Once suspected, the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is straightforward when flow cytometric analysis of the peripheral blood reveals a population of glycosyl ...phosphatidylinositol anchor protein-deficient cells. But PNH is clinically heterogeneous, with some patients having a disease process characterized by florid intravascular, complement-mediated hemolysis, whereas in others, bone marrow failure dominates the clinical picture with modest or even no evidence of hemolysis observed. The clinical heterogeneity is due to the close, though incompletely understood, relationship between PNH and immune-mediated bone marrow failure, and that PNH is an acquired, nonmalignant clonal disease of the hematopoietic stem cells. Bone marrow failure complicates management of PNH because compromised erythropoiesis contributes, to a greater or lesser degree, to the anemia; in addition, the extent to which the mutant stem cell clone expands in an individual patient determines the magnitude of the hemolytic component of the disease. An understanding of the unique pathobiology of PNH in relationship both to complement physiology and immune-mediated bone marrow failure provides the basis for a systematic approach to management.
Natural hazard events provide opportunities for policy change to enhance disaster risk reduction (DRR), yet it remains unclear whether these events actually fulfill this transformative role around ...the world. Here, we investigate relationships between the frequency (number of events) and severity (fatalities, economic losses, and affected people) of natural hazards and DRR policy change in 85 countries over eight years. Our results show that frequency and severity factors are generally unassociated with improved DRR policy when controlling for income-levels, differences in starting policy values, and hazard event types. This is a robust result that accounts for event frequency and different hazard severity indicators, four baseline periods estimating hazard impacts, and multiple policy indicators. Although we show that natural hazards are unassociated with improved DRR policy globally, the study unveils variability in policy progress between countries experiencing similar levels of hazard frequency and severity.
How Do Red Blood Cells Die? Thiagarajan, Perumal; Parker, Charles J; Prchal, Josef T
Frontiers in physiology,
03/2021, Letnik:
12
Journal Article
Recenzirano
Odprti dostop
Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages ...phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in
red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction.
Whether disasters influence adaptation actions in cities is contested. Yet, the extant knowledge base primarily consists of single or small-N case studies, so there is no global overview of the ...evidence on disaster impacts and adaptation. Here, we use regression analysis to explore the effects of disaster frequency and severity on four adaptation action types in 549 cities. In countries with greater adaptive capacity, economic losses increase city-level actions targeting recently experienced disaster event types, as well as actions to strengthen general disaster preparedness. An increase in disaster frequency reduces actions targeting hazard types other than those that recently occurred, while human losses have few effects. Comparisons between cities across levels of adaptive capacity indicate a wealth effect. More affluent countries incur greater economic damages from disasters, but also have higher governance capacity, creating both incentives and opportunities for adaptation measures. While disaster frequency and severity had a limited impact on adaptation actions overall, results are sensitive to which disaster impacts, adaptation action types, and adaptive capacities are considered.
Summary The complement system plays a central part in both innate and acquired immunity, but the contribution of complement activation to pathobiology is largely ancillary. An exception to the ...non-dominant role of complement in disease is the haemolytic anaemia of paroxysmal nocturnal haemoglobinuria (PNH). The intravascular haemolysis that is the clinical hallmark of PNH is a consequence of deficiency of the complement inhibitory proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59). Eculizumab is a humanised monoclonal antibody that binds and prevents activation of complement C5 and the subsequent formation of the cytolytic membrane attack complex of complement. Eculizumab inhibits the intravascular haemolysis of PNH, reduces transfusion requirements, stabilises haemoglobin concentration, and improves quality of life. Although chronic treatment with eculizumab increases the risk of infections with Neisseria meningitides , the drug is generally safe and well tolerated. But as is the case with other drugs developed for treatment of ultra-orphan diseases, eculizumab is expensive, and treatment must continue indefinitely because C5 inhibition does not affect the process (ie, clonal proliferation of haemopoietic stem cells with a mutant phosphatidylinositol glycan complementation class A PIGA gene) that underlies PNH. Moreover, due to the heterogeneous nature of the disease, treatment with eculizumab is not appropriate for all patients with PNH.
The role of American leadership in the UN climate negotiations that produced the 2015 Paris Agreement is examined. First, United States (US) climate goals are identified. Then, utilizing unique ...survey data collected at eight UN climate summits between 2008 and 2015, the extent to which the US was recognized as a leader by potential followers is investigated. Finally, the extent to which US goals are reflected in negotiation outcomes is evaluated. Recognition of the US as a leader varied over time, peaking at the UN climate meetings in Copenhagen and Paris, reflecting US leadership in shaping the outcomes of both meetings. Although the results reveal a divided leadership landscape in which the US must compete for leadership with other actors, such as the European Union and China, US leadership was crucial to the successful adoption of the Paris Agreement.
This article describes the design of an energy management system for a stand-alone cellular-connected outdoor trail camera that can operate without a power grid connection for a long duration. The ...primary focus of the study is to increase the operational lifetime of the system while decreasing human interference and the demand for maintenance, thereby enhancing the user experience. This is achieved by actively hybridizing three different battery types and a charging circuit supplied by a solar photovoltaic (PV) panel to harvest additional energy. This article investigates different user types and energy requirements for a hunting application. Considering the heterogeneous energy demand and cost requirements of the different user types, the battery energy storage, and PV system size are flexibly adjusted to satisfy the demand of the different types of users. While the proposed energy management circuit comes with an incremental cost increase to the trail camera, it provides essential functionality that will sustain stand-alone operation for a total five years with at most eight maintenance visits, decreasing the maintenance demand of the camera considerably.
Stretchable supercapacitors have received increasing attention due to their broad applications in developing self‐powered stretchable electronics for wearable electronics, epidermal and implantable ...electronics, and biomedical devices that are capable of sustaining large deformations and conforming to complicated surfaces. In this work, a new type of highly stretchable and reliable supercapacitor is developed based on crumpled vertically aligned carbon nanotube (CNT) forests transferred onto an elastomer substrate with the assistance of a thermal annealing process in atmosphere environment. The crumpled CNT‐forest electrodes demonstrated good electrochemical performance and stability under either uniaxial (300%) or biaxial strains (300% × 300%) for thousands of stretching–relaxing cycles. The resulting supercapacitors can sustain a stretchability of 800% and possess a specific capacitance of 5 mF cm−2 at the scan rate of 50 mV s−1. Furthermore, the crumpled CNT‐forest electrodes can be easily decorated with impregnated metal oxide nanoparticles to improve the specific capacitance and energy density of the supercapacitors. The approach developed in this work offers an alternative strategy for developing novel stretchable energy devices with vertically aligned nanotubes or nanowires for advanced applications in stretchable, flexible, and wearable electronic systems.
Stretchable electrodes based on crumpled carbon nanotube (CNT)‐forests are fabricated by harnessing the mechanical instability of vertically aligned CNT arrays transferred on an elastomer substrate. The all‐solid‐state stretchable supercapacitors assembled by these electrodes and the PVA/KCl gel electrolyte demonstrate superior performance under large strain deformations, offering a new approach and an opportunity for integrating next‐generation self‐powered flexible and stretchable electronics.
A general malaise exists today about the prospects for timely and effective climate action. This calls for increased attention to factors that enable climate policy change. Among these enabling ...factors are hydrological, climatological, and meteorological disasters, including floods, extreme temperatures, drought, wildfires, and storms. What impacts these disasters have on climate policy-making is contested; some view them as potential focusing events leading to unique opportunities for policy learning and reform, while others anticipate no or limited effects. Recent research, however, has yielded few advances to document and explain these diverging outcomes. This article revisits research on how climate disasters shape climate policy-making to identify knowledge gaps and future research directions. The article highlights past research foci as a basis for pinpointing unresolved puzzles, questions, and phenomena. Future research directions are identified, including the general association between disaster events and climate policy-making, policy design and quality, and the potential for ripple effects from different disaster types and across policy issue areas. These research directions aim to widen the perspective regarding how post-disaster politics may shape climate policy-making and the factors that matter in this process. Redirecting the focus from documenting types and patterns of policy change to identifying policy designs that lead to positive outcomes is a particularly promising avenue for advancing this research and contributing to climate policy-making.
Efforts to improve post-disaster policy learning and reform need to recognize that disasters are political events where policy actors often must respond to public criticism while at the same time identifying policy lessons.
Whether disasters enable constructive policy-making depends on how events are framed by stakeholders and in public debates, including the allocation of responsibility for failure in risk reduction, planning, preparedness, and response.
Policy change prompted by disasters may be elusive because it sometimes results from subtle learning, diffusion effects from distant events, heightened risk awareness, and only materializes over the long term.
The political atmosphere of post-disaster episodes increases the risk of maladaptation and misdirected policy reforms. Therefore, policy-making should be targeted at measures that actually reduce vulnerability and enhance disaster mitigation, preparedness, response, and recovery.
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