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Sökning: WFRF:(Downey E.)

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1.
  • Jung, A, et al. (författare)
  • Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe
  • 2021
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.MethodsIn this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.ResultsUp to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0–18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7–35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4–17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).ConclusionSARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.
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2.
  • Cunningham, A. L., et al. (författare)
  • Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older
  • 2016
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 375:11, s. 1019-1032
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01(B) adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1: 1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.govnumbers, NCT01165177 and NCT01165229.)
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3.
  • Downey, Harriet, et al. (författare)
  • Training future generations to deliver evidence-based conservation and ecosystem management
  • 2021
  • Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
  • Forskningsöversikt (refereegranskat)abstract
    • 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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4.
  • Van Der Veen, A. M. H., et al. (författare)
  • International comparison CCQM-K112 biogas
  • 2020
  • Ingår i: Metrologia. - : Institute of Physics Publishing. - 0026-1394 .- 1681-7575. ; 57:1 A
  • Tidskriftsartikel (refereegranskat)abstract
    • At the highest metrological level, biogas standards are commonly prepared gravimetrically as PSMs (primary standard mixtures). This international key comparison addresses the composition of biogas, to support calibration and measurement services for this renewable energy gas. The mixtures contain nitrogen, carbon dioxide, methane, ethane, propane, hydrogen and oxygen and represent the composition of biogas from landfills. The results in this Track C key comparison on the composition of biogas are generally good. Some of the datasets, especially that of oxygen, showed substantial extra dispersion, that could not be explained by the stated uncertainties. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA). 
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5.
  • Hall, CL, et al. (författare)
  • Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial
  • 2019
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e027583-
  • Tidskriftsartikel (refereegranskat)abstract
    • Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.Methods and analysisThis parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).Ethics and disseminationThe findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).Trial registration numbersISRCTN70758207andNCT03483493; Pre-results.
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6.
  • Pinseel, E., et al. (författare)
  • Strain-specific transcriptional responses overshadow salinity effects in a marine diatom sampled along the Baltic Sea salinity cline
  • 2022
  • Ingår i: Isme Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370.
  • Tidskriftsartikel (refereegranskat)abstract
    • The salinity gradient separating marine and freshwater environments represents a major ecological divide for microbiota, yet the mechanisms by which marine microbes have adapted to and ultimately diversified in freshwater environments are poorly understood. Here, we take advantage of a natural evolutionary experiment: the colonization of the brackish Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To understand how diatoms respond to low salinity, we characterized transcriptomic responses of acclimated S. marinoi grown in a common garden. Our experiment included eight strains from source populations spanning the Baltic Sea salinity cline. Gene expression analysis revealed that low salinities induced changes in the cellular metabolism of S. marinoi, including upregulation of photosynthesis and storage compound biosynthesis, increased nutrient demand, and a complex response to oxidative stress. However, the strain effect overshadowed the salinity effect, as strains differed significantly in their response, both regarding the strength and the strategy (direction of gene expression) of their response. The high degree of intraspecific variation in gene expression observed here highlights an important but often overlooked source of biological variation associated with how diatoms respond to environmental change.
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7.
  • Amano, Tatsuya, et al. (författare)
  • Transforming Practice : Checklists for Delivering Change
  • 2022
  • Ingår i: Transforming Conservation : A Practical Guide to Evidence and Decision Making - A Practical Guide to Evidence and Decision Making. - 9781800648562 - 9781800648586 ; , s. 367-386
  • Bokkapitel (refereegranskat)abstract
    • Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists is provided.
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9.
  • Defrere, D., et al. (författare)
  • L'-band AGPM vector vortex coronagraph's first light on LBTI/LMIRCam
  • 2014
  • Ingår i: Adaptive Optics Systems IV. - : SPIE. - 9780819496164
  • Konferensbidrag (refereegranskat)abstract
    • We present the first observations obtained with the L'-band AGPM vortex coronagraph recently installed on LBTI/LMIRCam. The AGPM (Annular Groove Phase Mask) is a vector vortex coronagraph made from diamond subwavelength gratings. It is designed to improve the sensitivity and dynamic range of high-resolution imaging at very small inner working angles, down to 0.09 arcseconds in the case of LBTI/LMIRCam in the L' band. During the first hours on sky, we observed the young A5V star HR8799 with the goal to demonstrate the AGPM performance and assess its relevance for the ongoing LBTI planet survey (LEECH). Preliminary analyses of the data reveal the four known planets clearly at high SNR and provide unprecedented sensitivity limits in the inner planetary system (down to the diffraction limit of 0.09 arcseconds).
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10.
  • Downey, Alisen E., et al. (författare)
  • Soil carbon sequestration in urban afforestation sites in New York City
  • 2021
  • Ingår i: Urban Forestry & Urban Greening. - : Elsevier BV. - 1618-8667 .- 1610-8167. ; 65
  • Tidskriftsartikel (refereegranskat)abstract
    • There is great interest in the ability of afforestation programs to sequester carbon, improve soil health, and provide other ecological benefits to urban areas. However, the capacity of urban soils to support successful afforestation and sequester carbon is poorly understood. This study quantified soil carbon in a series of experimental restoration sites established between 2009 and 2011 as part of the MillionTreesNYC Afforestation Project in New York City. Soil cores (0-100 cm) were collected at 10 sites and analyzed for total carbon content. Data were analyzed with respect to depth (0-10, 10-30, 30-70, 70-90, 90-100 cm), high (six species) versus low (two species) diversity planting palettes, and afforestation success (high or low). Results were compared with data from regional reference forest, degraded urban sites in New York City, and disturbed and undisturbed sites in other cities. High success afforestation sites had significantly larger carbon pools than low success afforestation sites and degraded NYC sites. We suggest that these differences were created by interactions between initial site conditions that facilitated plant community establishment and growth, which in turn increased soil carbon accumulation. These initial site conditions include land use history that influences soil physical and chemical factors, as well as proximity to existing forest stands. Diversity treatments had no effect on soil carbon levels, but these may need a longer time period to emerge. These results suggest that afforestation may enhance the capacity of urban soils to store carbon compared to urban degraded soils, but that urban soil properties and site characteristics constrain this capacity.
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11.
  • Garshick, Eric, et al. (författare)
  • Respiratory Health after Military Service in Southwest Asia and Afghanistan An Official American Thoracic Society Workshop Report
  • 2019
  • Ingår i: Proceedings of the American Thoracic Society online. - : American Thoracic Society. - 1546-3222 .- 1943-5665. ; 16:8, s. E1-E16
  • Tidskriftsartikel (refereegranskat)abstract
    • Since 2001, more than 2.7 million U.S. military personnel have been deployed in support of operations in Southwest Asia and Afghanistan. Land-based personnel experienced elevated exposures to particulate matter and other inhalational exposures from multiple sources, including desert dust, burn pit combustion, and other industrial, mobile, or military sources. A workshop conducted at the 2018 American Thoracic Society International Conference had the goals of: 1) identifying key studies assessing postdeployment respiratory health, 2) describing emerging research, and 3) highlighting knowledge gaps. The workshop reviewed epidemiologic studies that demonstrated more frequent encounters for respiratory symptoms postdeployment compared with nondeployers and for airway disease, predominantly asthma, as well as case series describing postdeployment dyspnea, asthma, and a range of other respiratory tract findings. On the basis of particulate matter effects in other populations, it also is possible that deployers experienced reductions in pulmonary function as a result of such exposure. The workshop also gave particular attention to constrictive bronchiolitis, which has been reported in lung biopsies of selected deployers. Workshop participants had heterogeneous views regarding the definition and frequency of constrictive bronchiolitis and other small airway pathologic findings in deployed populations. The workshop concluded that the relationship of airway disease, including constrictive bronchiolitis, to exposures experienced during deployment remains to be better defined. Future clinical and epidemiologic research efforts should address better characterization of deployment exposures; carry out longitudinal assessment of potentially related adverse health conditions, including lung function and other physiologic changes; and use rigorous histologic, exposure, and clinical characterization of patients with respiratory tract abnormalities.
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12.
  • Gilljam, Marita, 1956, et al. (författare)
  • Airway inflammation and infection in congenital bilateral absence of the vas deferens
  • 2004
  • Ingår i: Am J Respir Crit Care Med. ; 169:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In cystic fibrosis (CF), airway disease begins early in life. Bacteria and elevated levels of neutrophils and inflammatory mediators have been detected in bronchoalveolar lavage (BAL) fluid from infants with CF. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are common in men with congenital bilateral absence of the vas deferens (CBAVD) and it has been suggested that this syndrome represents a mild form of CF. We hypothesized that men with CBAVD also have subclinical pulmonary disease. Bronchoscopy with BAL, viral and quantitative bacterial cultures, and analyses of total and differential cell count, cytokines, and free neutrophil elastase was performed in eight men with CBAVD, who had mutations in the CFTR and intermediate or elevated sweat chloride levels, and in four healthy control subjects. There was light growth of Staphylococcus aureus in one of eight men with CBAVD, and small numbers of opportunistic gram-negative bacteria in six of eight men with CBAVD and in one control subject. BAL cell counts and neutrophil elastase were within the normal range. Interleukin-8 and tumor necrosis factor-alpha levels were higher for men with CBAVD than for control subjects. These data suggest that mutations in the CFTR in men with CBAVD, in addition to causing infertility, lead to subclinical bacterial pulmonary infection and inflammation consistent with mild CF.
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13.
  • Mejía, Gisselle A., et al. (författare)
  • Nitrogen cycling and urban afforestation success in New York City
  • 2022
  • Ingår i: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582. ; 32:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Afforestation projects are a growing focus of urban restoration efforts to rehabilitate degraded landscapes and develop new forests. Urban forests provide myriad valuable ecosystem services essential for urban sustainability and resilience. These essential services are supported by natural soil microbial processes that transform organic matter to critical nutrients for plant community establishment and development. Nitrogen (N) is the most limiting nutrient in forest ecosystems, yet little information is known about N cycling in urban afforestation efforts. This study examined microbially mediated processes of carbon (C) and N cycling in 10 experimental afforested sites established across New York City parklands under the MillionTreesNYC initiative. Long-term research plots were established between 2009 and 2011 at each site with low and high diversity (two vs. six tree species) treatments. In 2018, 1-m soil cores were collected from plots at each site and analyzed for microbial biomass and respiration, potential net N mineralization, and nitrification, denitrification potential, soil inorganic N, and total soil N. Field observations revealed markedly different trajectories between sites that exhibited a closed canopy and leaf litter layer derived from trees that were planted and those that did not fit this description. These two metrics served to group sites into two categories (high vs. low) of afforestation success. We hypothesized that: (1) afforestation success would be correlated with rates of C and N cycling, (2) high diversity restoration techniques would affect these processes, and (3) inherent soil properties interact with plants and environmental conditions to affect the development of these processes over time. We found that high success sites had significantly higher rates of C and N cycling processes, but low and high diversity treatments showed no differences. Low success sites were more likely to have disturbed soil profiles with human-derived debris. Afforestation success appears to be driven by interactions between initial site conditions that facilitate plant community establishment and development that in turn enable N accumulation and cycling, creating positive feedbacks for success. 
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14.
  • Ozanne, Julie L., et al. (författare)
  • Assessing the Societal Impact of Research : The Relational Engagement Approach
  • 2017
  • Ingår i: Journal of Public Policy & Marketing JPP&M. - : SAGE Publications. - 0743-9156 .- 1547-7207. ; 36:1, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Marketing and policy researchers aiming to increase the societal impact of their scholarship should engage directly with relevant stakeholders. For maximum societal effect, this engagement needs to occur both within the research process and throughout the complex process of knowledge transfer. The authors propose that a relational engagement approach to research impact complements and builds on traditional approaches. Traditional approaches to impact employ bibliometric measures and focus on the creation and use of journal articles by scholarly audiences, an important but incomplete part of the academic process. The authors recommend expanding the strategies and measures of impact to include process assessments for specific stakeholders across the entire course of impact, from the creation, awareness, and use of knowledge to societal impact. This relational engagement approach involves the cocreation of research with audiences beyond academia. The authors hope to begin a dialogue on the strategies researchers can use to increase the potential societal benefits of their research.
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16.
  • Senadheera, Dilani B, et al. (författare)
  • Regulation of bacteriocin production and cell death by the VicRK signaling system in Streptococcus mutans
  • 2012
  • Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 194:6, s. 1307-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • The VicRK two-component signaling system modulates biofilm formation, genetic competence, and stress tolerance in Streptococcus mutans. We show here that the VicRK modulates bacteriocin production and cell viability, in part by direct modulation of competence-stimulating peptide (CSP) production in S. mutans. Global transcriptome and real-time transcriptional analysis of the VicK-deficient mutant (SmuvicK) revealed significant modulation of several bacteriocin-related loci, including nlmAB, nlmC, and nlmD (P < 0.001), suggesting a role for the VicRK in producing mutacins IV, V, and VI. Bacteriocin overlay assays revealed an altered ability of the vic mutants to kill related species. Since a well-conserved VicR binding site (TGTWAH-N(5)-TGTWAH) was identified within the comC coding region, we confirmed VicR binding to this sequence using DNA footprinting. Overexpression of the vic operon caused growth-phase-dependent repression of comC, comDE, and comX. In the vic mutants, transcription of nlmC/cipB encoding mutacin V, previously linked to CSP-dependent cell lysis, as well as expression of its putative immunity factor encoded by immB, were significantly affected relative to the wild type (P < 0.05). In contrast to previous reports that proposed a hyper-resistant phenotype for the VicK mutant in cell viability, the release of extracellular genomic DNA was significantly enhanced in SmuvicK (P < 0.05), likely as a result of increased autolysis compared with the parent. The drastic influence of VicRK on cell viability was also demonstrated using vic mutant biofilms. Taken together, we have identified a novel regulatory link between the VicRK and ComDE systems to modulate bacteriocin production and cell viability of S. mutans.
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17.
  • Simonds, Erin F., et al. (författare)
  • Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma
  • 2021
  • Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Glioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.Methods We used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.Results ICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.Conclusions Our data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.
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18.
  • Wood, Gavin, et al. (författare)
  • Designing for Digital Playing Out
  • 2019
  • Ingår i: CHI 2019. - New York, NY, USA : ASSOC COMPUTING MACHINERY.
  • Konferensbidrag (refereegranskat)abstract
    • We report on a design-led study in the UK that aimed to understand barriers to children (aged 5 to 14 years) 'playing out' in their neighbourhood and explore the potential of the Internet of Things (IoT) for supporting children's free play that extends outdoors. The study forms a design ethnography, combining observational fieldwork with design prototyping and co-creative activities across four linked workshops, where we used BBC micro:bit devices to co-create new IoT designs with the participating children. Our collective account contributes new insights about the physical and interactive features of micro:bits that shaped play, gameplay, and social interaction in the workshops, illuminating an emerging design space for supporting 'digital playing out' that is grounded in empirical instances. We highlight opportunities for designing for digital playing out in ways that promote social negotiation, supports varying participation, allows for integrating cultural influences, and accounts for the weaving together of placemaking and play.
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