would greatly expand the scope of feasible multi-site collaborations and maximize the utilization of technical expertise. When choosing a method, standardizability and fidelity are important factors to consider due to the susceptibility of single-cell RNAseq analysis to technical noise. Existing approaches such as cryopreservation and chemical fixation are less than ideal for failing to satisfy either or both of these standards.ResultsHere we propose a new strategy that leverages preservation schemes developed for organ transplantation. We evaluated the strategy by storing intact mouse kidneys in organ transplant preservative solution at hypothermic temperature for up to 4 days (6 h, 1, 2, 3, and 4 days), and comparing the quality of preserved and fresh samples using FACS and single cell RNAseq. We demonstrate that the strategy effectively maintained cell viability, transcriptome integrity, cell population heterogeneity, and transcriptome landscape stability for samples after up to 3 days of preservation. The strategy also facilitated the definition of the diverse spectrum of kidney resident immune cells, to our knowledge the first time at single cell resolution.ConclusionsHypothermic storage of intact primary tissues in organ transplant preservative maintains the quality and stability of the transcriptome of cells for single cell RNAseq analysis. The strategy is readily generalizable to primary specimens from other tissue types for single cell RNAseq analysis.

Research Collaborations Between Women’s Specialist Services, Aboriginal Women and Researchers

When experiencing domestic and family violence (DFV) in Australia, Aboriginal and non-Aboriginal women seek help for diverse needs. In response, women’s specialist DFV services provide a range of programs. Given this diversity and program range, evaluating impact and outcome is challenging. A deeper challenge rests on who decides what to measure and how. This article describes a multi-site research collaboration between women’s specialist services and researchers. Part of the project aimed to identify the perspectives and priorities of Aboriginal women users of three specialist services: one each in an urban, regional and remote location. In a series of iterative steps, Aboriginal women, service workers and researchers explored what was valued in interactions with crisis programs. Each collaboration then moved to identify ways to measures the items, and to determine when and how other service users might be asked to respond. Aboriginal women participated primarily as service users but in overlapping capacities as victims of DFV, as community members, as local researchers and service workers. The underlying principle that guided the research was to respect and acknowledge Aboriginal women as knowledge-holders, producers and translators. However, clear limits to ideas of ‘co-research’ are identified.

Association between attention bias to threat and anxiety symptoms in children and adolescents.

Considerable research links threat-related attention biases to anxiety symptoms in adults, whereas extant findings on threat biases in youth are limited and mixed. Inconsistent findings may arise due to substantial methodological variability and limited sample sizes, emphasizing the need for systematic research on large samples. The aim of this report is to examine the association between threat bias and pediatric anxiety symptoms using standardized measures in a large, international, multi-site youth sample. A total of 1,291 children and adolescents from seven research sites worldwide completed standardized attention bias assessment task (dot-probe task) and child anxiety symptoms measure (Screen for Child Anxiety Related Emotional Disorders). Using a dimensional approach to symptomatology, we conducted regression analyses predicting overall, and disorder-specific, anxiety symptoms severity, based on threat bias scores. Threat bias correlated positively with overall anxiety symptoms severity (ß=0.078, P=.004). Furthermore, threat bias was positively associated specifically with social anxiety (ß=0.072, P=.008) and school phobia (ß=0.076, P=.006) symptoms severity, but not with panic, generalized anxiety, or separation anxiety symptoms. These associations were not moderated by age or gender. These findings indicate associations between threat bias and pediatric anxiety symptoms, and suggest that vigilance to external threats manifests more prominently in symptoms of social anxiety and school phobia, regardless of age and gender. These findings point to the role of attention bias to threat in anxiety, with implications for translational clinical research. The significance of applying standardized methods in multi-site collaborations for overcoming challenges inherent to clinical research is discussed.

Trans‐oceanic remote power hardware‐in‐the‐loop: multi‐site hardware, integrated controller, and electric network co‐simulation

Electric system operators are increasingly concerned with the potential system-wide impacts of the large-scale integration of distributed energy resources including voltage control, protection coordination, and equipment wear. This prompts a need for new simulation techniques that can simultaneously capture all the components of these large integrated smart grid systems. This study describes a novel platform that combines three emerging research areas: power systems co-simulation, power hardware in the loop (PHIL) simulation, and lab–lab links. The platform is distributed, real-time capable, allows for easy internet-based connection from geographically-dispersed participants, and is software platform agnostic. The authors demonstrate its utility by studying real-time PHIL co-simulation of coordinated solar photovoltaic (PV) firming control of two inverters connected in multiple electric distribution network models, prototypical of US and Australian systems. The novel trans-pacific closed-loop system simulation was conducted in real time using a power network simulator and physical PV/battery inverter at power at the National Renewable Energy Laboratory in Golden, CO, USA and a physical PV inverter at power at the Commonwealth Scientific and Industrial Research Organisation's Energy Centre in Newcastle, NSW, Australia. This capability enables smart grid researchers throughout the world to leverage their unique simulation capabilities for multi-site collaborations that can effectively simulate and validate emerging smart grid technology solutions.

GLOBAL INITIATIVES AND FUTURE CHALLENGES

Advances in Alzheimer's disease (AD) have been accelerated through the establishment of large consortia with systematic and longitudinal study and large industry-based research and clinical trials. Programs such as the Alzheimer's Neuroimaging Initiative and Alzheimer's Disease Cooperative Study have advanced our understanding of AD and treatment interventions. However, until recently, such large-scale programs have been essential non-existent for dementia with Lewy bodies (DLB). Large and longitudinal subject sample research is a critical need to advance our capacity to understand and treat this common form of dementia. We reviewed databases including clinicaltrials.gov and NIH Reporter and surveyed DLB investigators in academia and industry to update current research programs in DLB. We found a number of recent efforts to expand basic and clinical research in DLB. This included the funding of a planning grant for a European-based DLB consortium, which has led to several multi-site collaborations. In 2016 the National Institute of Health (NIH) funded the establishment of a nine-site US-based DLB consortium and funded several DLB-focused biomarker studies. In addition, there is increasing evidence of industry-based clinical trials and interest in the development of diagnostic tools with a focus on DLB. It is encouraging to observe an increase in DLB-focused research over the last few years and a willingness of agencies and industry to fund these efforts. Future challenges include improving diagnostic markers for DLB, promoting collaboration, encouraging additional treatment trials, and maintaining the new funding levels for the study and treatment of DLB.

Introducing reform through prescribed policy discourse(s): a critique of policy rhetoric in Maltese education

A central issue in system improvement is the propagation of a common sense of purpose where individual institutions can simultaneously bond with the wider system while exercising autonomy in context – hence the centrality of networks and collaboration (Hopkins 2007). The Maltese state education system responded to this concomitant move towards ‘network governance’ through the introduction of school networks (legally termed ‘colleges’), mandated by the policy document For All Children to Succeed (Ministry of Education, Youth and Employment 2005). I explore the implications of this move for the policy actors involved and the system within which this policy reception, translation and enactment unfold through a documentary analysis of the policy document FACTS, thus depicting how a relatively small state education system utilized multi-site school collaboratives to implement system-wide reform. Despite FACTS’ promise of autonomy, the state’s struggle for the retention of hegemony emerges very strongly – this has implications for policy and practice.

Visualizing Changes in Neuronal Dendritic Morphology in Response to Stress and Pharmacological Challenge.

This unit outlines a protocol for Golgi staining, which has been used extensively to reliably and quantitatively assess alterations in dendritic arborization and spine density as a result of a variety of factors, including chronic administration of glucocorticoids, chronic stress, and pharmacological manipulations. The method stains neurons in their entirety, allowing for sophisticated analyses of branch lengths and numbers as well as patterns of dendritic branching. Advantages of the technique include its usefulness in multisite collaborations and its utility in visualizing neurons in multiple regions within the same brain. Given that it typically labels approximately one in one hundred neurons, many neurons per region of interest can be sampled per animal, greatly increasing the ability to obtain a representative sample of neurons. Limitations include its time-consuming nature, the hazardous chemicals employed, and the inability to use the stain to identify discrete subpopulations of neurons based on their projections, activation, or protein expression. © 2017 by John Wiley & Sons, Inc.

Distribution dilemmas

In this paper, I explore the relationship of democracy to educational leadership; more specifically, to the notion of distributed leadership as it unfolds within policy-mandated multi-site school collaboratives, with particular reference to practices in Malta. Under the policy framework ‘For All Children To Succeed’ introduced in Malta in 2005, Maltese primary and secondary state schools embarked on the process of being organized into networks, legally termed ‘colleges’. I explore leadership distribution among the leaders constituting the college and the subsequent inherent tensions within this educational scenario. The notion of distributed leadership as perceived by the leaders is examined, and especially the leaders’ reception of its presentation in the policy document as the leadership discourse; and its eventual (non-)enactment at both school and college level. A Foucauldian theoretical framework, specifically Foucault’s concepts of power relations, governmentality, discourse, and subjectification, is used to carry out a case study of a Maltese college, collecting data via semi-structured, in-depth interviews, participant observation and documentary analysis. Narrative is both the phenomenon under study and the method of analysis. The policy discourse does not unfold in a participatory democratic manner in practice, resulting in an organizational paradox where leadership enactment in a Maltese college is ‘directed’ from above, rather than ‘distributed’. These findings may be significant for educational practice, policy and theory in terms of the generation of problematization which may lead to further research on this contested topic.

Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts

Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12–40) and Tel Aviv (TLV; n=59, aged 12–36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations.

The Use and Effectiveness of Bundles for Prevention of Central Line-Associated Bloodstream Infections in Neonates: A Review of the Literature.

Central line-associated bloodstream infections (CLABSIs) are an important cause of increased morbidity, mortality, and costs in neonatal intensive care unit (NICU) patients. In recent years, central line bundles have been developed and implemented as a means to reduce infection rates in intensive care units. The objective of this review was to describe central line bundles that are utilized in the neonatal population and evaluate the current evidence on the effectiveness of bundles for prevention of CLABSIs in the NICU. This review shows that care bundles have been successfully used in NICUs (as part of both single-site quality improvement initiatives and large multisite collaboratives) to decrease CLABSI rates. The individual components that comprise the bundle between individual studies varied, but all studies showed a significant reduction in CLABSI rates. The pre- and postintervention design employed by these studies does not allow for conclusions to be drawn as to what specific bundle components are most effective in reducing rates. Further research is needed both to examine the effectiveness of specific components or combinations of components in the bundle and to examine factors that are associated with implementation and adherence to bundles.