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KEY POINTS: Sarcopenia or skeletal muscle loss is one of the most frequent complications that contributes to mortality and morbidity in patients with chronic obstructive pulmonary disease (COPD). Unlike chronic hypoxia, prolonged intermittent hypoxia is a frequent, underappreciated and clinically relevant model of hypoxia in patients with COPD. We developed a novel, in vitro myotube model of prolonged intermittent hypoxia with molecular and metabolic perturbations, mitochondrial oxidative dysfunction and consequent sarcopenic phenotype. In vivo studies in skeletal muscle from a mouse model of COPD shared responses with our myotube model establishing pathophysiological relevance of our studies. These data lay the foundation for translational studies in human COPD to target prolonged, nocturnal hypoxemia to prevent sarcopenia in these patients. ABSTRACT: Nocturnal hypoxemia that is common in chronic obstructive pulmonary disease (COPD) patients is associated with skeletal muscle loss or sarcopenia, which contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of hypoxia in skeletal muscle occurs through the duration of sleep followed by normoxia during the day in contrast to recurrent brief hypoxic episodes during obstructive sleep apnea (OSA). Adaptive cellular responses to PIH are not known. Responses to PIH induced by 3-cycles of 8h hypoxia followed by 16h normoxia were compared to those during chronic hypoxia (CH) or normoxia for 72h in murine C2C12 and human inducible pluripotent stem cell-derived differentiated myotubes. RNA sequencing followed by downstream analyses were complemented by experimental validation of responses that included both unique and shared perturbations in ribosomal and mitochondrial function during PIH and CH. A sarcopenic phenotype characterized by decreased myotube diameter and protein synthesis, and increased phosphorylation of eIF2α (Ser51) by eIF2α kinase, GCN-2 (general controlled non-derepressed-2), occurred during both PIH and CH. Mitochondrial oxidative dysfunction, disrupted supercomplex assembly, lower activity of Complexes I, III, IV and V, and reduced intermediary metabolite concentrations occurred during PIH and CH. Decreased mitochondrial fission occurred during CH. Physiological relevance was established in skeletal muscle of mice with COPD that had increased phosphorylation of eIF2α, lower protein synthesis, and mitochondrial oxidative dysfunction. Molecular and metabolic responses with PIH suggests an adaptive exhaustion with failure to restore homeostasis during normoxia. Abstract figure legend Prolonged intermittent hypoxia (PIH) is commonly demonstrated in patients with COPD (chronic obstructive pulmonary disease); however, the effects of PIH on skeletal muscle are unclear. We tested the hypothesis that PIH causes skeletal muscle loss or sarcopenia in vitro by down-regulating protein synthesis and causing mitochondrial oxidative dysfunction associated with dysregulation of hypoxia inducible factors (HIF1α and HIF2α). α-ketoglutarate (αKG), a critical TCA cycle intermediate and co-factor for the degradation of HIF1α, was reduced due to PIH. Physiological relevance was established in skeletal muscle of mice with COPD. Our findings suggest that PIH causes sarcopenia through adaptive exhaustion and failure to restore homeostasis during normoxia. This article is protected by copyright. All rights reserved.

Class-switch recombination (CSR) produces secondary Ig isotypes and requires activation-induced cytidine deaminase (AID)–dependent DNA deamination of intronic switch regions within the IgH (Igh) gene locus. Noncanonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal switch regions. Ataxia telangiectasia mutated (ATM)–dependent phosphorylation of AID at serine 38 (pS38-AID) promotes its interaction with apurinic/apyrimidinic endonuclease 1 (APE1), a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm−/− mice were bred to mice deficient for the MMR gene mutS homolog 2 (Msh2). Surprisingly, the predicted Mendelian frequencies of Atm−/−Msh2−/− adult mice were not obtained. To generate ATM and MSH2-deficient B cells, Atm was conditionally deleted on an Msh2−/− background using a floxed ATM allele (Atmf) and B cell–specific Cre recombinase expression (CD23-cre) to produce a deleted ATM allele (AtmD). As compared with AtmD/D and Msh2−/− mice and B cells, AtmD/DMsh2−/− mice and B cells display a reduced CSR phenotype. Interestingly, Sμ–Sγ1 junctions from AtmD/DMsh2−/− B cells that were induced to switch to IgG1 in vitro showed a significant loss of blunt end joins and an increase in insertions as compared with wild-type, AtmD/D, or Msh2−/− B cells. These data indicate that the absence of both ATM and MSH2 blocks nonhomologous end joining, leading to inefficient CSR. We propose a model whereby ATM and MSH2 function cooperatively to regulate end joining during CSR through pS38-AID.

Efforts to reduce nitrogen dioxide (NOWe identified zip codes that had EPA monitors which monitored NOData from zip codes in Buffalo, Detroit, Phoenix, and Tucson from 2009 to 2011 demonstrated that the monthly mean NOPediatric admissions to the hospital for asthma exacerbations mirror the cyclic and seasonal pattern of NO

This article describes how redesigning a program's assessment practices for teaching with primary sources (TPS) can provide a clear framework for talking about the impact of educators' work in archives and can provide feedback on how to refine instruction practices for greater results. The authors share a description of their assessment redesign process accompanied by analysis of the implementation of our new assessment tool in the hope others will consider the design and goals of their own assessment practices. The authors' work demonstrates that reflection on existing tools, development of new goals, and design of new assessment strategies can yield inspiring new data on program impact and highlight areas for improvement. By illustrating the authors' redesign process, this article also demonstrates the types of impacts and outcomes that educators can measure for TPS and points to the huge potential of TPS in local history contexts and elsewhere. The authors' revised student assessment moved archives staff from relying on self-reported, affect-focused data to better understanding the outcomes of their work with students: the impact of project-based learning in archives; the value that students find in various aspects of their encounters with archives; the role that TPS in local history contexts plays in connecting students to their community; and the transferability of research skills that students learn through TPS activities.

In this interview, Professor Per Backlund shares his experience working for more than 20 years as a researcher and teacher in videogames. He outlines his initial interest in games, in the early 2000s, while completing a Ph.D. at Stockholm University and teaching part-time at the University of Skövde in Sweden. He shares how he moved from more general research in computer science and IT to a more specific focus on games, particularly on serious games and game-based learning issues. He also discusses his role as a teacher and Program Director in the very large games education (600+ students) at the University of Skövde, sharing the challenges of supporting interdisciplinary research. As founder and chair of the new Council for Swedish Games Researchers, he also describes the aims of the organization: to bring greater understanding to the specific needs of creating a sustainable Swedish ecosystem for game development. He explains the primary objectives of the Sweden Game Arena consortium, meant to promote Swedish game development in Skövde and beyond, and its newest initiative, via the recently-funded Level Up Swedish Game Industry (or Level Up) project, where he serves as university coordinator in the project management team. Finally, he speculates about the future needs for games and game research in rapidly developing and shifting technological and socio-cultural contexts for game-making and game research., gamevironments, No. 18 (2023)

Citizens everywhere have the right to be well-informed. Yet, with the high complexity of many contemporary issues, such as global warming and migration, our means of information need to mutually adapt. Narrative has always been at the core of information exchange - regardless of whether our ancestors sat around a fire and exchanged stories, or whether we read an article in a newspaper, or watched a TV news broadcast. Yet, the narrative formats of the newspaper article, the news broadcast, the documentary, and the textbook are severely limited when it comes to representing highly complex topics which may include several competing - and sometimes equally valid - perspectives. Such complexity contributes to a high level of uncertainty due to a multitude of factors affecting an outcome. Fortunately, with Interactive Digital Narrative (IDN), there is a novel media format which can address these challenges. IDNs can present several different perspectives in the same work, and give audiences the ability to explore them at will through decision-making. After experiencing the consequences of their decisions, the audience can replay to revisit and change these decisions in order to consider their alternatives. IDN works enable deep personalization and the inclusion of live data. These capabilities make IDN a 21st century democratic medium, empowering citizens through the understanding of complex issues. In this white paper, we discuss the challenge of representing complexity, describe the advantages offered by IDNs, and point out opportunities and strategies for deployment.

Background Previous research on whether feminist beliefs or self-identification are protective against body image disturbance and eating pathology in non-clinical populations has been variable. Further, no studies have examined feminism among those with diagnosed eating disorders. Additionally, feminist identity has yet to be examined in relation to weight stigma.Methods This study investigated if there are differences in body image, eating pathology, and weight stigma among feminist identity types in two samples using MANCOVAs. Participants completed self-report measures and were women with eating disorders (N = 100) and college women (N = 240).Results Sixty-four percent of the women with eating disorders and 75.8% of the college women identified as a feminist. An independent samples t-test found a significantly higher weight bias internalization in the clinical eating disorder sample than in the college women sample. A MANCOVA in the eating disorder sample found that feminists did not differ from non-feminists on weight bias internalization, body image, or eating pathology. In the college women sample, the MANCOVA also found no statistically significant differences between non-feminist and feminist women.Conclusions Results from this study suggest that sexism and weight stigma may function as self-sustainable systems of oppression. Findings highlight the need for further research investigating its weight bias internalization within eating disorder prevention efforts and interventions.

Background: Sarcopenia, or skeletal muscle loss, is common complication in COPD and contributes to adverse clinical outcomes including mortality. As the disease progresses, a significant proportion of COPD patients develop nocturnal hypoxemia which causes tissue-level hypoxia in the skeletal muscle which we have termed prolonged intermittent hypoxia (PIH). We have demonstrated sarcopenia, mitochondrial dysfunction, and dysregulated hypoxia-inducible factor 1-α (HIF1-α) responses both in vitro and in vivo in response to PIH. We also noted multiple transcriptional targets of HIF1-α were upregulated in the glycolytic pathway. We hypothesized that PIH upregulates the Hexosamine Biosynthetic (HB) pathway, a branch of glycolysis responsible for post-translational glycosylation of proteins, to cause O-GlcNAcylation of DRP1 leading to increased mitochondrial fission, fragmented mitochondrial networks, mitochondrial dysfunction, and sarcopenia. Methods: Our in vitro model of PIH exposed differentiated, murine C2C12 myotubes to 16h normoxia/8h hypoxia [1% oxygen] for 3 days, while our in vivo model exposed C57BL/6 mice to 12h normoxia/12h hypoxia [10% oxygen] for 21 days. Protein extraction and immunoblots were performed to probe for enzymes in the HB, mTORC1 pathways, O-GlcNAcylation, and puromycin incorporation. Imaging of mitochondrial structure was determined by staining with MitoTracker orange and electron microscopy. Immunoprecipitation and detection of Drp1 O-GlcNAcylation was performed by incubating protein lysates with Wheat Germ Agglutinin coated Agarose beads. To determine responses to inhibition of O-GlcNAcylation, we performed CRISPR-Cas9 RNP deletion of GFAT, the first enzyme in the HB pathway. Results: We found significant increase in O-GlcNAcylated proteins in our PIH models . This was accompanied by increased expression of HIF1-α, mitochondrial dysfunction, and upregulated enzymes in the HB pathway. O-GlcNAcylated modification of DRP1 was significantly upregulated due to PIH in vitro. GFAT KO myotubes demonstrated significant reductions in global O-GlcNAcylation of proteins and O-GlcNAcylated Drp1 with PIH. Interestingly, protein synthesis was rescued in GFAT KO myotubes as determined by puromycin incorporation, restoration of mTORC1 signaling, and reversal of a sarcopenic phenotype. Conclusion: Our findings demonstrate a potential mechanism for mitochondrial dysfunction and sarcopenia due to PIH which may be translationally relevant for patients with COPD. Future studies focused on O-GlcNAcylated modification of DRP1 and the functional consequences are needed to identify novel therapeutic targets to reverse sarcopenia in COPD. Supported in part by: NIH RO1 GM119174; RO1 DK113196; P50 AA024333; RO1 AA021890; 3U01AA026976 - 03S1; UO1 AA 026976; R56HL141744;UO1 DK061732; 5U01DK062470-17S2; R21 AR 071046; Howard and Helen Trevey Endowment; (SD); K12 HL141952 (AA) and the American College of Gastroenterology Clinical Research Award and NIH KO8 AAAA028794 (NW). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Subsea annulus seals are a critical part of a subsea wellhead system installation. The evolving need to achieve greater annulus pressure and extended lockdown performance is ever present while combined with the need to install in as timely an operation as possible. It is crucial to ensure reliable installation, coupled with the knowledge that the annulus seal is installed correctly to achieve the design performance as qualified in lab settings. This paper discusses the design and testing of a high pedigree subsea annulus seal utilized in challenging environmental conditions and discusses features introduced to the seal and installation tooling to ensure confidence in long term integrity of the system.

Though there have been significant developments in authoring tools for interactive narratives as well as a growing number of models explaining narrative meaning production, there is still a lack of understanding around what type of authoring support is required that can facilitate authors to handle the complex environment they develop by maintaining a high content and experience quality. In this paper, we present an investigation that aims to establish relations between individual information needs and navigation behaviour, which can be used as patterns to support authors in the design and development of interaction processes for Interactive Discourse Environments (IDE). A prototype of an argumentative discourse environment has been developed, in which participants can explore information resources in various media representations and complexity levels to gain better insights on climate change. The navigation behaviour has been tracked, and qualitative interviews have been performed to gain deeper insights in the relation between personal information needs, resource preferences and investigation behaviour. The findings of the analysis show that socio-cultural attributes can be identified that correlate to certain navigation patterns. We also show how those patterns can be made available as content and engine consistency checking devices in an IDE authoring environment.

CoWeb is a collaborative learning environment used in many classes at Georgia Institute of Technology; it is an extremely simple domain-independent collaboration tool. Our aim is to show that such a simple system can sustain useful peer-to-peer and instructor-to-student interaction that fosters better performance and learning, without incurring a high cost. In this paper, we present evidence of the success of this tool in supporting learning at low cost in one environment---freshman-level English classes.

This essay provides background for the workshop, rooted in research on how to support the decision-making of news users when reporting on the rapidly emerging scientific consensus about the COVID-19 pandemic. Specifically, we used data collected through the NewsHour/Knology partnership to test for reliable relationships between reported compliance with Centers for Disease Control and Prevention recommendations and judgements about protecting and/or promoting wellbeing at three social scales: me, those around me, and society as a whole.

Because people are constantly confronted with numbers and mathematical concepts in the news, we have embarked on a project to create journalism that can support news users’ number skills. But doing so requires understanding (1) journalists’ ability to reason with numbers, (2) other adults’ ability to do so, and (3) the attributes and affordances of news. In this paper, we focus on the relationship between adults’ news habits and their quantitative reasoning skills. We collected data from a sample of 1,200 US adults, testing their ability to interpret statistical results and asking them to report their news habits. The assessment we developed differentiated the skills of adults in our sample and conformed to the theoretical and statistical assumption that such skills are normally distributed in the population overall. We also found that respondents could be clustered into six distinct groups on the basis of news repertoires (overall patterns of usage, including frequency of news use overall and choice of news outlets). As often assumed in the literature on quantitative reasoning, these news repertoires predicted quantitative reasoning skills better than the amount of quantification in the outlets, but they still predicted only a small fraction of the variance. These results may suggest that news habits may play a smaller or less direct role in quantitative reasoning than has previously been assumed. We speculate that the presence (or absence) of quantification in everyday activities – namely work and hobbies – may be a better predictor of adults’ quantitative reasoning, as may additional dimensions of news habits and affective responses to numbers.

This white paper introduces Interactive Digital Narratives (IDN) as a powerful tool for tackling the complex challenges we face in today's society. In the scope of the COST Action 18230 - Interactive Narrative Design for Complexity Representation, a group of researchers dedicated to studying media, systematically selected six case studies of IDNs, including educational games, news media, and social media content, that confront and challenge the existing traditional media landscape. These case studies cover a wide range of important societal issues, such as racism, coloniality, feminist social movements, cultural heritage, war, and disinformation. By exploring this broad range of examples, we aim to demonstrate how IDN can effectively address social complexity in an interactive, participatory, and engaging manner. We encourage you to examine these case studies and discover for yourself how IDN can be used as a creative tool to address complex societal issues. This white paper might be inspiring for journalists, digital content creators, game designers, developers, educators using information and communication technologies in the classroom, or anyone interested in learning how to use IDN tools to tackle complex societal issues. In this sense, along with key scientific references, we offer key takeaways at the end of this paper that might be helpful for media practitioners at large, in two main ways: 1) Designing IDNs to address complex societal issues and 2) Using IDNs to engage audiences with complex societal issues.

Readmissions after hospitalizations for acute exacerbation of chronic obstructive pulmonary disease (COPD) have a high socioeconomic burden. Comorbidities such as diabetes increase the risk for hospital readmissions, but the impact of diabetes on hospital outcomes remains unknown. The aim of this study was to evaluate the effect of complicated or uncomplicated diabetes on outcomes and health care costs related to admissions and readmissions in patients 35 years and older with an index admission for COPD.This was a retrospective longitudinal data analysis. We analyzed data from the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmissions Database.We analyzed the 2012-2015 HCUP Nationwide Readmissions Database and used multivariable weighted regression analyses to adjust for confounding factors. Individuals with any chronic pulmonary disease other than COPD were excluded.Of 1,728,931 patients hospitalized for COPD, 522,020 (30.2%) had a diagnosis of diabetes. Risk of all-cause 30-day readmission was higher among patients with complicated diabetes (adjusted odds ratio [OR], 1.15; 95% CI, 1.11-1.18) and uncomplicated diabetes (adjusted OR, 1.10; 95% CI, 1.08-1.12) compared with patients without diabetes. Diabetes was associated with longer length of stay, higher rates of hospital complications during index hospitalizations and 30-day readmissions, and a higher health care cost. Although diabetes was not associated with higher hospital mortality, routine hospital discharges were less common and the need for home health care upon discharge was higher among those with diabetes.Patients hospitalized for COPD and coexisting diabetes have worse clinical outcomes and higher 30-day readmissions compared with patients hospitalized for COPD without diabetes. Optimizing medical therapies and targeted interventions for both diseases is needed to alleviate disease burden to individuals and to society.

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm-/- mice were bred to mice deficient for the MMR gene Msh2. Surprisingly, the predicted Mendelian frequencies of Atm-/-Msh2-/- adult mice were not obtained. To generate ATM and MSH2-deficient B cells, Atm was conditionally deleted on an Msh2-/- background using a floxed ATM allele [Atmf] and B cell-specific Cre recombinase expression (CD23-cre) to produce a deleted ATM allele (AtmD). As compared to AtmD/Dand Msh2-/- mice and B cells, AtmD/DMsh2-/- mice and B cells display a reduced CSR phenotype. Interestingly, Sμ-Sγ1 junctions from AtmD/DMsh2-/-B cells that were induced to switch to IgG1 in vitro showed a significant loss of blunt end joins and an increase in insertions as compared to wildtype, AtmD/D, or Msh2-/- B cells. This data indicates that the absence of both ATM and MSH2 blocks non-homologous end joining (NHEJ), leading to inefficient CSR. We propose a model whereby ATM and MSH2 function cooperatively to regulate end-joining during CSR through pS38-AID.SummaryLoss of the DNA repair genes Atm and Msh2 produces a novel synthetic lethality in mice. B cell specific deletion of Atm on an Msh2-/- background reduces Ig CSR and inhibits NHEJ.

BACKGROUND/AIMS: Signaling and metabolic perturbations contribute to dysregulated skeletal muscle protein homeostasis and secondary sarcopenia in response to a number of cellular stressors including ethanol exposure. Using an innovative multiomics-based curating of unbiased data, we identified molecular and metabolic therapeutic targets and experimentally validated restoration of protein homeostasis in an ethanol-fed mouse model of liver disease. METHODS: Studies were performed in ethanol-treated differentiated C2C12 myotubes and physiological relevance established in an ethanol-fed mouse model of alcohol-related liver disease (mALD) or pair-fed control C57BL/6 mice. Transcriptome and proteome from ethanol treated-myotubes and gastrocnemius muscle from mALD and pair-fed mice were analyzed to identify target pathways and molecules. Readouts including signaling responses and autophagy markers by immunoblots, mitochondrial oxidative function and free radical generation, and metabolic studies by gas chromatography-mass spectrometry and sarcopenic phenotype by imaging. RESULTS: Multiomics analyses showed that ethanol impaired skeletal muscle mTORC1 signaling, mitochondrial oxidative pathways, including intermediary metabolite regulatory genes, interleukin-6, and amino acid degradation pathways are β-hydroxymethyl-butyrate targets. Ethanol decreased mTORC1 signaling, increased autophagy flux, impaired mitochondrial oxidative function with decreased tricarboxylic acid cycle intermediary metabolites, ATP synthesis, protein synthesis and myotube diameter that were reversed by HMB. Consistently, skeletal muscle from mALD had decreased mTORC1 signaling, reduced fractional and total muscle protein synthesis rates, increased autophagy markers, lower intermediary metabolite concentrations, and lower muscle mass and fiber diameter that were reversed by β-hydroxymethyl-butyrate treatment. CONCLUSION: An innovative multiomics approach followed by experimental validation showed that β-hydroxymethyl-butyrate restores muscle protein homeostasis in liver disease.

Chronic disease causes skeletal muscle loss that contributes to morbidity and mortality. There are limited data on the impact of dynamic muscle loss on clinical outcomes in COVID-19. We hypothesized that acute COVID-19-related muscle loss (acute sarcopenia) is associated with adverse outcomes.A retrospective analysis of a prospective clinical registry of COVID-19 patients was performed in consecutive hospitalized patients with acute COVID-19 (n = 95) and compared with non-COVID-19 controls (n = 19) with two temporally unique CT scans. Pectoralis muscle (PM), erector spinae muscle (ESM) and 30 day standardized per cent change in cross sectional muscle area were quantified. Primary outcomes included mortality and need for intensive care unit (ICU) admission. Multivariate linear and logistic regression were performed. Cox proportional hazard ratios were generated for ICU admission or mortality for the per cent muscle loss standardized to 30 days.The COVID-19 CT scan cohort (n = 95) had an average age of 63.3 ± 14.3 years, comorbidities including COPD (28.4%) and diabetes mellitus (42.1%), and was predominantly Caucasian (64.9%). The proportion of those admitted to the ICU was 54.7%, with 10.5% requiring tracheostomy and overall mortality 16.8%. Median duration between CT scans was 32 days (IQR: 16-63 days). Significant reductions in median per cent loss was noted for PM (-2.64% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.01, -0.28] in non-COVID-19 CT controls, P 0.001) and ESM (-1.86% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.02, -0.11]) in non-COVID-19 CT controls, P 0.001). Multivariate linear regression analysis of per cent loss in PM was significantly associated with mortality (-10.8% loss [95% CI: -21.5 to -0.19]) and ICU admission (-11.1% loss [95% CI: -19.4 to -2.67]), and not significant for ESM. Cox proportional hazard ratios demonstrated greater association with ICU admission (adj HR 2.01 [95% CI: 1.14-3.55]) and mortality (adj HR 5.30 [95% CI: 1.19-23.6]) for those with significant per cent loss in PM, and greater association with ICU admission (adj HR 8.22 [95% CI: 1.11-61.04]) but not mortality (adj HR 2.20 [95% CI: 0.70-6.97]) for those with significant per cent loss in ESM.In a well-characterized cohort of 95 hospitalized patients with acute COVID-19 and two temporally distinct CT scans, acute sarcopenia, determined by standardized reductions in PM and ESM, was associated with worse clinical outcomes. These data lay the foundation for evaluating dynamic muscle loss as a predictor of clinical outcomes and targeting acute sarcopenia to improve clinical outcomes for COVID-19.

This paper discusses the design, development and testing of an optimized subsea wellhead annulus seal. Historically annulus seal qualification and validation testing requirements are defined in API 6A and API 17D requiring a PR2F temperature and pressure cyclic test program, and x3 lockdown load cycles. Throughout the operational life of a production subsea wellhead, the annulus seal can be subjected to many start-up and shut-down cycles, leading to substantially more lockdown load cycles on the annulus seal than initially validated (OTC-30784-MS). Traditionally, it has been left up to operators to define their own requirements over and above API. Operating conditions experienced by the annulus sealing system and the subsea wellhead equipment can be exceptionally challenging. Prior to landing and locking the annulus sealing system in place, the sealing surfaces of both the wellhead system and the annulus seal are subjected to a multitude of operational and environmental conditions such as cuttings/ debris from circulating well fluids, possible damage from lowering the annulus seal through several thousand feet of subsea riser and a BOP stack and misalignment of the seal during installation. The annulus sealing system of the subsea wellhead equipment is a critical secondary well barrier for well control. Either in exploration or production mode, with the casing cemented in place, the annulus sealing system locks the subsea casing hanger into position, providing a metal-to-metal seal across the annulus of the intermediate casing. The purpose of the annulus sealing system is to ensure it does not unseat and lose integrity in the event there is any pressure from below the seal due to a leak, reduced hydrostatic pressure from above or from thermal expansion during the production life of the well.

COPD is a common respiratory disorder that poses a major health-care burden with societal and financial ramifications. Although effective inhaled therapies are available, nonadherence is common among patients with COPD and potentially contributes to the burden of this disease. Electronic inhaler monitoring (EIM) is a novel modality that enables real-time assessment of adherence to inhaled therapy and informs the assessment of treatment effectiveness. EIM can be combined with physician feedback, automated audiovisual reminders, and text messaging to bolster adherence. Clinical studies have suggested that EIM can diagnose nonadherence, improve adherence, and predict exacerbations. Using an EIM-guided protocol has the potential to avoid treatment escalation in the nonadherent. Coupling EIM to behavioral intervention is an area of ongoing research with mixed results, with some studies showing benefit and others showing minimal or no significant change in clinical outcomes. Further investigation is necessary to understand the incremental benefits of EIM features, delineate optimal program implementation, and target patient populations that would benefit the most from monitoring.

This article examines historical examples to illuminate a prehistory of the interactive reader in analogue media, tracing a rich genealogy that is helpful for understanding and designing current works such as augmented reality (AR) books. In addition, a set of generative design strategies to help shape current practice are discussed, based both on formal qualities and characteristics of historical examples and the authors’ own experiences as designers working in mixed reality over many years. Theoretical framing is provided to persuasively make the case for the relevance of historical works for designers today. From medieval manuscripts, to Renaissance medical texts, to seventeenth, eighteenth and nineteenth century movable books, to the elaborate paper engineering of twentieth century and contemporary pop-up books, the history of the active reader and interactive book design is long and fascinating, and is presented here as an important and direct source of inspiration for digital designers today. Finally, recent interactive book projects designed by the authors are discussed and analyzed for both continuities and disruptions of historical interactive book design strategies, and a framework is presented for conceptualizing the postdigital interactive reader today.

Informal learning institutions--museums, libraries, news organizations, and others--figure prominently in the ecosystem of lifelong learning ( Gupta et al. 2020). These institutions work to inform their audiences about the rapidly emerging scientific consensus on various topics. Often this information invites action, such as avoiding single-use plastic, watering lawns and gardens at dawn or dusk to conserve water, or social distancing during a pandemic. What motivates people to act upon that information (or not)? One answer from social psychological theory is that people are motivated by a desire to protect and care for their family, friends, and perhaps society as a whole--i.e., moral motives. Knology often partners with informal learning institutions to provide theory-driven answers to such questions. With the Moral Motives Conference, we are taking this a step further by bringing together social science theorists and science communicators from informal learning institutions. The goal is to have them talk directly to each other about what questions matter most for science communication and what answers theoretical research might provide. The Moral Motives Conference has its origins in NSF-funded research by the PBS NewsHour/Knology Participatory Action Research Lab. It is part of the grant-funded research on how to support the decision-making of news users when reporting on the rapidly emerging scientific consensus about the COVID-19 pandemic. Specifically, we used data collected through the NewsHour/Knology partnership to test for reliable relationships between reported compliance with Centers for Disease Control and Prevention recommendations and judgements about protecting and/or promoting wellbeing at three social scales: me, those around me, and society as a whole. The results aligned with theoretical predictions and prompted us to ask whether moral motives -- social obligations, needs, and desires -- might be implicated more broadly in STEM learning, STEM-informed decision-making, and STEM-informed action. This conference is about exploring how moral motives move people from STEM information learning to STEM-informed action. Public health behavior is one sliver of STEM-informed action and the recommendations we examined represent only a narrow portion of that sliver. In this article, we present our preliminary findings to start a conversation. The range of conference participants should broaden the basis of that conversation, and help us get a sense of the motives (moral or non-moral) for STEM-informed action in a range of STEM topic areas.

In this paper we look at examples of creative, emergent and performative practices in readership. Starting with the history of the book, and including a discussion of a range of reader practices we make connections with our own creative practice as designers of interactive mixed reality movable books today. A theoretical frame for characterizing the reader today as postdigital is presented to push back against commonly held beliefs about the act of reading as passive or somehow less creative or enacted compared with digital technologies. Finally, our own interactive movable book project Simmer is discussed as a means to bridge historical methods and materials with the digital, and a set of design strategies are provided in support of postdigital readership. CC BY 4.0Published: 2022-04-01

Games are trouble. As faculty members in a Game Development program we are aware of the troubles. As inside–outsiders, given our status as queer women in the male-dominated Games field, both with interdisciplinary art-tech-humanities backgrounds as opposed to STEM, we are the ones commonly tasked with ‘fixing’ these troubles. This tasking comes to us in the form of both assumptions and requests about our providing particular types of education to others, both faculty and students, as fixes to Game-troubles: teaching the gender module; sitting on an LGBTQ+ committee; advising a particular student who is also outside the more comfortable purview of Games; and so forth. While our labor is often assumed, it is not fully valued, evidenced by the ways in which it is chronically under-resourced. And, given this lack of sustainability, our labor is not effective in the ways we intend. Often, our fixes only serve to a fix ourselves, further cementing us as outsiders. Our fixes are diluted until they become performative gestures, absolving others of the need to act, but changing little else. Acting ‘in a fix’ is something we no longer wish to do. Instead we untangle and re-tangle in a new way, drawing on the work of Feminist New Materialists (Ahmed, 2008; Alaimo, 2016; Alaimo and Hekman, 2008; Barad, 2011; Bennett, 2010; Braidotti, 2013; Coole and Frost, 2010; Dolphijn and Tuin, 2012; Grosz, 1994; Kirby, 1997) to develop imaginative new models for a more just and joyful future Games pedagogy. We share not only our research on this topic, but also invite you into our own intimate experiences of play-making, foregrounding this as knowledge-making too. We offer these crossings between text and context, history and future Ahmed, 2008, memory and fiction as a speculative fabulation for future Games pedagogies. CC BY 4.0First Published February 22, 2022Corresponding Author: Rebecca Rouse, Department of Game Development, University of Skövde, Kanikegränd 3A, Skövde 541 28, Sweden. Email: rebecca.rouse@his.se

In this article, we reflect on the design and implementation of an interactive transhistorical and transmedial web-based digital narrative audio experience, PATTER(n)INGS: Apt 3B, 2020 that we developed in 2020. This work is an immersive audio-only application, and it focuses on the complex, material living conditions during the COVID-19 pandemic. Drawing inspiration from PATTER(n)INGS and its complex, material audio and narrative design, we propose a model for creating the content and delivery for similar sound-based interactive digital narratives. Our proposed model focuses primarily on the creative process for designing such sound-based work. To construct our analytical model, the New Material/Spectral Morphology Design Model (or NM/SM Design Model), we draw on theoretical influences from critical posthumanism, feminist new materialism and non-human narrative that critique notions of stable subjectivity as sites for power and authority over semiotic meaning-making. We combine these views with foundational theoretical research in electroacoustic musical composition notation, and audio experimentation that complicate notions of sound, sound making, spatial perception, psychoacoustic phenomena, and listening practices. Together, this theoretical/compositional framework provides a unique method to consider how one can sustain and maximize sonic agents as core phenomena to create anti-cognitive worlds and stories. CC BY-NC-ND 4.0Received 19 Aug 2022, Accepted 30 Jan 2023, Published online: 14 Feb 2023Taylor & Francis Group an Informa businessCONTACT Lissa Holloway-Attaway lissa.holloway-attaway@his.se Division of Game Development, University of Skövde, Skövde, 541 28, SwedenThe work presented in this text has been partially supported by the EU COST Action 18230—Interactive Narrative Design for Complexity Representation (INDCOR) and the GAMEResearch Group at University of Skövde, Sweden.

The news arguably serves to inform the quantitative reasoning (QR) of news audiences. Before one can contemplate how well the news serves this function, we first need to determine how much QR typical news stories require from readers. This paper assesses the amount of quantitative content present in a wide array of media sources, and the types of QR required for audiences to make sense of the information presented. We build a corpus of 230 US news reports across four topic areas (health, science, economy, and politics) in February 2020. After classifying reports for QR required at both the conceptual and phrase levels, we find that the news stories in our sample can largely be classified along a single dimension: The amount of quantitative information they contain. There were two main types of quantitative clauses: those reporting on magnitude and those reporting on comparisons. While economy and health reporting required significantly more QR than science or politics reporting, we could not reliably differentiate the topic area based on story-level requirements for quantitative knowledge and clause-level quantitative content. Instead, we find three reliable clusters of stories based on the amounts and types of quantitative information in the news stories.

Dysfunctional interoceptive processing of hunger and satiety cues is particularly relevant to disordered eating behaviors. However, researchers often rely on general measures of interoceptive sensibility (IS

Background and Aims Overreliance on opioids to treat postoperative pain and increased availability of opioids in the community have contributed to the opioid epidemic (1). For many patients, the source of initial exposure to opioids is the perioperative period. The aim of this project was to identify local practice and introduce ways to minimise opioids during anaesthesia and recovery. Methods We conducted a two-week snapshot audit in November 2019 at Brighton and Sussex University Hospitals (BSUH) (UK). The audit was registered with BSUH anaesthetic department Audit and Quality Improvement. Ethics approval was not required. We collected data on opioid use in four theatres and recovery. We also conducted a literature search to identify best available evidence on non-opioid adjuncts. Results Median opioid use in each theatre and recovery are presented in table 1. In recovery, 1 in 3 patients required more than 10 mg intravenous morphine equivalents (IVME), and more than 1 in 10 patients received more than 20 mg IVME. We compiled evidence-based opioid sparing anaesthesia and analgesia guides for use in theatres and recovery (Figure 1). Conclusions Although there are no standards to compare with, we believe that these results indicate high opioid use during anaesthesia and recovery. The risk of opioid dependence and side effects that may adversely affect surgical outcomes should be taken into account before prescribing opioids. There is a plethora of non-opioid adjuncts which may facilitate opioid-free or opioid-light anaesthesia and analgesia. Further work is required to investigate if anaesthesia and recovery opioid sparing protocols can improve patient outcomes.