Should aspirin be replaced with ADP blockers or anti-GPVI to manage thrombosis?

Platelets have a pivotal role in maintaining cardiovascular homeostasis. They are kept docile by endothelial derived mediators. Aberration in haemostatic balance predisposes an individual to an elevated risk of a pro-thrombotic environment. Anti-platelet therapy has been a key component to reduce this risk. However, understanding how these medications affect the balance between activation and inhibition of platelets is critical. There is now evidence that a key antiplatelet therapy – aspirin, may not be the most efficacious medicine of choice, as it can compromise both platelet inhibition and activation pathways. In this review the rationale of aspirin as an anti-thrombotic drug has been critically discussed. This review looks at how recent published trials are asking key questions on the efficacy and safety of aspirin in countering cardiovascular diseases. There is an increasing portfolio of evidence that identifies that although aspirin is a very cheap and accessible drug, it may be used in a manner that is not always beneficial to a patient, and a more nuanced and targeted use of aspirin may increase its clinical benefit and maximize patient response. The questions around the use of aspirin raises the potential for changes in its clinical use for dual anti-platelet therapy. This highlights the need to ensure that treatment is targeted in the most effective manner, and that other anti-platelet therapies may well be more efficacious and beneficial for CVD patients in their standard and personalized approaches

Effect of Hump Configurations of Porous Square Cavity on Free Convection Heat Transfer

Free convection is widely used in engineering applications, including solar energy, electronic devices, nuclear energy, and heat exchangers. A computational simulation utilizing Ansys Fluent-CFD was employed to examine the natural convection heat transfer inside a square cavity filled with pure water and saturated metal foam as a porous medium (porosity ɛ =0.9). The enclosure's lower wavy wall exhibits a high temperature (Th), while the side and upper walls have a low temperature (Tc). For different Rayleigh numbers, the study examines hump configuration and the bottom wall hump number (N). The predominant design of heat transmission was improved using the circular hump design parameters of ɛ=0.9, N=4 and Tc= 25C˚ for different Ra. This resulted in significant improvements in heat transfer enhancement and energy enhancement which were enhanced by 1.13 times, for both. The authenticity research included determining the optimal design for the square enclosure. This involved estimating the effects of hump configure and number of humps for bottom wall of enclosure. These parameters have not been studied yet. The optimum case showed the highest heat transfer coefficient (h) at circular hump, N=4 and Ra = 30´103. While the standard case had N=0 and Ra = 5´103. The CFD simulation results indicate that the primary objective of the study was achieved through the optimal design, which resulted in a significant enhancement of hydrothermal performance for both heat transfer enhancement and energy enhancement 1.13 times compared to standard case

Evaluation of a general practice based Hepatitis C virus screening intervention

In 2003 an estimated 37,500 of Scotland's population was chronically infected with HCV; 44% were undiagnosed former injecting drug users (IDU) - a priority group for arrival therapy. Aims to evaluate a hepatitis C virus (HCV) screening intervention. Outcomes measures among two similar general practice populations in an area of high HCV and drug use prevalence, one of which was exposed to an HCV screening intervention, were compared. Thirty to fifty four year old attendees of the intervention practice were opportunistically offered testing and counselling, where clinically appropriate, (November 2003 - April 2004). Outcomes: HCV test uptake, case detection, referral and treatment administration rates. Of 584 eligible attendees, 421 (72%) were offered and 117 (28%) accepted testing in the intervention practice; no testing was undertaken in the comparison practice. Prevalences of HCV antibody were 13% (15/117), 75% (3/4) and 91% (10/11) among all tested persons, current IDUs and former IDUs respectively. For 4/15 (27%) evidence of binge drinking following the receipt of their positive result, was available. Of the 11 referred to specialist care because they were HCV RNA positive, nine attended at least one appointment. Two received treatment: one had achieved a sustained viral response as of February 2008. While non targeted HCV screening in the general practice setting can detect infected former IDU, the low diagnostic yield among non IDUs limited the effectiveness of the intervention. A more targeted approach for identifying former IDUs is recommended. Additionally, the low uptake of treatment among chronically infected persons four years after diagnosis demonstrates the difficulties in clinically managing such individuals. Strategies, including support for those with a history of problem alcohol use, to improve treatment uptake are required

Bosonic D-branes at finite temperature with an external field

Bosonic boundary states at finite temperature are constructed as solutions of boundary conditions at $T\neq 0$ for bosonic open strings with a constant gauge field $F_{ab}$ coupled to the boundary. The construction is done in the framework of thermo field dynamics where a thermal Bogoliubov transformation maps states and operators to finite temperature. Boundary states are given in terms of states from the direct product space between the Fock space of the closed string and another identical copy of it. By analogy with zero temperature, the boundary states heve the interpretation of $Dp$-brane at finite temperature. The boundary conditions admit two different solutions. The entropy of the closed string in a $Dp$-brane state is computed and analysed. It is interpreted as the entropy of the $Dp$-brane at finite temperature.Comment: 21 pages, Latex, revised version with minor corrections and references added, to be published in Phys. Rev.

Platelet zinc status regulates prostaglandin-induced signaling, altering thrombus formation

Background: Approximately 17.3% of the global population exhibits an element of zinc (Zn2+) deficiency. One symptom of Zn2+ deficiency is increased bleeding through impaired hemostasis. Platelets are crucial to hemostasis and are inhibited by endothelial-derived prostacyclin (prostaglandin I2 [PGI2]), which signals via adenylyl cyclase (AC) and cyclic adenosine monophosphate signaling. In other cell types, Zn2+ modulates cyclic adenosine monophosphate concentrations by changing AC and/or phosphodiesterase activity. Objectives: To investigate if Zn2+ can modulate platelet PGI2 signaling. Methods: Platelet aggregation, spreading, and western blotting assays with Zn2+ chelators and cyclic nucleotide elevating agents were performed in washed platelets and platelet-rich plasma conditions. In vitro thrombus formation with various Zn2+ chelators and PGI2 was assessed in whole blood. Results: Incubation of whole blood or washed platelets with Zn2+ chelators caused either embolization of preformed thrombi or reversal of platelet spreading, respectively. To understand this effect, we analyzed resting platelets and identified that incubation with Zn2+ chelators elevated pVASPser157, a marker of PGI2 signaling. In agreement that Zn2+ affects PGI2 signaling, addition of the AC inhibitor SQ22536 blocked Zn2+ chelation–induced platelet spreading reversal, while addition of Zn2+ blocked PGI2-mediated platelet reversal. Moreover, Zn2+ specifically blocked forskolin-mediated AC reversal of platelet spreading. Finally, PGI2 inhibition of platelet aggregation and in vitro thrombus formation was potentiated in the presence of low doses of Zn2+ chelators, increasing its effectiveness in inducing platelet inhibition. Conclusion: Zn2+ chelation potentiates platelet PGI2 signaling, elevating PGI2’s ability to prevent effective platelet activation, aggregation, and thrombus formation

Green nanosilicas for monoaromatic hydrocarbons removal from air

We demonstrate a novel application of green nanosilicas (GN), prepared via an environmentally friendly route, in removing volatile organic compounds (VOCs). Herein, we aim to establish GN as viable alternatives to traditional mesoporous silicas for the removal of monoaromatic hydrocarbons (MAHC). The results show that the GN have high extraction efficiencies comparable to those previously reported for mesoporous silicas. It was demonstrated that bespoke GN can be syntheised readily with the ability to tailor their physical properties and MAHC adsorption. In order to understand the MAHC adsorption by GN, their porosity, morphology and pore structure were characterised. It was observed that the combination of broad pore size distribution and, in particular, the presence of meso- and micro-porosity in GN contributed to high MAHC extraction efficiencies and selectivity. Although from a commercial viewpoint, further optimisation of GN is desirable in order to replace traditional sorbents, this work clearly highlights a new family of “green” sorbents, which can be prepared with a substantial reduction in secondary pollution with potential applications in selective gas separation

Seasonal, episodic and periodic changes in terrestrial water storage recorded By DEEP Piezometric Monitoring in the Ganges/Brahmaputra/Meghna DELTA

Piezometric monitoring in vertical profile at sites across the southern and coastal floodplains of the Ganges/Brahmaputra/Meghna (GBM) delta confirms gravitational flow in sediments of the Bengal Aquifer System (BAS) to a depth of at least 320 m (the maximum depth of measurement). Individual and paired records of groundwater head indicate seasonal recovery and recession of water storage, periodic and episodic ground surface loading, and earth tide responses. Lunar periodicity in groundwater head fluctuation coincident with tide height at one coastal site is consistent with tidal surface loading/unloading. Diurnal tidal fluctuations in the same record change amplitude and shift phase with depth, also indicative of surface loading/unloading. Transience in the surface loading signals with depth is governed by the vertically integrated hydraulic properties of the thick BAS sedimentary sequence. Inland, earth tide responses of smaller amplitude and lacking phase shift with depth are ubiquitous in the background signal. Most records include clearly resolvable episodic deflections in the order of 0.1 m water head and up to 0.5 m water head, near simultaneous with depth, corresponding to individual episodes of rainfall. The episodic head deflections provide a record of change in terrestrial water storage (ΔTWS) comprising undifferentiated surface water flooding, soil moisture and shallow groundwater recharge – a direct land-based equivalent of satellite estimates of ΔTWS. Enigmatic short-term recession from individual deflection peaks may be related to elastic deformation and ground surface lowering under terrestrial water storage loading

Cross-over behaviour in a communication network

We address the problem of message transfer in a communication network. The network consists of nodes and links, with the nodes lying on a two dimensional lattice. Each node has connections with its nearest neighbours, whereas some special nodes, which are designated as hubs, have connections to all the sites within a certain area of influence. The degree distribution for this network is bimodal in nature and has finite variance. The distribution of travel times between two sites situated at a fixed distance on this lattice shows fat fractal behaviour as a function of hub-density. If extra assortative connections are now introduced between the hubs so that each hub is connected to two or three other hubs, the distribution crosses over to power-law behaviour. Cross-over behaviour is also seen if end-to-end short cuts are introduced between hubs whose areas of influence overlap, but this is much milder in nature. In yet another information transmission process, namely, the spread of infection on the network with assortative connections, we again observed cross-over behaviour of another type, viz. from one power-law to another for the threshold values of disease transmission probability. Our results are relevant for the understanding of the role of network topology in information spread processes.Comment: 12 figure

B-->pi and B-->K transitions in standard and quenched chiral perturbation theory

We study the effects of chiral logs on the heavy-->light pseudoscalar meson transition form factors by using standard and quenched chiral perturbation theory combined with the static heavy quark limit. The resulting expressions are used to indicate the size of uncertainties due to the use of the quenched approximation in the current lattice studies. They may also be used to assess the size of systematic uncertainties induced by missing chiral log terms in extrapolating toward the physical pion mass. We also provide the coefficient multiplying the quenched chiral log, which may be useful if the quenched lattice studies are performed with very light mesons.Comment: 33 pages, 8 PostScript figures, version to appear in PR

Engineering threshold-based selection systems

Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems