Atrial fibrillation in sub-saharan Africa: epidemiology, unmet needs, and treatment options

Health care in Sub-Saharan Africa is being challenged by a double burden of disease as lifestyle diseases common in the developed world, such as stroke and atrial fibrillation (AF), increase, while, simultaneously, health issues of the developing world in terms of communicable disease persist. The prevalence of AF is lower in Africa than in the developed world but is expected to increase significantly over the next few decades. Patients with AF in Africa tend to be younger and have a higher prevalence of rheumatic valvular heart disease than patients with AF in other regions. Permanent AF is the most prevalent type of AF in Africa, possibly due to the lower use of rhythm control strategies than in the developed world. Mortality rates of patients with AF in Africa are high, due largely to poor health care access and suboptimal therapy. The risk of stroke in AF, which is moderate to high in Africans as in the developed world, contributes to the high mortality rate. Patients with AF in Africa are often undertreated with antithrombotics, as cost and access to monitoring are major barriers. Vitamin K antagonists, including warfarin, are the most commonly available oral anticoagulants, but regular monitoring can be challenging, especially for patients in remote areas. Several non-vitamin K antagonist oral anticoagulants (NOACs) have been approved for use in countries across Sub-Saharan Africa and have the potential to reduce stroke burden. The higher cost of newer agents may be offset by the reduced need for regular monitoring, fixed dosing, and lower risk of intracranial bleeding; NOACs could provide a treatment option for patients in remote areas with limited access to regular monitoring. However, NOACs are not indicated in valvular AF. More work is needed to increase understanding of the epidemiology of AF and stroke, as well as to improve management strategies to reduce the burden of cardiovascular disease predicted for Africa

Duration of heart failure and the risk of atrial fibrillation: different mechanisms at different times?

Chronic heart failure increases the risk of atrial fibrillation (AF), with the prevalence of AF paralleling the severity of heart failure.1 Factors that underlie this increased susceptibility to AF may include electrical, structural, and neurohumoral changes.2 In AF, it is recognized that atrial electrophysiological remodelling occurs and contributes to the perpetuation of the arrhythmia, most notably the decrease of effective refractory period (ERP) which predisposes to re-entry by shortening the wavelength. Does heart failure cause similar changes in atrial electrophysiology that predispose to the arrhythmia

Nitrogen and phosphorus limitation of oceanic microbial growth during spring in the Gulf of Aqaba

Bioassay experiments were performed to identify how growth of key groups within the microbial community was simultaneously limited by nutrient (nitrogen and phosphorus) availability during spring in the Gulf of Aqaba's oceanic waters. Measurements of chlorophyll a (chl a) concentration and fast repetition rate (FRR) fluorescence generally demonstrated that growth of obligate phototrophic phytoplankton was co-limited by N and P and growth of facultative aerobic anoxygenic photoheterotropic (AAP) bacteria was limited by N. Phytoplankton exhibited an increase in chl a biomass over 24 to 48 h upon relief of nutrient limitation. This response coincided with an increase in photosystem II (PSII) photochemical efficiency (F v /F m), but was preceded (within 24 h) by a decrease in effective absorption crosssection (σPSII) and electron turnover time (τ). A similar response for τ and bacterio-chl a was observed for the AAPs. Consistent with the up-regulation of PSII activity with FRR fluorescence were observations of newly synthesized PSII reaction centers via low temperature (77K) fluorescence spectroscopy for addition of N (and N + P). Flow cytometry revealed that the chl a and thus FRR fluorescence responses were partly driven by the picophytoplankton (æ10 μm) community, and in particular Synechococcus. Productivity of obligate heterotrophic bacteria exhibited the greatest increase in response to a natural (deep water) treatment, but only a small increase in response to N and P addition, demonstrating the importance of additional substrates (most likely dissolved organic carbon) in moderating the heterotrophs. These data support previous observations that the microbial community response (autotrophy relative to heterotrophy) is critically dependent upon the nature of transient nutrient enrichment. © Inter-Research 2009

A system in balance? ? Implications of deep vertical mixing for the nitrogen budget in the northern Red Sea, including the Gulf of Aqaba (Eilat)

International audienceWe investigated the implications of deep winter mixing for the nitrogen budget in two adjacent systems, the northern Red Sea proper, and the Gulf of Aqaba. Both are subtropical oligotrophic water bodies. The main difference is that in the gulf deep winter mixing takes place regularly, whereas the northern Red Sea proper is permanently stratified. In the Gulf of Aqaba, we observed significantly lower nitrate deficits, i.e. deviations from the Redfield ratio, than in the northern Red Sea proper. Assuming that other external inputs and losses in N or P are very similar in both systems, the higher nitrate deficit can be explained by either lower nitrogen fixation in the (stratified) northern Red Sea, which seems unlikely. An alternative explanation would be higher rates of benthic denitrification than in the gulf. By comparing the two systems we have indirect evidence that benthic denitrification was much lower in the Gulf of Aqaba due to higher oxygen concentrations. This we attributed to the occurrence of deep winter mixing, and as a consequence, the nitrate deficit was close to zero (i.e. N:P ratio close to "Redfield"). If both nitrogen fixation and benthic denitrification take place, as in the northern Red Sea proper, the result was a positive nitrate deficit (i.e. a deficit in nitrate) in the ambient water. The nitrate deficit in the northern Red Sea was observed in spite of high iron deposition from the surrounding desert. Our results strongly support the concept of nitrogen as the proximate, and phosphate as the ultimate limiting nutrient for primary production in the sea. This must not be neglected in efforts for protecting the adjacent reefs against eutrophication

Ground-Laboratory to In-Space Atomic Oxygen Correlation for the Polymer Erosion and Contamination Experiment (PEACE) Polymers

The Materials International Space Station Experiment 2 (MISSE 2) Polymer Erosion and Contamination Experiment (PEACE) polymers were exposed to the environment of low Earth orbit (LEO) for 3.95 years from 2001 to 2005. There were 41 different PEACE polymers, which were flown on the exterior of the International Space Station (ISS) in order to determine their atomic oxygen erosion yields. In LEO, atomic oxygen is an environmental durability threat, particularly for long duration mission exposures. Although spaceflight experiments, such as the MISSE 2 PEACE experiment, are ideal for determining LEO environmental durability of spacecraft materials, ground-laboratory testing is often relied upon for durability evaluation and prediction. Unfortunately, significant differences exist between LEO atomic oxygen exposure and atomic oxygen exposure in ground-laboratory facilities. These differences include variations in species, energies, thermal exposures and radiation exposures, all of which may result in different reactions and erosion rates. In an effort to improve the accuracy of ground-based durability testing, ground-laboratory to in-space atomic oxygen correlation experiments have been conducted. In these tests, the atomic oxygen erosion yields of the PEACE polymers were determined relative to Kapton H using a radio-frequency (RF) plasma asher (operated on air). The asher erosion yields were compared to the MISSE 2 PEACE erosion yields to determine the correlation between erosion rates in the two environments. This paper provides a summary of the MISSE 2 PEACE experiment; it reviews the specific polymers tested as well as the techniques used to determine erosion yield in the asher, and it provides a correlation between the space and ground laboratory erosion yield values. Using the PEACE polymers asher to in-space erosion yield ratios will allow more accurate in-space materials performance predictions to be made based on plasma asher durability evaluation

Exponential distribution of long heart beat intervals during atrial fibrillation and their relevance for white noise behaviour in power spectrum

The statistical properties of heart beat intervals of 130 long-term surface electrocardiogram recordings during atrial fibrillation (AF) are investigated. We find that the distribution of interbeat intervals exhibits a characteristic exponential tail, which is absent during sinus rhythm, as tested in a corresponding control study with 72 healthy persons. The rate of the exponential decay lies in the range 3-12 Hz and shows diurnal variations. It equals, up to statistical uncertainties, the level of the previously uncovered white noise part in the power spectrum, which is also characteristic for AF. The overall statistical features can be described by decomposing the intervals into two statistically independent times, where the first one is associated with a correlated process with 1/f noise characteristics, while the second one belongs to an uncorrelated process and is responsible for the exponential tail. It is suggested to use the rate of the exponential decay as a further parameter for a better classification of AF and for the medical diagnosis. The relevance of the findings with respect to a general understanding of AF is pointed out

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

The Archaeology of Heroes:Carlyle, Foucault and the Pedagogy of Interdisciplinary Narrative Discourse

This paper argues in favour of the beneficial currency of Thomas Carlyle's ‘On Heroes, Hero‐worship and the Heroic in History’ in three ways, each of which finds the basis of its critique in aspects of Foucault's theories of discursive practice, as explored in Foucault's theories of historical discourse; 1) that Carlyle's terminology connects with his discursive practice in an ambiguous manner, as his concept of worship is more akin to study than devotion, if we take the text of his lectures as evidence of his perception; 2) the sources of enlightenment Carlyle offers us, based on these studies of heroic individuals, may provide an exemplar for interdisciplinary scholarship centred around biographies of notable individuals, and finally; 3) we challenge the notion that heroes such as those Carlyle offers us can be manifest in the present and argue that the depth of insight Carlyle demonstrates into his subjects is only possible by means of a lengthy temporal transition: the historicity of these narratives, and the narratives of social codification, cultural development and long‐term impact witnessed and described over generations, is what makes them feasible at all

Weighted Secret Sharing from Wiretap Channels

Secret-sharing allows splitting a piece of secret information among a group of shareholders, so that it takes a large enough subset of them to recover it. In weighted secret-sharing, each shareholder has an integer weight, and it takes a subset of large-enough weight to recover the secret. Schemes in the literature for weighted threshold secret sharing either have share sizes that grow linearly with the total weight, or ones that depend on huge public information (essentially a garbled circuit) of size (quasi)polynomial in the number of parties. To do better, we investigate a relaxation, (?, ?)-ramp weighted secret sharing, where subsets of weight ? W can recover the secret (with W the total weight), but subsets of weight ? W or less cannot learn anything about it. These can be constructed from standard secret-sharing schemes, but known constructions require long shares even for short secrets, achieving share sizes of max(W,|secret|/?), where ? = ?-?. In this note we first observe that simple rounding let us replace the total weight W by N/?, where N is the number of parties. Combined with known constructions, this yields share sizes of O(max(N,|secret|)/?). Our main contribution is a novel connection between weighted secret sharing and wiretap channels, that improves or even eliminates the dependence on N, at a price of increased dependence on 1/?. We observe that for certain additive-noise (?,?) wiretap channels, any semantically secure scheme can be naturally transformed into an (?,?)-ramp weighted secret-sharing, where ?,? are essentially the respective capacities of the channels ?,?. We present two instantiations of this type of construction, one using Binary Symmetric wiretap Channels, and the other using additive Gaussian Wiretap Channels. Depending on the parameters of the underlying wiretap channels, this gives rise to (?, ?)-ramp schemes with share sizes |secret|?log N/poly(?) or even just |secret|/poly(?)

Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article