Ocean carbon dioxide removal (OCDR) is rapidly attracting interest, as climate change is putting ecosystems at risk and endangering human communities globally. Due to the centrality of the ocean in the global carbon cycle, augmenting the carbon sequestration capacity of the ocean could be a powerful mechanism for the removal of legacy excess emissions. However, OCDR requires careful assessment due to the unique biophysical characteristics of the ocean and its centrality in the Earth system and many social systems. Using a sociotechnical system lens, this review identifies the sets of considerations that need to be included within robust assessments for OCDR decision-making. Specifically, it lays out the state of technical assessments of OCDR approaches along with key financial concerns, social issues (including public perceptions), and the underlying ethical debates and concerns that would need to be addressed if OCDR were to be deployed as a carbon dioxide removal strategy. Expected final online publication date for the Annual Review of Marine Science, Volume 15 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Huntington disease (HD) is a progressive neurodegenerative disease that is debilitating for families worldwide. Inherited in an autosomal dominant manner, HD results from a CAG expansion in the gene encoding the huntingtin protein. This mutation leads to a host of motor, cognitive, and psychiatric symptoms that generally appear in middle age. While spiny projection neurons in the striatum are the most vulnerable cell type in HD, notable atrophy occurs throughout the brain, including the white matter; for this reason, HD is now considered to be a brain-wide disease. The clinical features, ethics, and neurobiology of HD are discussed in this chapter. The chapter also reviews the exciting approaches being employed today to advance understanding of underlying mechanisms in an effort to develop therapies that would delay the onset and slow progression of this disease.
Current design standards for steel structures in North America use a structural reliability model that employs first-order probability methods. This approach yields interpretable safety indexes and corresponding probabilities of failure, based on a log-normality assumption for the load and resistance probability distributions. In this work, the suitability of a log-normal assumption for the resistance distribution is assessed numerically by constructing approximate distributions of the ultimate limit state resistance of various welded steel connections between rectangular hollow section (RHS) members. Raw data from material surveys and experimental results are combined to produce approximate resistance distributions for RHS X-connections, under branch axial compression and for a variety of geometric scenarios. It is empirically shown that resistance distributions are often well represented by log-normal distributions, despite deviations in laboratory results. This suggests that current reliability analyses, as prescribed by first-order methods such as in CSA S408-11, are adequate for a wide range of resistance models for steel members and connections, even for moderate violations of assumptions in experimental or numerical data.
Mass timber has proven to be a sustainable alternative to steel and concrete and its use in construction has increased significantly in the last decade. With building codes relaxing height limitations, there is a need for novel connection solutions for the next generation of tall timber buildings. There is also a need to ensure that mass timber products are being used responsibly and sustainably, with deconstruction and reuse being identified as important factors in this pursuit. This paper presents and discusses a new hybrid shear connection for mass timber buildings that allows for easy construction, deconstruction, and reuse of the structural elements. The connection consists of a fully threaded steel rod embedded into a CLT panel and reinforced with a layer of epoxy-based grout. The structural performance of shear connections with varying rod diameter and steel strength-grade, grout thickness, and CLT grade is analyzed. An insight into the behaviour under quasi-static monotonic incremental loads is given based on a comprehensive experimental campaign, with a total of 84 push-out tests performed on squared CLT specimens. Experiments show that strong and stiff behaviour can be achieved and that the yield point is clearly identifiable, supporting optimum capacity design strategies. This allows for the connection to be protected from damage and therefore reusable. Observed failure modes suggest that load-carrying capacity and stiffness models, as per common wood bolted connections, can be developed. This high-performance shear connection has great potential for deconstruction and reuse and supports prefabricated hybrid CLT-based structural solutions for large-scale building construction.
Several art scholars have recently doubted the prudence of thinking about the nature of aesthetic value. The problem is that traditional thinking about aesthetic value fails to capture the specificities with which empirical art scholars must grapple. This paper diagnoses how the tradition came to think in this problematic way about aesthetic value. It then sketches an approach to aesthetic value that boosts the refractive power of the tools that scholars of the arts can use to bring into focus some of the specificities they care about. The path to that goal skirts the troublesome features of traditional approaches.
In classical Hodgkin lymphoma (cHL), the highly abundant CD4+ T cells in the vicinity of tumor cells are considered essential for tumor cell survival, but are ill-defined. Although they are activated, they consistently lack expression of activation marker CD26. In this study, we compared sorted CD4+CD26- and CD4+CD26+ T cells from cHL lymph node cell suspensions by RNA sequencing and T cell receptor variable gene segment usage analysis. This revealed that although CD4+CD26- T cells are antigen experienced, they have not clonally expanded. This may well be explained by the expression of exhaustion associated transcription factors TOX and TOX2, immune checkpoints PDCD1 and CD200, and chemokine CXCL13, which were amongst the 100 significantly enriched genes in comparison with the CD4+CD26+ T cells. Findings were validated in single-cell RNA sequencing data from an independent cohort. Interestingly, immunohistochemistry revealed predominant and high frequency of staining for TOX and TOX2 in the T cells attached to the tumor cells. In conclusion, the dominant CD4+CD26- T cell population in cHL is antigen experienced, polyclonal, and exhausted. This population is likely a main contributor to the very high response rates to immune checkpoint inhibitors in cHL.
Spare-parts surgery in traumatic amputation sources tissue from the amputated part to cover the residual amputation defect. This case describes a trauma patient requiring below-elbow amputation. Stump closure was accomplished with a pedicled fillet flap derived from the still-attached hand, avoiding donor site morbidity and maximizing stump length.
Posterior interosseous nerve injury after distal biceps repair significantly impairs hand function. For treatment, we describe an anterior interosseous nerve to posterior interosseous nerve transfer. Our technique is useful when the injury is too distal for median nerve transfer or when the zone of injury is too long for nerve graft reconstruction.
Background and objective: Triple therapy with an inhaled corticosteroid (ICS), a long-acting β2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. Methods: We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. Results: Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331-393 days) overall, but 14 days (95% CI 12-17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). Conclusion: Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.
Background Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. Methods and results Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). Conclusion Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. Clinical trial registration ClinicalTrials.gov, NCT02220582. Registered 20 August 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582 .
Self-regulated promoting practices foster students’ development of metacognition, motivation and strategic action. These underlying learning competencies improve students' academic, social, emotional and career outcomes. Although beneficial, the development of self-regulated promoting practices is challenging, particularly for teacher candidates. This article describes self-regulated learning practices and how motivational supports for teacher candidates' self-determined motivation creates contextual conditions that foster teacher candidates’ development of these practices. The article concludes with suggestions for future research.
Accelerometers measure the acceleration of the body part they are attached and allow to estimate time spent in activity levels (sedentary behaviour, light, and moderate-to-vigorous physical activity) and sleep over a 24-h period for several consecutive days. These advantages come with the challenges to analyse the large amount of data while integrating dimensions of both physical activity/sedentary behaviour and sleep domains. This commentary raises the questions of 1) how to classify sleep breaks (i.e. wake after sleep onset) during the night within the 24-h movement behaviour framework and 2) how to assess their impact on health while also accounting for night time sleep duration and time in sedentary behaviour and physical activity during the day. The authors advocate for future collaborations between researchers from the physical activity/sedentary behaviour and sleep research fields to ensure appropriate analysis and interpretation of the tremendous amount of data recorded by the newer generation accelerometers. This is the only way forward to provide meaningfully accurate evidence to inform future 24-h movement behaviour guidelines.
Background Chronic obstructive pulmonary disease (COPD) causes 3 million deaths each year, yet 38% of COPD patients continue to smoke. Despite proof of effectiveness and universal guideline recommendations, smoking cessation interventions are underused in practice. We sought to develop an infographic featuring personalized biomedical risk assessment through future lung function decline prediction (with vs without ongoing smoking) to both prompt and enhance clinician delivery of smoking cessation advice and pharmacotherapy, and augment patient motivation to quit. Methods We recruited patients with COPD and pulmonologists from a quaternary care center in Toronto, Canada. Infographic prototype content and design was based on best evidence. After face validation, the prototype was optimized through rapid-cycle design. Each cycle consisted of: (1) infographic testing in a moderated focus group and a clinician interview (recorded/transcribed) (with questionnaire completion); (2) review of transcripts for emergent/critical findings; and (3) infographic modifications to address findings (until no new critical findings emerged). We performed iterative transcript analysis after each cycle and a summative qualitative transcript analysis with quantitative (descriptive) questionnaire analysis. Results Stopping criteria were met after 4 cycles, involving 20 patients (58% male) and 4 pulmonologists (50% male). The following qualitative themes emerged: Tool content (infographic content preferences); Tool Design (infographic design preferences); Advantages of Infographic Messaging (benefits of an infographic over other approaches); Impact of Tool on Determinants of Smoking Cessation Advice Delivery (impact on barriers and enablers to delivery of smoking cessation advice in practice); and Barriers and Enablers to Quitting (impact on barriers and enablers to quitting). Patient Likert scale ratings of infographic content and format/usability were highly positive, with improvements in scores for 20/21 questions through the design process. Providers scored the infographic at 77.8% (“superior”) on the Suitability Assessment of Materials questionnaire. Conclusions We developed a user preference-based personalized biomedical risk assessment infographic to drive smoking cessation in patients with COPD. Our findings suggest that this tool could impact behavioural determinants of provider smoking-cessation advice delivery, while increasing patient quit motivation. Impacts of the tool on provider care, patient motivation to quit, and smoking cessation success should now be evaluated in real-world settings.
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