Although levodopa remains the most effective oral pharmacotherapy for Parkinson disease (PD), its use is often limited by wearing off effect and dyskinesias. Management of such complications ...continues to be a significant challenge.
To investigate the efficacy and safety of safinamide (an oral aminoamide derivative with dopaminergic and nondopaminergic actions) in levodopa-treated patients with motor fluctuations.
From March 5, 2009, through February 23, 2012, patients from academic PD care centers were randomized (1:1 ratio) to receive double-blind adjunctive safinamide or placebo for 24 weeks. All patients had idiopathic PD with "off" time (time when medication effect has worn off and parkinsonian features, including bradykinesia and rigidity, return) of greater than 1.5 hours per day (excluding morning akinesia). Their pharmacotherapy included oral levodopa plus benserazide or carbidopa in a regimen that had been stable for 4 weeks or longer. During screening, each patient's regimen was optimized to minimize motor fluctuations. Study eligibility required that after 4 weeks of optimized treatment, the patients still have more than 1.5 hours per day of off time. Adverse events caused the premature study discontinuation of 12 individuals (4.4%) in the safinamide group and 10 individuals (3.6%) in the placebo group.
Patients took safinamide or placebo as 1 tablet daily with breakfast. If no tolerability issues arose by day 14, the starting dose, 50 mg, was increased to 100 mg.
The prespecified primary outcome was each treatment group's mean change from baseline to week 24 (or last "on" treatment value) in daily "on" time (relief of parkinsonian motor features) without troublesome dyskinesia, as assessed from diary data.
At 119 centers, 549 patients were randomized (mean SD age, 61.9 9.0 years; 334 male 60.8% and 371 white 67.6%): 274 to safinamide and 275 to placebo. Among them, 245 (89.4%) receiving safinamide and 241 (87.6%) receiving placebo completed the study. Mean (SD) change in daily on time without troublesome dyskinesia was +1.42 (2.80) hours for safinamide, from a baseline of 9.30 (2.41) hours, vs +0.57 (2.47) hours for placebo, from a baseline of 9.06 (2.50) hours (least-squares mean difference, 0.96 hour; 95% CI, 0.56-1.37 hours; P < .001, analysis of covariance). The most frequently reported adverse event was dyskinesia (in 40 14.6% vs 15 5.5% and as a severe event in 5 1.8% vs 1 0.4%).
The outcomes of this trial support safinamide as an effective adjunct to levodopa in patients with PD and motor fluctuations to improve on time without troublesome dyskinesia and reduce wearing off.
clinicaltrials.gov Identifier NCT00627640.
This study reports data on the first occurrence of economic supergene Au in a near-surface silcrete horizon over the Scuddles volcanic massive sulfide (VMS) deposit in the Golden Grove district, ...Western Australia. A deep weathering profile was developed on dacite, rhyodacite, siltstone, and breccia that host primary Cu, Zn, and Pb sulfides with Au-Ag ore. From the base, the weathering profile at Scuddles is subdivided into five main zones: (1) supergene sulfide enrichment zone; (2) supergene oxide enrichment zone; (3) ferruginous saprolite; (4) leached zone of kaolinitic saprolite and silcrete; and (5) lateritic zone of mottled clays, ferruginous duricrust, and gravels. Silcrete at Scuddles hosts supergene Au deposit that formed in two generations: the first is intimately associated with Ag halides during supergene enrichment of the primary VMS, and the second is associated with kaolinite in dissolution cavities inside Ag halides during lateritic weathering. These two Au generations imply more than one mechanism of Au remobilization and formation, multiple fluid pathways, and superimposed episodes of weathering under variable timing and climatic conditions. Gold grains are pure, nanocrystalline (up to 10 nm) and clustered together forming microcrystalline aggregates. A few Au grains are residual in silcrete with Ag-Sb-rich cores and Ag-poor rims possibly formed during dealloying of Ag and Sb. Chemically, Au in silcrete is associated with a multi-element concentration of Ag, I, Br, Cl, Sb, Sn, Bi, Hg, Mo, W, Te, and Ge. Gold and Ag in the supergene weathering profile were mobilized to silcrete as a halide complex under acidic and saline conditions generated during the oxidation of massive sulfides at depth. The precipitation of Au-Ag halides in the silcrete may have taken place in response to a rise in pH. Gold was likely remobilized with kaolinite from the surface lateritic zone, facilitated by decays of plant roots and bioturbation. The clustered spongy, cube-octahedral, platy (six-sided), dendritic-, and reniform-like morphologies of Au in cavities inside Ag halides may indicate biogenic-related processes in its precipitation. Recognizing Au-Ag-rich silcrete over the buried VMS at Scuddles highlights the significance of the silcrete in finding buried VMS, particularly if the gossan is absent.
A TMDTO Attack Against Lizard Maitra, Subhamoy; Sinha, Nishant; Siddhanti, Akhilesh ...
IEEE transactions on computers,
05/2018, Letnik:
67, Številka:
5
Journal Article
Recenzirano
Lizard is a very recently proposed lightweight stream cipher that claims 60 bit security against distinguishing (related to state recovery) and 80 bit security against key recovery attack. This ...cipher has 121 bit state size. In this paper, we first note that using ψ key stream bits one can recover ψ unknown bits of the state when t state bits are fixed to a specific pattern. This is made possible by guessing the remaining state bits. We present certain values of ψ, t based on the state size that helps in mounting a generic conditional TMDTO attack following the BSW sampling. For Lizard, we obtain the preprocessing complexity as 2 67 , and the maximum of Data, Time and Memory complexity during the online phase as 2 54 . The parameters in the online phase are significantly less than 2 60 .
There is a growing trend to try to make surface geochemistry effective for exploring areas of transported cover using sensitive techniques such as partial extractions of soil and gas analysis. ...However, these techniques have had mixed success in delineating buried ore bodies, because the particular mechanisms and their effectiveness in transferring ore-related metals upwards through transported cover are poorly understood. This precludes discriminating null results (a potentially ineffective technique) from negative results (no mineralization). A review of mechanisms capable of transferring metals through barren transported cover to the surface identified those well documented and others not well studied but nonetheless promising. The mechanisms are classified according to two main processes: phreatic process involving groundwater flow, convection, dilatancy, bubbles, diffusion and electromigration; and vadose processes involving capillary migration, gaseous transport and biological transfer. Microbial metabolism affects the kinetics of many hydrochemical processes, especially sulfide oxidation and other redox transfers, and also impacts, negatively and positively, on the generation of gases throughout the entire cover sequence. Phreatic mechanisms require groundwater to transfer solutes and are most effective. These have the most predictive capability where there are shallow water tables. In the Australian landscape, groundwater occurs commonly more than 5m below surface except in lower, discharge landform sites, and therefore other mechanisms (biological, capillary, gaseous), are necessary to transfer metals up from the water table. Thus, much of the emphasis in this paper is on vadose processes. An integrated approach is necessary, combining different mechanisms with the nature and evolution of the transported cover and climatic settings. Regions and landforms of highly weathered transported cover with current or past water tables residing within the cover and long-standing vegetation will favor combined mechanisms such as electrochemical, plant uptake, capillarity, and bioturbation. Fresh, relatively unweathered and thick (>30m) transported cover may prove the most unlikely to develop surface geochemical anomalies. Gas (e.g. CO2, H2S) mechanisms may work, provided that sufficient gases are generated from the oxidation of ore to produce a surface signature.
South west Western Australia is host to some of the world's largest mineral deposits including bauxite, Ta and Au. The giant Boddington Gold Mine exploits one such deposit and is located in forested ...areas south east of Perth. Exploration for Au in this area has concentrated on sampling surficial Fe-rich lateritic residuum and its degradation products and was how Boddington was originally discovered; it has a multi-element signature. Despite its location in forest there has been little biogeochemistry undertaken in this area or consideration of whether trees (including eucalypts) are agents of dispersion of metals in this terrain. Eucalyptus trees have been shown to be responsible for forming anomalies above gold deposits in semi-arid areas of Australia and the location of Boddington in a humid environment provided an important comparison in which to investigate this possibility.
The Golden Triangle Au prospect near Boddington Gold Deposit is located on the flank of a small lateritic hill. Limited shallow drilling has identified sub-economic mineralisation with some metre composite cuttings grading >1ppm Au. A selection of different trees and shrubs, organic soil and ferruginous pisoliths were collected over a surface traverse of 800m at 50m intervals from across the prospect. Samples were analysed for major elements, Au and several pathfinder metals. Additional foliage samples were collected from the same trees over mineralisation and background to test for sample heterogeneity.
Golden Triangle vegetation samples were generally anomalous in Au and pathfinder elements (e.g. Ag, Bi, W and Sn). For example, Banksia and Macrozamia had elemental anomalies in Bi and Ag located directly above or down slope of mineralisation although for Eucalyptus the anomaly over mineralisation itself was poorly defined. Topsoil containing organic matter overlying the ferruginous pisoliths was particularly anomalous in Au (mean of 47ppb against of background of <5ppb). Pathfinder element anomalies were present in all sample media (soil, vegetation and pisoliths) although the specific elements and tenor of the anomaly varied between sample media.
The results demonstrate a biotic (plant) influence on the dispersion of metallic elements at Golden Triangle prospect. This process of dispersion may serve to not only disperse and dilute metals in the regolith but potentially create a larger exploration target to detect the presence of the mineralisation. The anomalous metal content of the pisoliths themselves may be due to an earlier biotic mechanism of metal mobilisation from the deeper regolith or be solely a result of inorganic processes as previously thought. The sampling of deep-rooted trees and soil beneath them may assist in the discovery of mineral deposits in areas where there is transported material or leached regolith.
•Gold and other elements found in vegetation•First time published data of gold in iconic Australian trees and shrubs•Vegetation may be used as an indicator of mineralisation•Vegetation may disperse metals to form large geochemical anomalies
Recent trends in miniaturisation and high-strength fibrous composites encourage the use of mechanical micro-drilling technology of fibre-reinforced polymer composites (FRPs). Although severe ...expertise has been gained through the past few decades on the machinability of FRPs, this information cannot be directly adapted to the micro-drilling mainly due to the size effect. Therefore, the main aim of the present study is to comprehensively review challenges, recent experience, and future aspects of mechanical micro-drilling of glass and carbon fibre reinforced polymer (GFRP, CFRP) composites. The chip removal mechanisms of micro-drilling of FRPs are reviewed and compared to conventional-sized technologies. Furthermore, the micro-drilling-induced geometrical defects (delamination, burrs, fibre pull-outs etc.) and the cutting energetics are also discussed. Moreover, the future aspects and research directions are highlighted in this growing research area.
Display omitted
•Challenges of micro-drilling of fibrous composites were discussed and compared to macro-drilling.•Mechanisms of micro-drilling of FRPs are handled in an analogy of conventional drilling of FRPs considering CER.•The lack of information on the micro-drilling of FRPs is highlighted.•Future research directions and trends are discussed.
Cassiterite, rutile and gahnite from Scuddles VMS primary ore have accumulated residually in silcrete and in ferruginous lateritic zones (duricrust and gravel) that cap the weathering profile at ...Scuddles. Cassiterite and rutile contain inclusions of base metal sulfides and sulfosalts which are stable under alkaline and reducing conditions in the supergene sulfide enrichment zone, and alkaline to neutral conditions in the supergene oxide enrichment zone. However, cassiterite and rutile have been intensively corroded in the silcrete and lateritic zones under oxidizing conditions by acidic fluids derived by infiltration of acidic meteoric water and the oxidation of sulfide inclusions. This has resulted in releasing a suite of pathfinder elements, including Sn, Cu, Zn, Cd, Hg, Pb, Sb, Bi, W, Mo, Se and Te. The released Cu, Zn and Cd tend to be mobile under these conditions and are leached from the silcrete and lateritic zones. However, these elements are elevated at certain stratigraphic zones in silcrete and form surface anomalies in exposed saprolite. The other, less mobile elements, particularly Pb, Sb, Bi, W and Mo are concentrated in silcrete and ferruginous duricrust to form a variety of secondary microcrystalline phases of mixed or of unestablished mineralogy, including QRAZ (quartz, rutile, anatase, and zircon) and more complex Pb-, Ag-, Bi- and Sb-bearing phases. These pathfinder elements form a narrow, near-surface anomaly that delineates the Scuddles VMS deposit. This paper also reinforces findings that silcrete, ferruginous duricrust and ferruginous gravel are anomalous in pathfinder elements over the Scuddles deposit and, furthermore, are important sampling media in mineral exploration in general, particularly where gossans may not have formed or have been eroded.
•Geochemical anomaly in weathering profile above the VMS formed by accumulation of resistant minerals•Gahnite, cassiterite and rutile in leached and lateritic zones contain sulfide inclusions.•Weathering of cassiterite and rutile released pathfinder elements such as Pb, Bi and Sb.•Multi-element anomalies in leached and lateritic zones delineate the Scuddles VMS deposit.
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