Regulation Of Effective B Cell Responses To Chronic Infection

Chronic viral infections disrupt B cell responses leading to impaired affinity maturation and delayed control of viremia. Previous studies have identified early pre-germinal center (GC) B cell attrition but the impact of chronic infections on B cell fate decisions in GCs remains poorly understood. To address this question, we used single-cell transcriptional profiling of virus-specific GC B cells during chronic viral infection to test the hypothesis that chronic viral infection disrupted GC B cell fate decisions leading to suboptimal humoral immunity. These studies revealed a critical GC checkpoint disrupted by chronic infection specifically at the point of dark zone re-entry. During chronic viral infection, virus-specific GC B cells were shunted towards terminal plasma cell (PC) or memory B cell (MB) fates at the expense of continued participation in the GC. Early GC exit was associated with decreased B cell mutational burden and antibody quality. Mechanistically, persisting antigen and inflammation independently drove facets of dysregulation, with a key role for inflammation in directing premature terminal differentiation. Thus, these studies define GC defects during chronic viral infection and identify a critical GC checkpoint that is short-circuited, preventing optimal maturation of humoral immunity

Analysing changes in disaster terminology over the last decade

Disaster researchers devote considerable attention to concept formation in an attempt to steer DRR terminology towards greater definitional coherence. Many researchers and policy makers frequently turn to UNISDR and their oft-cited terminology guide to ensure that concepts are employed consistently between agencies and research projects. An update to this guide introduced in 2017 introduced a range of new terms while removing and redefining others that featured in the 2009 edition of the guide. Taking a comparative look at the changes introduced, this paper sets out to reflect on the direction in which the conceptual landscape in the DRR field is headed. Whether the sum of the terminological updates made by the open ended intergovernmental expert working group is positive or negative will probably depend on the stakeholder group in question. For researchers in particular, some of the new definitions should be welcomed as they are more precise and allow for better discrimination. However, as yet other definitions are more ambiguous, some researchers may prefer definitions from the 2009 guide, definitions from elsewhere, or their own stipulated definitions that suit their research needs.publishedVersio

What makes an acute emergency? Temporal manifestation patterns and global health emergencies

In this article, we consider the role that onset patterns play in shaping how acute global events are taken to be, drawing on illustrative cases from the field of global health emergencies. We identify four temporal manifestation patterns that we argue display distinct political dynamics. First, an emergent onset pattern (e.g. the H1N1 health emergency), with political dynamics dominated by novelty-induced uncertainty and lack of information as well as familiar analogies. Second, an anticipatory onset pattern (e.g. the risk of a global avian flu health emergency), with a political dynamic characterised by dread of an as-of-yet unrealised high-consequence risk. Third, a cyclical onset pattern (e.g. Ebola), with a political dynamic characterised by a sense of familiarity and expectedness, unless eventual ‘unexpected’ or ‘unprecedented’ aspects manifest themselves. Lastly, a perpetual onset pattern (e.g. antimicrobial resistance), with political dynamics characterised by incrementalism and low political salience. We argue that acuteness is often associated with a departure from expected manifestation patterns, such as an escalation or other traits that make events appear unfamiliar. Whilst drawing on global health emergences in this paper, the four categories theorised here may also be used on a range of other adversities at the global or local level

Overcoming Barriers to Proactive Response in Slow-onset Disasters

Contribution paper to the United Nations Office for Disaster Risk Reduction (UNDRR) Global Assessment Report on Disaster Risk Reduction (GAR) 2019. Source at https://www.preventionweb.net/publications/view/66508. Link to the project: https://gar.unisdr.org/. Disasters differ markedly in their speed of manifestation, which in turn greatly affects how researchers as well as authorities interpret and respond to them. In theory, disasters with a gradual and creeping onset are easier to manage than sudden and unexpected ones. However, the unfortunate reality is that hazards with a slow-onset are often ignored, left smouldering in the background, while their impacts gradually build up and strengthen over time – sometimes irreversibly so – until eventually becoming critical emergencies. This is also true for disasters where forecasts provided decision makers with several days' advance notice. Enhancing the understanding of these phenomena, including why they rarely secure proactive response, is therefore central in achieving the ambitious targets set out in the Sendai Framework for Disaster Risk Reduction (SFDRR). By focusing on six traits, or lessons associated with slow-onset disasters, this background paper sets out to elaborate on the unique challenges posed by slow-onset disasters with implications for disaster risk reduction (DRR) work. This paper summarizes these traits as: Early warning technologies do not necessarily secure proactive response to slow-onset disasters due to political and practical obstacles in the way of timely action. Generic all-hazards DRR strategies, while best practice in the context of sudden-onset disasters, are generally inappropriate for the management of slow-onset disasters. Slow-onset disasters often fall outside the mandate of specialized disaster management agencies. The geographically dispersed nature of slow-onset disaster impacts reduces their perceived severity and political salience. The concept of disaster is often equated with sudden-onset disasters. The vast majority of disaster research and theory revolves around sudden-onset disasters, generally the largest and most destructive historical events. Addressing these obstacles head on as the SFDRR process matures will enable both better prescriptive policy recommendations, as well as research that is more sensitive to the different demands introduced by slow-onset disasters

Life in Anticipation of the COVID-19 Pandemic ‘Peak’:Reflecting on ‘Strategies’ for and Variations in attempts at ‘Flattening the Curve’ and Managing the Crisis

On March 11th, 2020, the World Health Organization (WHO) declared the emerging COVID-19 threat a pandemic following the global spread of the virus. As countries around the world implemented emergency measures in a concerted effort to handle the emerging pandemic, the nature and implications of the different kinds of precautionary measures adopted have remained contested. The majority of countries opted for efforts to slow the rate of infection, whilst critics have argued for stricter and milder measures, respectively. The living experience of the pandemic is inherently temporal as it is shaped by sentiments of living in anticipation of the envisioned pandemic peak(s) and aftermath, as vividly illustrated with references to the need for ‘flattening the curve’ so as to reduce the impact of the looming or creeping crisis. This paper sets out to critically discuss the notion of pandemic ‘strategies’, recognizing also that governments altered their strategic stances throughout the initial phase of the pandemic. It is likely that the aftermath of the crisis will trigger discussions of what kind of response should be considered as best practice. Thus, greater attention to the notion of ‘strategies’ in light of the COVID-19 pandemic is in order

Exploiting more robust and efficacious deep learning techniques for modeling wind power with speed

Abstract Sound analyses of the nonlinear relationship between wind speed and power generation are crucial for the advancement of wind energy optimization. As an emerging artificial intelligence technology, deep learning has received growing attention from energy researchers for its outstanding ability to provide complex mappings. However, deep neural networks involve complex configurations, making it challenging to utilize them in practice. This paper assesses and presents a number of model-control techniques, categorized as model-oriented and data-oriented, to achieve more robust and efficacious deep neural networks for applications in the nonlinear modeling of wind power with wind speed. These carefully refined models are also compared with polynomials, simple neural networks, and not optimized deep networks with annual data of an Arctic wind farm. The results show that deep networks with sufficient parameter tunings, training optimizations, and modeling exhibit superior performance and generalization, thus possessing considerable advantages in wind energy engineering

Challenges Associated with Creeping Disasters in Disaster Risk Science and Practice: Considering Disaster Onset Dynamics

In this article, we set out to reconcile a general conceptualization of disaster temporalities by drawing on the epitome example of a creeping disaster, namely famine. Our argument is driven by the recognition that slowly manifesting disaster impacts pose distinct challenges for decision makers and researchers while there is a tendency for the disaster literature to overlook the role of disaster onset dynamics. More specifically and as a starting point, we identify four key themes that merit particular attention when dealing with creeping disasters: (1) our understanding of disaster as a phenomenon; (2) measurement and operationalization; (3) early warning and response; and (4) disaster management and termination. By integrating conceptual discussions of disaster with famine scholarship—a phenomenon often excluded from mainstream disaster research—this article provides fresh perspectives on disaster science as well as a number of implications for how we think about disaster risk reduction.publishedVersio

Living through and with the global HIV/AIDS pandemic:Distinct ‘pandemic practices’ and temporalities

In this study, we expand on the newly devised sociological concept of pandemic practices that emerged during the COVID-19 outbreak by applying it to the HIV/AIDS pandemic. The analytical heuristic of pandemic practices distinguishes between four kinds of practices: (i) primary practices that encompass the public's direct response to the pandemic, (ii) responsive practices that encompass altered routines and social interactions, (iii) adaptive practices that encompass more elusive organisational and legal legacies and (iv) meta-practices that produce particular narratives about the pandemic dynamics that might lead to lasting socio-cultural behavioural changes. In this paper we probe further into the notion of meta-practices. The results show that the prolonged nature of the HIV/AIDS pandemic combined with the widespread stigmatisation of vulnerable groups has led to distinct social practices that fragment along socio-economic lines both internally in countries but also between high-income and low-income countries. As the COVID-19 pandemic becomes increasingly endemic, lessons learned from HIV/AIDS expose the dangers of similar fragmentations where parts of the population return to normal but where many others continue to suffer not only from adverse health outcomes but also social exclusion and stigmatisation. Thus, we argue that attention to pandemic practices, and how they produce and reinforce underlying socio-economic vulnerabilities would strengthen long-term pandemic responses

Bracing for turmoil: temporalities of livelihood adaptation among informal workers in Facatativá, Colombia

his study considers temporal aspects of livelihood adaptation in times of turmoil by drawing on interviews with informal street vendors in Facatativá, Colombia. By engaging a ‘time stories’ perspective, this article aims to provide a better understanding of how livelihood responses to shocks emerge from (and are constrained by) individuals’ initial and changing assumptions about the continued onset of a crisis. We found that livelihood adaptation to shock, in some cases, involves adopting a new livelihood that appears more durable. In other cases, adaptation is temporary with individuals returning to prior livelihoods when conditions allow. Many individuals had limited livelihood options. In such cases adaptation was more precarious generally, implying drastic consumption cuts or relying on neighborly networks. Also, changing one’s livelihood is a high-risk decision for people who are often already struggling to survive in a context of declining overall demand and falling incomes as a crisis hits

Life in Anticipation of Wind Power Development: Three Cases from Coastal Norway

Wind power development, whilst welcomed by many as a potentially green source of energy, also gives rise to considerable local resistance. Drawing on three case studies from coastal Norway (Frøya, Haramsøy, and Egersund), the present article sets out to reflect on life in anticipation of wind power development. Reflecting on the nature of life in anticipation of undesired wind power developments, with implications for how life is lived in dread of imminent adversities in general (such as climate change, pandemics, and disaster risks), these case studies focus on how communities relate to the future and how they perceive and strive to organise so as to shape outcomes. A central point raised in this article is that wind power projects could become more socially, environmentally and economically sustainable if greater attention is paid to working with communities to reduce distrust and uncertainties before, during and after such projects. Hence, relational work carried out that may shape the affective state of anticipation prior to and during wind farm construction can be understood as crucial to the sustainability of large-scale green infrastructure projects.publishedVersio