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Informal science learning centers (ISLCs) like zoos, aquariums and botanic gardens are trusted community assets and perceived as critical sites for learning outside the classroom for multigenerational learners. Moreover, their role in engaging the public in critical topics, such as climate change is widely recognized. As extreme weather events grow more frequent, building climate resilient social and ecological systems will be necessary. However, how ISLCs facilitate climate resilience is understudied. This paper presents findings from two qualitative case studies of climate resilience projects, through partnerships between community organizations and ISLCs. The results demonstrated the need to prioritize relationship building so that organizations with distinct approaches authentically appreciate each other's work and foster power symmetries. Diverse definitions of 'resilience' emerged, where ecological and social resilience held unique meaning for residents most vulnerable to climate events. Ultimately, the research highlighted how ISLCs and community partners can advance equitable and inclusive climate resilience. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e., sarcopenia) in in vitro models of COPD. Objectives: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in patients with COPD. Methods: Sleep studies from patients with COPD (n = 479) and control subjects without COPD (n = 275) were analyzed. Patients with obstructive sleep apnea, as defined by apnea–hypopnea index ⩾ 5, were excluded. Pectoralis muscle cross-sectional area (PMcsa) was quantified using computed tomography scans performed within 1 year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of control subjects, which was adjusted for age and body mass index (BMI) and stratified by sex. Youden's optimal cut-point criteria were used to predict sarcopenia based on mean oxygen saturation during sleep. Additional measures of nocturnal hypoxemia were analyzed. The pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. Results: On average, males with COPD had a 16.6% lower PMI than control males (1.41 ± 0.44 vs. 1.69 ± 0.56 cm2/BMI; P < 0.001), whereas females with COPD had a 9.4% lower PMI than control females (0.96 ± 0.27 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). Males with COPD with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33 ± 0.39 vs. 1.47 ± 0.46 cm2/BMI; P < 0.05) and a 23.6% decrease compared with control subjects (1.33 ± 0.39 vs. 1.74 ± 0.56 cm2/BMI; P < 0.001). Females with COPD with nocturnal hypoxemia had an 11.2% decrease versus COPD with normal O2 (0.87 ± 0.26 vs. 0.98 ± 0.28 cm2/BMI; P < 0.05) and a 17.9% decrease compared with control subjects (0.87 ± 0.26 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. Conclusions: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that patients with COPD have a lower PMI than patients without COPD and that nocturnal hypoxemia was associated with an additional decrease in the PMI of patients with COPD. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD. [ABSTRACT FROM AUTHOR]

Numbers don't speak for themselves – yet taking numbers for granted (numerism) is widespread. In fact, journalists often rely heavily on numbers precisely because they are widely considered objective. As a team of journalists and social scientists, we undertook a qualitative exploration of clauses and entire news reports that are particularly quantitatively dense. The dense clauses were often grammatically complex and assumed familiarity with sophisticated concepts. They were rarely associated with explanations of data collection methods. Meanwhile, the dense news reports were all about economy or health topics, chiefly brief updates on an ongoing event (e.g., stock market fluctuations; COVID-19 cases). We suggest that journalists can support public understanding by: Providing more detail about research methods; Writing shorter, clearer sentences; Providing context behind statistics; Being transparent about uncertainty; and Indicating where consensus lies. We also encourage news organizations to consider structural changes like rethinking their relationship with newswires and working closely with statisticians. [ABSTRACT FROM AUTHOR]

Objective: Commonly used terms like "obese person" have been identified as stigmatizing by those with lived experience. Thus, this study sought to revise a commonly used measure of weight stigmatizing attitudes, the Attitudes Toward Obese Persons (ATOP) scale. Methods: The original terminology in the 20‐item ATOP (e.g., "obese") was compared to a modified version using neutral terms (e.g., "higher weight"). Participants (N = 832) were randomized to either receive the original or modified ATOP. Results: There was a statistically significant difference, with a small effect size (d = −0.22), between the scores of participants who received the original ATOP (M = 69.25) and the modified ATOP (M = 72.85), t(414) = −2.27, p = 0.024. Through principal component analysis, the modified ATOP was best used as a brief, 8‐item unidimensional measure. In a second sample, confirmatory factor analysis verified the fit of the brief, 8‐item factor structure. Conclusions: Findings suggest that a modified, brief version of the ATOP (ATOP‐Heigher Weight; ATOP‐HW) with neutral language is suitable for assessing negative attitudes about higher‐weight people. The ATOP‐HW may slightly underestimate weight stigma compared to the original ATOP, or the language in the ATOP may magnify negative attitudes. Further examination of the terminology used in weight stigma measures is needed to determine how to best assess weight stigma without reinforcing stigmatizing attitudes. The present study's findings suggest that the use of neutral terms in measures of anti‐fat bias is a promising solution that warrants further investigation. [ABSTRACT FROM AUTHOR]

Transceptors, solute transporters that facilitate intracellular entry of molecules and also initiate intracellular signaling events, have been primarily studied in lower-order species. Ammonia, a cytotoxic endogenous metabolite, is converted to urea in hepatocytes for urinary excretion in mammals. During hyperammonemia, when hepatic metabolism is impaired, nonureagenic ammonia disposal occurs primarily in skeletal muscle. Increased ammonia uptake in skeletal muscle is mediated by a membrane-bound, 12 transmembrane domain solute transporter, Rhesus blood group-associated B glycoprotein (RhBG). We show that in addition to its transport function, RhBG interacts with myeloid differentiation primary response-88 (MyD88) to initiate an intracellular signaling cascade that culminates in activation of NFκB. We also show that ammonia-induced MyD88 signaling is independent of the canonical toll-like receptor-initiated mechanism of MyD88-dependent NFκB activation. In silico, in vitro, and in situ experiments show that the conserved cytosolic J-domain of the RhBG protein interacts with the Toll-interleukin-1 receptor (TIR) domain of MyD88. In skeletal muscle from human patients, human-induced pluripotent stem cell-derived myotubes, and myobundles show an interaction of RhBG-MyD88 during hyperammonemia. Using complementary experimental and multiomics analyses in murine myotubes and mice with muscle-specific RhBG or MyD88 deletion, we show that the RhBG-MyD88 interaction is essential for the activation of NFkB but not ammonia transport. Our studies show a paradigm of substrate-dependent regulation of transceptor function with the potential for modulation of cellular responses in mammalian systems by decoupling transport and signaling functions of transceptors. [ABSTRACT FROM AUTHOR]

Introduction: The foundational practices of Computational Thinking (CT) present an interesting overlap with neurodiversity, specifically with differences in executive function (EF). An analysis of CT teaching and learning materials designed for differentiation and support of EF show promise to reveal problem-solving strengths of neurodivergent learners. Methods: To examine this potential, studies were conducted using a computersupported, inclusive, and highly interactive learning program named INFACT that was designed with the hypothesis that all students, including neurodivergent learners, will excel in problem solving when it is structured through a variety of CT activities (including games, puzzles, robotics, coding, and physical activities) and supported with EF scaffolds. The INFACT materials were used in 12 treatment classrooms in grades 3-5 for at least 10 h of implementation. Pre-post assessments of CT were administered to treatment classes as well as 12 comparison classes that used 10 h of other CT teaching and learning materials. EF screeners were also used with all classes to disaggregate student results by quartile of EF. Findings: Students using INFACT materials showed a significant improvement in CT learning as compared to comparison classes. Students with EF scores in the lower third of the sample showed the greatest improvement. Discussion: This study shows promising evidence that differentiated activities with EF scaffolds situated across several contexts (e.g., games, puzzles, physical activities, robotics, coding) promote effective CT learning in grades 3-5. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with systemic consequences that can cause a muscle loss phenotype (MLP), which is characterized by the loss of muscle mass, muscle strength, or loss of both muscle and fat mass. There are limited data comparing the individual traits of MLP with clinical outcomes in a large unbiased cohort of COPD patients. Our aim was to determine the proportion of patients who met criteria for MLP in an unbiased sample of COPD patients at the population-level. We also determined if specific MLP features were associated with all-cause and COPD-related mortality. Methods: A retrospective population-based cohort analysis of the UK Biobank was performed. COPD was defined by a FEV1/FVC ratio < 0.7, physician established diagnosis of COPD, or those with a COPD-related hospitalization before baseline assessment. MLP included one or more of the following: 1) Low fat-free mass index (FFMI) on bioelectric impedance analysis (BIA) or 2) Appendicular skeletal muscle index (ASMI) on BIA, 3) Low muscle strength defined by handgrip strength (HGS), or 4) Low muscle and fat mass based on body mass index (BMI). Cox regression was used to determine the association between MLP and all-cause or COPD-related mortality. All models were adjusted for sex, age at assessment, ethnicity, BMI, alcohol use, smoking status, prior cancer diagnosis and FEV1/FVC ratio. Results: There were 55,782 subjects (56% male) with COPD followed for a median of 70.1 months with a mean(± SD) age at assessment of 59 ± 7.5 years, and FEV1% of 79.2 ± 18.5. Most subjects had mild (50.4%) or moderate (42.8%) COPD. Many patients had evidence of a MLP, which was present in 53.4% of COPD patients (34% by ASMI, 26% by HGS). Of the 5,608 deaths in patients diagnosed with COPD, 907 were COPD-related. After multivariate adjustment, COPD subjects with MLP had a 30% higher hazard-ratio for all-cause death and 70% higher hazard-ratio for COPD-related death. Conclusions: Evidence of MLP is common in a large population-based cohort of COPD and is associated with higher risk for all-cause and COPD-related mortality. [ABSTRACT FROM AUTHOR]

Background: Hospitalization and mortality in patients with alcohol‐associated hepatitis (AH), a severe form of liver disease, continue to increase over time. Given the severity of the illness, most hospitalized patients with AH are admitted from the emergency department (ED). However, there are no data on ED utilization by patients with AH. Thus, the Nationwide Emergency Department Sample (NEDS) dataset was analyzed to determine the ED utilization for AH. Methods: Temporal trends (2016–2019) and outcomes of ED visits for AH were determined. Primary or secondary AH diagnoses were based on coding priority. Numbers of patients evaluated in the ED, severity of disease, complications of liver disease, and discharge disposition were analyzed. Crude and adjusted rates were examined, and temporal trends evaluated using logistic regression with orthogonal polynomial contrasts for each year. Results: There were 466,014,370 ED visits during 2016–2019, of which 448,984 (0.096%) were for AH, 85.0% of which required hospitalization. The rate of visits for AH (primary and secondary) between 2016 and 2019 increased from 85 to 106.8/100,000 ED visits. The rate of secondary AH increased more than the rate of primary AH (from 68.6 to 86.5 vs. from 16.4 to 20.3/100,000 ED visits). Patients aged 45–64 years had the highest rate of ED visits for AH, which decreased during the study period, while the rate of ED visits for AH increased in those aged 25–44 years (from 38.5% to 42.9%). The severity of disease (ascites, hepatic encephalopathy, and acute kidney injury) also increased over time. Medicaid and private insurance were the most common payors for patients seeking care in the ED for AH. Conclusions: Temporal trends show an overall increase in ED utilization rates for AH, more patients requiring hospitalization, and an increase in the proportion of younger patients presenting to the ED with AH. [ABSTRACT FROM AUTHOR]

Sarcopenia, defined as the loss of muscle mass and strength, is a major cause of morbidity and mortality in COPD (chronic obstructive pulmonary disease) patients. However, the molecular mechanisms that cause sarcopenia remain to be determined. In this review, we will highlight the unique molecular and metabolic perturbations that occur in the skeletal muscle of COPD patients in response to hypoxia, and emphasize important areas of future research. In particular, the mechanisms related to the glycolytic shift that occurs in skeletal muscle in response to hypoxia may occur via a hypoxia-inducible factor 1-alpha (HIF-1α)-mediated mechanism. Upregulated glycolysis in skeletal muscle promotes a unique post-translational glycosylation of proteins known as O-GlcNAcylation, which further shifts metabolism toward glycolysis. Molecular changes in the skeletal muscle of COPD patients are associated with fiber-type shifting from Type I (oxidative) muscle fibers to Type II (glycolytic) muscle fibers. The metabolic shift toward glycolysis caused by HIF-1α and O-GlcNAc modified proteins suggests a potential cause for sarcopenia in COPD, which is an emerging area of future research. [ABSTRACT FROM AUTHOR]

The article focuses on the legislative process and implications of House Bill 129, which expands Temporary Assistance for Needy Families (TANF) eligibility criteria to include pregnant women in Georgia. It discusses the background of TANF, the history of welfare policy in Georgia, the provisions and amendments made by HB 129, and the considerations and passage of the bill through both the House and the Senate.

Background: Research yields mixed results on whether feminist beliefs or self-identification are protective against body image disturbance and eating pathology in non-clinical populations. Further, no studies have examined feminism among those with diagnosed eating disorders. Additionally, previous studies have not examined the relationship between feminist identity and weight stigma. This study investigated these relationships and if there are differences in body image, eating pathology, and weight stigma among feminist identity types in women with eating disorders and college women using ANCOVAs. Methods: 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. No significant interactions were found between sample type and feminist identity for body image or weight bias internalization. Results were consistent when using a dichotomous feminist identity item and a seven-item continuous feminist identity item. Conclusions: Despite the clear impacts of the intersection of weight status and gender, results from this study suggest that identifying as a feminist is not sufficient to combate weight stigma. Findings highlight the need for further research investigating weight bias internalization within eating disorder prevention efforts and interventions. Plain English summary: Research shows mixed findings on whether feminist identity is protective against disordered eating and body image concerns. Those with diagnosed eating disorders (EDs) have not been included in previous Research examining the relationship between feminism and the severity of body image symptoms has not included those with diagnosed eating disorders (EDs). Thus, this study examined rates of feminist identity and beliefs in both women with EDs and college women, along with comparing the feminist/non-feminists and ED women/college women on eating disorder-related symptoms. We found that feminist and non-feminist college women and women with EDs did not have different rates of symptom endorsements. Internalization of weight stigmatizing beliefs is known as weight bias internalization (WBI), which means one holds negative beliefs about oneself based on one's weight. WBI also did not differ between feminists and non-feminists in either sample, but we did find that women with EDs endorsed higher WBI than college women. Given the health implications of weight stigma, our findings highlight the need for further research investigating WBI within ED prevention efforts and interventions. [ABSTRACT FROM AUTHOR]

Perturbed metabolism of ammonia, an endogenous cytotoxin, causes mitochondrial dysfunction, reduced NAD+/NADH (redox) ratio, and postmitotic senescence. Sirtuins are NAD+‐dependent deacetylases that delay senescence. In multiomics analyses, NAD metabolism and sirtuin pathways are enriched during hyperammonemia. Consistently, NAD+‐dependent Sirtuin3 (Sirt3) expression and deacetylase activity were decreased, and protein acetylation was increased in human and murine skeletal muscle/myotubes. Global acetylomics and subcellular fractions from myotubes showed hyperammonemia‐induced hyperacetylation of cellular signaling and mitochondrial proteins. We dissected the mechanisms and consequences of hyperammonemia‐induced NAD metabolism by complementary genetic and chemical approaches. Hyperammonemia inhibited electron transport chain components, specifically complex I that oxidizes NADH to NAD+, that resulted in lower redox ratio. Ammonia also caused mitochondrial oxidative dysfunction, lower mitochondrial NAD+‐sensor Sirt3, protein hyperacetylation, and postmitotic senescence. Mitochondrial‐targeted Lactobacillus brevis NADH oxidase (MitoLbNOX), but not NAD+ precursor nicotinamide riboside, reversed ammonia‐induced oxidative dysfunction, electron transport chain supercomplex disassembly, lower ATP and NAD+ content, protein hyperacetylation, Sirt3 dysfunction and postmitotic senescence in myotubes. Even though Sirt3 overexpression reversed ammonia‐induced hyperacetylation, lower redox status or mitochondrial oxidative dysfunction were not reversed. These data show that acetylation is a consequence of, but is not the mechanism of, lower redox status or oxidative dysfunction during hyperammonemia. Targeting NADH oxidation is a potential approach to reverse and potentially prevent ammonia‐induced postmitotic senescence in skeletal muscle. Since dysregulated ammonia metabolism occurs with aging, and NAD+ biosynthesis is reduced in sarcopenia, our studies provide a biochemical basis for cellular senescence and have relevance in multiple tissues. [ABSTRACT FROM AUTHOR]

Background: Patients with acute alcohol‐associated hepatitis (AH) have immune dysfunction. Mitochondrial function is critical for immune cell responses and regulates senescence. Clinical translational studies using complementary bioinformatics‐experimental validation of mitochondrial responses were performed in peripheral blood mononuclear cells (PBMC) from patients with AH, healthy controls (HC), and heavy drinkers without evidence of liver disease (HD). Methods: Feature extraction for differentially expressed genes (DEG) in mitochondrial components and telomere regulatory pathways from single‐cell RNAseq (scRNAseq) and integrated 'pseudobulk' transcriptomics from PBMC from AH and HC (n = 4 each) were performed. After optimising isolation and processing protocols for functional studies in PBMC, mitochondrial oxidative responses to substrates, uncoupler, and inhibitors were quantified in independent discovery (AH n = 12; HD n = 6; HC n = 12) and validation cohorts (AH n = 10; HC n = 7). Intermediary metabolites (gas‐chromatography/mass‐spectrometry) and telomere length (real‐time PCR) were quantified in subsets of subjects (PBMC/plasma AH n = 69/59; HD n = 8/8; HC n = 14/27 for metabolites; HC n = 13; HD n = 8; AH n = 72 for telomere length). Results: Mitochondrial, intermediary metabolite, and senescence‐regulatory genes were differentially expressed in PBMC from AH and HC in a cell type–specific manner at baseline and with lipopolysaccharide (LPS). Fresh PBMC isolated using the cell preparation tube generated optimum mitochondrial responses. Intact cell and maximal respiration were lower (p ≤.05) in AH than HC/HD in the discovery and validation cohorts. In permeabilised PBMC, maximum respiration, complex I and II function were lower in AH than HC. Most tricarboxylic acid (TCA) cycle intermediates in plasma were higher while those in PBMC were lower in patients with AH than those from HC. Lower telomere length, a measure of cellular senescence, was associated with higher mortality in AH. Conclusion: Patients with AH have lower mitochondrial oxidative function, higher plasma TCA cycle intermediates, with telomere shortening in nonsurvivors. [ABSTRACT FROM AUTHOR]

Background: Law enforcement agencies in the US have provided naloxone to officers and developed initiatives to follow-up after a non-fatal overdose. However, the prevalence and characteristics of these efforts have yet to be documented in research literature. Objectives: We sought to understand the national prevalence of naloxone provision among law enforcement and examine the implementation of post-overdose follow-up. Methods: We administered a survey on drug overdose response initiatives using a multimodal approach (online and mail) to a nationally representative sample of law enforcement agencies (N = 2,009; 50.1% response rate) drawn from the National Directory of Law Enforcement Administrators database. We further examine a subsample of agencies (N = 1,514) that equipped officers with naloxone who were also asked about post-overdose follow-up. Results: We found 81.7% of agencies reported officers were equipped with naloxone; among these, approximately one-third (30.3%) reported follow-up after an overdose. More than half (56.8%) of agencies indicated partnership in follow-up with emergency medical services as the most common partner (68.8%). There were 21.4% of agencies with a Quick Response Team, a popular national post-overdose model, and were more likely to indicate partnership with a substance use disorder treatment provider than when agencies were asked generally about partners in follow-up (74.5% and 26.2% respectively). Conclusion: Many law enforcement agencies across the US have equipped officers with naloxone, and about one-third of those are conducting follow-up to non-fatal overdose events. Post-overdose follow-up models and practices vary in ways that can influence treatment engagement and minimize harms against persons who use drugs. [ABSTRACT FROM AUTHOR]

Nocturnal hypoxaemia, which 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 apnoea (OSA). Adaptive cellular responses to PIH are not known. Responses to PIH induced by three cycles of 8 h hypoxia followed by 16 h normoxia were compared to those during chronic hypoxia (CH) or normoxia for 72 h 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, and of 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 suggest an adaptive exhaustion with failure to restore homeostasis during normoxia. 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 the pathophysiological relevance of our studies.These data lay the foundation for translational studies in human COPD to target prolonged, nocturnal hypoxaemia to prevent sarcopenia in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officer's perspective, including what officers perceive their duties and responsibilities to be as the incident evolves. Methods: The qualitative study examined officers' experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020. Results: Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia. Conclusion: These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

B cells play a significant role in the adaptive immune response by secreting immunoglobulins that can recognize and neutralize foreign antigens. They develop from hematopoietic stem cells, which also give rise to other types of blood cells, such as monocytes, neutrophils, and T cells, wherein specific transcriptional programs define the commitment and subsequent development of these different cell lineages. A number of transcription factors, such as PU.1, E2A, Pax5, and FOXO1, drive B cell development. Mounting evidence demonstrates that non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), modulate the expression of these transcription factors directly by binding to the mRNA coding for the transcription factor or indirectly by modifying cellular pathways that promote expression of the transcription factor. Conversely, these transcription factors upregulate expression of some miRNAs and lncRNAs to determine cell fate decisions. These studies underscore the complex gene regulatory networks that control B cell development during hematopoiesis and identify new regulatory RNAs that require additional investigation. In this review, we highlight miRNAs and lncRNAs that modulate the expression and activity of transcriptional regulators of B lymphopoiesis and how they mediate this regulation. [ABSTRACT FROM AUTHOR]

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs). [ABSTRACT FROM AUTHOR]

Objectives: Skeletal muscle loss or sarcopenia is a frequent complication in heart failure (HF) and contributes to adverse clinical outcomes. We evaluated if age (primary) and chronic disease (secondary) related sarcopenia, that we refer to as compound sarcopenia, impacts clinical outcomes in hospitalized patients with HF. Design: Cross‐sectional study using hospitalized patient data. Setting: Data from the Agency for Healthcare Research and Quality through the Healthcare Cost and Utilization Project (HCUP). Participants: Hospitalized adult patients with a primary or secondary diagnosis of HF (n = 64,476) and a concurrent random 2% sample of general medical population (GMP; n = 322,217) stratified by age (<50 years of age [y], 51‐65y, >65y) from the Nationwide Inpatient Sample (NIS) database (years 2010–2014). Measurements: In‐hospital mortality, length of stay (LoS), cost of hospitalization per admission (CoH), comorbidities and discharge disposition, with and without muscle loss phenotype, were analyzed. Muscle loss phenotype was defined using a comprehensive code set from international classification of diseases‐9 (ICD‐9). Results: Muscle loss phenotype was observed in 8673 (13.5%) patients with HF compared to 5213 (1.6%) GMP across all age strata. In patients with HF, muscle loss phenotype was associated with higher mortality, LoS, and CoH. Patients with HF (>65y) and muscle loss phenotype had higher mortality (adjusted OR: 1.81; 95% CI 1.56–2.10), CoH (adjusted OR 1.48; 95% CI 1.44–1.1.52), and LoS (adjusted OR 1.40; 95% CI 1.37–1.43) compared to >65y GMP with muscle loss phenotype. Conclusion: Muscle loss phenotype is more commonly associated with increasing age in hospitalized patients with HF. Clinical outcomes were significantly worse in patients with HF aged >65y compared to younger patients with HF and all age strata in GMP with and without a muscle loss phenotype. See related editorial by Reeves et al. in this issue. [ABSTRACT FROM AUTHOR]

Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD. This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020. Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes. Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease. Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033). Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80). Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90–1.38), ICU admission (adj OR: 1.31, CI: 0.82–2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69–4.02), or mortality (OR: 0.80, CI: 0.43–1.49). In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system. These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Asthma exacerbations result in significant health and economic burden, but are difficult to predict.Research Question: Can machine learning (ML) models with large-scale outpatient data predict asthma exacerbations?Study Design and Methods: We analyzed data extracted from electronic health records (EHRs) of asthma patients treated at the Cleveland Clinic from 2010 through 2018. Demographic information, comorbidities, laboratory values, and asthma medications were included as covariates. Three different models were built with logistic regression, random forests, and a gradient boosting decision tree to predict: (1) nonsevere asthma exacerbation requiring oral glucocorticoid burst, (2) ED visits, and (3) hospitalizations.Results: Of 60,302 patients, 19,772 (32.8%) had at least one nonsevere exacerbation requiring oral glucocorticoid burst, 1,748 (2.9%) requiring and ED visit and 902 (1.5%) requiring hospitalization. Nonsevere exacerbation, ED visit, and hospitalization were predicted best by light gradient boosting machine, an algorithm used in ML to fit predictive analytic models, and had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.70-0.72), 0.88 (95% CI, 0.86-0.89), and 0.85 (95% CI, 0.82-0.88), respectively. Risk factors for all three outcomes included age, long-acting β agonist, high-dose inhaled glucocorticoid, or chronic oral glucocorticoid therapy. In subgroup analysis of 9,448 patients with spirometry data, low FEV1 and FEV1 to FVC ratio were identified as top risk factors for asthma exacerbation, ED visits, and hospitalization. However, adding pulmonary function tests did not improve models' prediction performance.Interpretation: Models built with an ML algorithm from real-world outpatient EHR data accurately predicted asthma exacerbation and can be incorporated into clinical decision tools to enhance outpatient care and to prevent adverse outcomes. [ABSTRACT FROM AUTHOR]

Patients with advanced chronic obstructive pulmonary disease (COPD) develop skeletal muscle loss (sarcopenia) that is associated with adverse clinical outcomes including mortality. We evaluated if thoracic muscle area is associated with clinical outcomes in patients with severe COPD. We analyzed consecutive patients with severe COPD undergoing evaluation for lung volume reduction from 2015 to 2019 (n = 117) compared to current and former smoking controls undergoing lung cancer screening with normal lung function (n = 41). Quantitative assessments of pectoralis muscle (PM) and erector spinae muscle (ESM) cross sectional area (CSA) were related to clinical outcomes including composite endpoints. Our results showed a reduction in PM CSA but not ESM CSA was associated with the severity of GOLD stage of COPD. Current smokers demonstrated reduced PM CSA which was similar to that in COPD patients who were GOLD stages 3 and 4. PM CSA was associated positively with FEV1, FEV1% predicted, FVC, DLCO, and FEV1/FVC ratio, and was associated negatively with the degree of radiologic emphysema. ESM correlated positively with DLCO, RV/TLC (a marker of hyperinflation), and correlated negatively with radiologic severity of emphysema. Kaplan-Meier analysis showed that reductions in PM but not ESM CSA was associated with the composite end point of mortality, need for lung volume reduction, or lung transplant. In conclusion, in well-characterized patients with severe COPD referred for lung volume reduction, PM CSA correlated with severity of lung disease, mortality, and need for advanced therapies. In addition to predicting clinical outcomes, targeting sarcopenia is a potential therapeutic approach in patients with severe COPD. [ABSTRACT FROM AUTHOR]

Background and objective: COPD is the third most common cause of death worldwide and fourth most common in the United States. In hospitalized patients with COPD, mortality, morbidity and healthcare resource utilization are high. Skeletal muscle loss is frequent in patients with COPD. However, the impact of muscle loss on adverse outcomes has not been systematically evaluated. We tested the hypothesis that patients hospitalized for COPD exacerbation with, compared to those without, a secondary diagnosis of muscle loss phenotype (all ICD‐9 codes associated with muscle loss including cachexia) will have higher mortality and cost of care. Methods: The NIS database of hospitalized patients in 2011 (1 January–31 December) in the United States was used. The impact of a muscle loss phenotype on in‐hospital mortality, LOS and cost of care for each of the 174 808 hospitalizations for COPD exacerbations was analysed. Results: Of the subjects admitted for a COPD exacerbation, 12 977 (7.4%) had a secondary diagnosis of muscle loss phenotype. A diagnosis of muscle loss phenotype was associated with significantly higher in‐hospital mortality (14.6% vs 5.7%, P < 0.001), LOS (13.3 + 17.1 vs 5.7 + 7.6, P < 0.001) and median hospital charge per patient ($13 947 vs $6610, P < 0.001). Multivariate regression analysis showed that muscle loss phenotype increased mortality by 111% (95% CI: 2.0–2.2, P < 0.001), LOS by 68.4% (P < 0.001) and the direct cost of care by 83.7% (P < 0.001) compared to those without muscle loss. Conclusion: In‐hospital mortality, LOS and healthcare costs are higher in patients with COPD exacerbations and a muscle loss phenotype. Using a large national data set of patients admitted for a COPD exacerbation with and without muscle loss phenotype, we showed that mortality, LOS and cost are considerably higher in patients with muscle loss phenotype. We demonstrated the need for targeted interventions to improve outcomes for patients with COPD. See relatedEditorial [ABSTRACT FROM AUTHOR]

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-hydroxymethylbutyrate 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. [ABSTRACT FROM AUTHOR]

Introduction: The effect of electronic inhaler monitoring (EIM) on healthcare utilization in chronic obstructive pulmonary disease (COPD) has not been studied. We hypothesized that the use of EIM in conjunction with a disease management program reduces healthcare utilization in patients with COPD.Methods: This is a retrospective pre- and post-analysis of a quality improvement project. Patients with COPD and high healthcare utilization (≥one hospitalization or emergency room visit during the year prior to enrolment) were provided with electronic monitoring devices for monitoring controller and rescue inhaler utilization for one year. Patients were contacted when alerts were triggered, indicating suboptimal adherence to controller inhaler or increased use of rescue inhalers, potentially signalling an impending exacerbation. Healthcare utilization was assessed pre- and post-monitoring, with each subject serving as his/her own control.Results: Patients with COPD and high healthcare utilization (n = 39) were recruited. Mean EIM duration was 280.5 (±120.6) days. The mean age was 68.6 (±9.9) years, FEV1 (mean forced expiratory volume in one second) was 1.1 (±0.4) L, and mean Charlson Comorbidity index was 5.6 (±2.7). Average adherence was 44.4% (28.4%). Compared with the year prior to enrolment, EIM was associated with a reduction in COPD-related healthcare utilization per year (2.2 (±2.3) versus 3.4 (±3.2), p = 0.01). Although there was a reduction in all-cause healthcare utilization, this was not statistically significant (3.4 (±2.6) versus 4.7 (±4.1), p = 0.06).Discussion: EIM in conjunction with a disease management program may play a role in reducing healthcare utilization in COPD patients with a history of high healthcare utilization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]