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Aims We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). Methods and results Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z -score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z -score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95–0.99] and 1.6 [1.2–2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. Conclusion In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM. [ABSTRACT FROM AUTHOR]

Inoculation theory, which applies the biological concept of vaccination to misinformation, provides a range of ways to effectively build resilience against misinformation. In this article, we define and organize the various types of inoculation, which includes three delivery mechanisms that can be useful in the classroom—passive, active, and experiential. In passive inoculations, students passively receive inoculating messages, whereas in active inoculations, students actively generate misinformation using misleading techniques. We introduce a new category of inoculation—experiential—which involves misleading students and then debriefing them on how they were misled. We then describe how these three techniques were implemented in a general education science class designed to teach critical thinking and science literacy. Through these activities, we illustrate how the different types of inoculation can be creatively combined to maximize student engagement and learning. [ABSTRACT FROM AUTHOR]

Misinformation about climate change is a consequential societal issue, causing polarization and reduced support for climate action. However, the seriousness of the problem does not preclude non-serious solutions. There are numerous potential benefits to humor as a strategy to counter misinformation, such as attracting attention and engaging disengaged audiences. This paper describes a humorous serious game—"Cranky Uncle"—developed in the U.S. to inoculate players against climate misinformation. The game combines psychological research into active inoculation, critical-thinking work on misleading rhetorical techniques, communication research into cartoon debunking, and gamification. The game's cartoon humor and the creative potential of active inoculation lends it to classroom applications; educators have thus used classroom activities to complement the game in order to improve students' climate literacy and critical-thinking abilities. We present several qualitative U.S.-based case studies, in formal English-speaking tertiary classrooms and informal public education settings, to illustrate the utility of a humorous, game-based approach to building resilience against climate misinformation. The approaches adopted in our case studies are offered as a model for other educators looking to use interactive games to teach critical thinking. [ABSTRACT FROM AUTHOR]

Background: Direct comparisons of paediatric hospitalizations for acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. We describe the absolute and relative hospital burden of acute paediatric COVID-19 and MIS-C in Canada. Methods: This national prospective study was conducted via the Canadian Paediatric Surveillance Program from March 2020-May 2021. Children younger than 18 years old and hospitalized for acute COVID-19 or MIS-C were included in the analysis. Outcomes included supplemental oxygen (low-flow oxygen or high-flow nasal cannula), ventilation (non-invasive or conventional mechanical), vasopressors, paediatric intensive care unit (PICU) admission, or death. Adjusted risk differences (aRD) and 95% confidence intervals (CI) were calculated to identify factors associated with each diagnosis. Results: Overall, we identified 330 children hospitalized for acute COVID-19 (including five deaths) and 208 hospitalized for MIS-C (including zero deaths); PICU admission was required for 49.5% of MIS-C hospitalizations versus 18.2% of acute COVID-19 hospitalizations (aRD 20.3; 95% CI, 9.9-30.8). Resource use differed by age, with children younger than one year hospitalized more often for acute COVID-19 (aRD 43.4% versus MIS-C; 95% CI, 37.7-49.1) and more children 5-11 years hospitalized for MIS-C (aRD 38.9% vs. acute COVID-19; 95% CI, 31.0-46.9). Conclusion: While there were more hospitalizations and deaths from acute paediatric COVID-19, MIS-C cases were more severe, requiring more intensive care and vasopressor support. Our findings suggest that both acute COVID-19 and MIS-C should be considered when assessing the overall burden of severe acute respiratory syndrome coronavirus 2 in hospitalized children. [ABSTRACT FROM AUTHOR]

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Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease. [ABSTRACT FROM AUTHOR]

Although officer proximity to a grade 2 (non-emergency) incident is the primary metric used by dispatchers to allocate officers from deployment, other (informal) factors may influence the decision. The purpose of this research was to identify additional metrics that could be used to better match officer attributes to incident characteristics. Using a form of grounded theory, interviews with dispatchers in a single constabulary were used to identify 14 additional metrics that could be used in a formal decision-making process implemented through software assistance. The metrics broadly fell into the three categories of response time, officer attributes, and incident attributes. Dispatchers generally considered the introduction of a greater range of metrics implemented as software assistance to be beneficial but considered software decision-making tools to be unacceptable. We conclude that the weighting attached to each new metric relative to others should be tailored to the constabulary and operation group with which the dispatcher works. Overall, it is considered desirable to introduce a wider range of metrics through which dispatch of officers to non-emergency incidents may be managed. [ABSTRACT FROM AUTHOR]

The 2014-2015 epidemic of Ebola virus disease in West Africa primarily affected Guinea, Liberia, and Sierra Leone. Several countries, including Mali, Nigeria, and Senegal, experienced Ebola importations. Realizing the importance of a trained field epidemiology workforce in neighboring countries to respond to Ebola importations, the Centers for Disease Control and Prevention Field Epidemiology Training Program unit implemented the Surveillance Training for Ebola Preparedness (STEP) initiative. STEP was a mentored, competency-based initiative to rapidly build up surveillance capacity along the borders of the at-risk neighboring countries Côte d'Ivoire, Mali, Senegal, and Guinea-Bissau. The target audience was district surveillance officers. STEP was delivered to 185 participants from 72 health units (districts or regions). Timeliness of reporting and the quality of surveillance analyses improved 3 months after training. STEP demonstrated that mentored, competency-based training, where learners attain competencies while delivering essential public health services, can be successfully implemented in an emergency response setting. [ABSTRACT FROM AUTHOR]

Purpose This study aims to investigate the effectiveness of a theory-driven realist evaluative research approach to better understand complex technology implementations in organizations.Design/methodology/approach An institution wide e-learning implementation of lecture capture (LC), within a UK University, was chosen, and a realist evaluation framework was used, tailored for educational technology. The research was conducted over four, increasingly focused, evaluation cycles combining engagement analytics, user interviews and theory to refine what works (or does not work), for whom, in which contexts and why.Findings Despite explicit demand and corresponding investment, overall student engagement is lower than expected. Increased student use appears linked to particular staff attitudes and behaviours and not to specific disciplines or course content. The main benefits of LC are providing reassurance to the majority, aiding revision and understanding for the many and enabling catch-up for the few. Recommendations for future research are based on some unexpected outcomes uncovered, including evolving detrimental student behaviours, policy development based on technological determinism and future learner-centred system development for next-generation LC technologies.Practical implications The realist approach taken, and evaluation framework used, can be adopted (and adapted) for future evaluative research. Domain specific reference models, categorizing people and technology, supported analysis across multiple contexts.Originality/value This study responds to a call for more theory-based research in the field of educational technology. The authors demonstrate that a theory-driven approach provides real and practical recommendations for institutions and allows for greater insight into the political, economic and social complexity of technology implementation. [ABSTRACT FROM AUTHOR]

The impact of CD4+ regulatory T cells (Tregs) on human immunodeficiency virus type 1 (HIV-1) pathogenesis remains incompletely understood. Although it has been shown that Tregs can be infected with HIV-1, the consequences of infection on a per-cell basis are still unknown. In vitro HIV-GFP infected and noninfected Tregs were isolated by flow-based cell-sorting to investigate Treg suppressive capacity and gene expression profiles. Our data show that HIV-1-infected Tregs were significantly less suppressive than noninfected Tregs and demonstrated down-regulation of genes critical to Treg function. This impaired function may have detrimental consequences for the control of generalized immune activation and accelerate HIV disease progression. [ABSTRACT FROM AUTHOR]

While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable formof stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1.Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to shamlevels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1–infected individuals and HIV-1 negative controls. While HIV “elite controllers” and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors. [ABSTRACT FROM PUBLISHER]

The last couple of years have brought a rise in the number of institutional repositories throughout the world and within UK Higher Education institutions, with the majority of these repositories being devoted to research output. Repositories containing teaching and learning material are less common and the workflows and business processes surrounding these types of repositories were unclear. The user motivations to contributing to and downloading from repositories were also unknown. This article reports on two studies: a wide- scale survey carried out with HE staff to identify barriers and incentives to contributing to teaching material repositories; and inter- views carried out as part of a workflow study at Loughborough University, to identify existing practice in the creation and sharing of teaching material. Confusion is reported with regard to the difference between a Virtual Learning Environment (VLE) and a repository. However, many different purposes of a teaching and learning material repository are highlighted. This article discusses how repositories could successfully interoperate with other institutional applications and highlights the benefits of teaching material repositories to the user, through scenarios. Recommendations relating to the key aspects of the design and implementation of a repository service are outlined. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

A letter to the editor and a reply are presented in response to the article "New therapeutic products and difficult decisions: The case of recombinant factor VIII in the management of haemophilia A" in the 1998 issue.

Monoamine and amino acid content were measured in brain regions from 12 week old male, homozygous Brattleboro (DI, n=12) and Long-Evans control (LE, n=12) rats. Norepinephrine (NE) content was significantly elevated (16-25%) in the spinal cord, pons-medulla and anterior hypothalamus of DI rats when compared to LE controls. NE content of the neurointermediate lobe of pituitary in DI rats was almost twice that of LE controls. Serotonin content was also significantly elevated in the spinal cord, pons-medulla, anterior hypothalamus and forebrain of DI rats relative to the LE controls. Taurine content in DI rats was increased (31-42%) above that of LE rats in the anterior hypothalamus, striatum and forebrain. Glutamine content was also greater in DI rats than LE in the spinal cord, pons-medulla, anterior hypothalamus, striatum, hippocampus and forebrain. The changes in monoamine and amino acid content were discussed in relation to the cardiovascular and osmoregulatory deficits that are present in DI rats due to arginine vasopressin (AVP) deficiency. The possible role of AVP in modulating NE turnover was also discussed. The increase in brain TAU content in DI rats may be a physiological response to hypernatremia. [ABSTRACT FROM AUTHOR]

The 2014-2015 epidemic of Ebola virus disease in West Africa primarily affected Guinea, Liberia, and Sierra Leone. Several countries, including Mali, Nigeria, and Senegal, experienced Ebola importations. Realizing the importance of a trained field epidemiology workforce in neighboring countries to respond to Ebola importations, the Centers for Disease Control and Prevention Field Epidemiology Training Program unit implemented the Surveillance Training for Ebola Preparedness (STEP) initiative. STEP was a mentored, competency-based initiative to rapidly build up surveillance capacity along the borders of the at-risk neighboring countries Côte d'Ivoire, Mali, Senegal, and Guinea-Bissau. The target audience was district surveillance officers. STEP was delivered to 185 participants from 72 health units (districts or regions). Timeliness of reporting and the quality of surveillance analyses improved 3 months after training. STEP demonstrated that mentored, competency-based training, where learners attain competencies while delivering essential public health services, can be successfully implemented in an emergency response setting. [ABSTRACT FROM AUTHOR]

A letter to the editor and a reply are presented in response to the article "Body mass index: a comparison between self-reported and measured height and weight" in the 1988 issue.