There is now ample evidence from the preclinical and clinical fields that early life trauma has both dramatic and long-lasting effects on neurobiological systems and functions that are involved in ...different forms of psychopathology as well as on health in general. To date, a comprehensive review of the recent research on the effects of early and later life trauma is lacking. This book fills an obvious gap in academic and clinical literature by providing reviews which summarize and synthesize these findings. Topics considered and discussed include the possible biological and neuropsychological effects of trauma at different epochs and their effect on health. This book will be essential reading for psychiatrists, clinical psychologists, mental health professionals, social workers, pediatricians and specialists in child development.
This survey paper examines selected issues related to the intersection of three broad scholarly areas: numeracy, adult education, and vulnerability. Numeracy encompasses the ways in which people cope ...with the mathematical, quantitative, and statistical demands of adult life, and is viewed as an important outcome of schooling and as a foundational skill for all adults. The focus on vulnerability stems from the realization that concerns of policy makers and educators alike often center on populations seen as vulnerable. The paper is organized in five sections. After a brief introduction, Section 2 examines adult numeracy, focusing on five numeracy domains (health, financial, digital, civic, and workplace numeracy), literacy-numeracy linkages, functional and critical aspects of numeracy, and the centrality of numeracy practices, and notes sources of vulnerability for each of these. Section 3 sketches formal, non-formal and informal contexts in which adults learn or develop their numeracy, and examines factors that may be potential sources of vulnerability, including systemic factors and dispositional and affect factors. Section 4 reflects more broadly on the concept of vulnerability, introduces selected aspects of the papers published in this issue of ZDM Mathematics Education, and points to findings regarding adult learners who may be deemed vulnerable. The closing section summarizes conclusions and research directions regarding the intersection of the three core domains. Overall, the paper points to emerging research needs and educational challenges that are relevant to scholars, practitioners, and policy makers interested in developing the numeracy of adults as well as in the mathematics education of younger learners. Author abstract
Adult learning matters. There is now widespread agreement that modern countries depend on the creativity, skills and knowledge of the entire population for their prosperity. Many people talk of our ...future well-being in terms of a 'knowledge economy' or a 'learning society' in which every person's ability to develop new capabilities will provide them with resources that will help them and the wider community to adapt and thrive. While in theory this makes lifelong learning into an exciting prospect, in practice this broad agenda is often reduced to a narrowly economic conception.
This book reports on one of the largest research projects into lifelong learning conducted in recent years. Through over 500 in-depth interviews with a cohort of about 120 adults who were followed for three years, the Learning Lives project has built up a detailed understanding of what learning means and does in the lives of adults. The project has generated insights in how learning has changed over time and across generations, what the connections are with the changing world of work, what differences learning makes for life chances, how we can learn from life and for life, and how people's prospects of learning can be improved. Combining life history and life-course research with analysis of longitudinal survey data, this book provides important insights into the learning biographies and trajectories of adults.
The book shows that learning means and does much more in people's lives than is often acknowledged by current education policy and politics. In doing so, it is an invaluable resource for anyone with an interest in the role and potential of learning through the lifecourse.
Abstract First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer ...susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (< 20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD.
Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by neutrophilia and NLRP3 inflammasome and macrophage activation. We investigated the role of neutrophil ...extracellular traps (NETs) in the pathogenesis of AOSD, and explored the effect of NETs on activating NLRP3 inflammasome and proinflammatory macrophages.
The sera of 73 AOSD patients and 40 healthy controls were used to detect the level of cell-free DNA and NET-DNA complexes. NET formation ex vivo was analyzed using immunofluorescence and flow plates. The activation of NLRP3 inflammasome in THP-1 cells and proinflammatory macrophages stimulated with DNA purified from NETs was measured using RT-PCR, ELISA, Western blotting and flow cytometry.
The levels of cell-free DNA and NET-DNA complexes were significantly increased in the circulation of patients with AOSD compared with healthy controls, and freshly isolated neutrophils from patients with AOSD were predisposed to high levels of spontaneous NET release. Interestingly, enhanced NET release was abrogated with NADPH oxidase inhibitors and a mitochondrial scavenger. Furthermore, DNA purified from AOSD NETs activated NLRP3 inflammasomes. NET DNA from AOSD also exerted a potent capacity to accelerate the activation of CD68
CD86
macrophages and increased the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Finally, the copy number of mitochondrial DNA (mtDNA) in NETs and plasma was significantly increased in AOSD patients, suggesting that mtDNA may be involved in the activation of NLRP3 and inflammatory macrophages.
These findings implicate accelerated NET formation in AOSD pathogenesis through activation of NLRP3 and proinflammatory macrophages, and identify a novel link between neutrophils and macrophages by NET formation in AOSD.
Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The ...epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings.
To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph.
We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available.
Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS.
ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.
Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its ...genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.
We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (
= 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (
= 2,454 vs. 968) and type 2 diabetes (
= 2,779 vs. 10,396).
The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring
, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.
Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
Although psychiatric problems are less prevalent in old age within the general population, it is largely unknown whether this extends to individuals with autism spectrum disorders (ASD). We examined ...psychiatric symptoms and disorders in young, middle-aged, and older adults with and without ASD (N
max
= 344, age 19–79 years, IQ > 80). Albeit comparable to other psychiatric patients, levels of symptoms and psychological distress were high over the adult lifespan; 79 % met criteria for a psychiatric disorder at least once in their lives. Depression and anxiety were most common. However, older adults less often met criteria for any psychiatric diagnosis and, specifically, social phobia than younger adults. Hence, despite marked psychological distress, psychiatric problems are also less prevalent in older aged individuals with ASD.
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