Treatment of syphilis by arylarsonates

(1) The chief points about ATOXYL are its varying composition, its liability to contamination during the process of manufacture, its relative toxicity and its liability to decomposition under various physical and chemical conditions. Besides, there is its injurious action on the neuro-retinal visual apparatus. There is a conflict of opinion regarding its value. Although it is able to modify primary, secondary and various tertiary specific lesions, it fails in hereditary and parasyphilitic conditions. The fact that it sometimes succeeds where Mercury and the Iodides have failed, is no reason why it should be adopted as a routine mode of treatment in human Syphilis in view of the better results obtained by some of the newer arsenical preparations. The only conditions where it is likely to replace Mercury are in the various cases - already mentioned -- where that drug is contra-indicated or cannot be tolerated.(2) SOAMIN recommends itself to us on account of its definite chemical composition, its purity and relative non -toxicity. There is a unanimity of opinion as to its beneficial effects in primary, secondary and tertiary specific lesions. Authorities are also agreed as to its failure in hereditary and parasyphilitic conditions. It certainly succeeds where Mercury and the Iodides sometimes fail or are contra-indicated. Very seldom does it give rise to toxic effects or to visual disturbances. In conditions where Mercury is contra-indicated or useless, it is likely to replace it, and again in the Tropics where on account of the debility caused by climatic and malarial conditions it cannot be given. It certainly causes an increase in weight in almost every case and acts as a tonic in tropical debility. Its advantage over Mercury is that it causes no salivation, stomatitis or spongy gums. Likewise, in moderate remedial doses, it does not cause diarrhoea, a point of great value, as compared with Mercury, in the tropics where diarrhoea is such a prevalent disease or symptom.(3) ARSACETIN recommends itself to us on account of its purity, marked stability and the rapid manner in which it modifies all forms of the disease except hereditary and parasyphilitic ones. Compared with Soamin and Atoxyl, the weight of clinical evidence is 108. in its favour. It does not cause neuro-retinal ocular disturbances (like Atoxyl), is relatively nontoxic, well borne and certainly indicated where Mercury is useless or contra-indicated. When possible, it should be followed by a mercurial course, and is indicated in tropical conditions. Under its action, patients rapidly increase in weight and it acts indirectly as a tonic.Colonel Lambkin, in speaking of this drug and. Soamin, said that the good results he obtained in his cases strengthened his conviction that we had in them, a secondary specific for Syphilis, at least from a preventive and remedial point of view. As regards the former, he had then under his care cases with undoubted primary specific lesions which were treated with Soamin and which were closely observed every week for ten months without developing any further sign of the disease. From the remedial point of view the good results he obtained speak for it. But as a curative agent, it is beyond us all at present to give a positive answer to this all -important question; time and clinical experience alone would enable us to do so. This could not be done until it was proved beyond doubt that arylarsonates were capable of permanently expelling the spirochaetae pallida from the system, as indicated by the patient being rendored capable of re- infection. Neisser's successful experiments on apes from this point of view justified us in hoping for this end. Until the question as to the capability of arylarsonates bringing about a permanent cure was fully established, he would give Mercury after a course of treatment by arylarsonates. Later on, the same author(2)in speaking of the arylarsonates, said that our present knowledge of the power of these arsenical salts over Syphilis was in a very elementary stage, but he looked forward to further experience of them and improved technique leading us to that goal in the treatment of Syphilis which had already been attained with dourine. Regarding Arsacetin, Neisser(3)says that he has hitherto applied the mercurial and arsacetin treatment simultaneously, but perhaps they could be carried out alternately.(4) ARSENO-PHENYL-GLYCIN has been fully dealt with elsewhere and it only remains for me to say that, despite the brilliant results which follow its administration, there is no likelihood, on account of its instability and the inconvenient form in which it is supplied, of it ever replacing Mercury, and even other arylarsonates like Soamin, Arsacetin, Atoxylate of Mercury and Salvarsan in the treatment of human Syphilis.In reviewing the arylarsonates hitherto discussed and used before the introduction of Salvarsan and Mercury Atoxylate, Colonel Lambkin said that it was far too soon to express an opinion as to whether they were likely to prove of permanent benefit in Syphilis or whether they were likely to replace Mercury in the disease, but the results were encouraging. Whether they had any abortive or prophylactic effect on the future development of the disease after inoculation, he was unable to speak except to note that when given at an early date they delayed and modified considerably the secondary signs of the disease and that they had very beneficial effects on all specific mucous ulcerations. It was well established, he thought, that in the arylarsonates we had a second specific for Syphilis, the importance of which could not well be exaggerated.(5) In MERCURY ATOXYLATE we have a very potent drug exerting both the specific actions of Atoxyl and Mercury on the spirochaetae, both in vitro and in corpore. It is far more potent than Calomel injections alone. If applied to suitable cases and care taken in its administration, it is a safe drug. Lambkin and others who have used it, prefer it to Mercury over which it has a decided advantage in the rapidity with which it controls the symptoms of the disease. I am of opinion that this drug will certainly displace the mercurial treatment of Syphilis.(6) SALVARSAN or Ehrlich Hata's "606" is the most potent drug hitherto discovered and applied to the treatment of human Syphilis in its protean aspects. Its stability, non -toxicity, ease of administration, rapidity of action, the fact that it does not affect the neuro-retinal visual apparatus, all speak in its favour. It is indicated in all forms of the disease viz. primary, secondary, tertiary and hereditary lues, while it has a marked effect in combating some of the symptoms occurrinm_ in parasyphilis. It has yielded marvellous results in alleviating the various crises of locomotor ataxia of specific origin. With the doses at present used, cases have been said to recur, but Professor Herxheimer, Dr H. Isaac and others have never seen them. Dr Leonor Michaelis found that the recovery was absolute in a few days in most of his cases, while Dr Gourwitsch and S. Bormann selected cases which had been treated with the most powerful of mercurial methods and found that the comparison of these with Arseno-benzol proved the over-whelming value of the latter.By way.of conclusion, I may say that from a personal experience of the effects produced by Salvarsan and the reports of eminent authorities, that the drug is absolutely superior in Syphilis to any other known drug, and. that a single injection, in a suitable case, will produce results obtained only after years of_ treatment with Mercury. This latter drug, however, is not to be discarded because it seems to have been proved that there are strains of spiroçhaetaç that are arsenic-proof. In the same way, there are strains that are Mercury-proof. Perhaps by using one drug after the other we may be able to destroy all these various strains and so bring about a permanent cure of the disease.In spite of the pre-eminence of Salvarsan as the best curative and prophylactic agent hitherto discovered for Syphilis, I venture to state that the last word has not yet been spoken on the treatment of. Syphilis

Propagation of social representations

Based on a minimal formalism of social representations as a set of associated cognems, a simple model of propagation of representations is presented. Assuming that subjects share the constitutive cognems, the model proposes that mere focused attention on the set of cognems in the field of common conscience may replicate the pattern of representation from context into subjects, or, from subject to subject, through actualization by language, where cognems are represented by verbal signs. Limits of the model are discussed, and evolutionist perspectives are presented with the support of field data

Improving surface current resolution using direction finding algorithms for multiantenna high-frequency radars

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of the Atmospheric and Oceanic Technology 36(10), (2019): 1997-2014, doi: 10.1175/JTECH-D-19-0029.1.While land-based high-frequency (HF) radars are the only instruments capable of resolving both the temporal and spatial variability of surface currents in the coastal ocean, recent high-resolution views suggest that the coastal ocean is more complex than presently deployed radar systems are able to reveal. This work uses a hybrid system, having elements of both phased arrays and direction finding radars, to improve the azimuthal resolution of HF radars. Data from two radars deployed along the U.S. East Coast and configured as 8-antenna grid arrays were used to evaluate potential direction finding and signal, or emitter, detection methods. Direction finding methods such as maximum likelihood estimation generally performed better than the well-known multiple signal classification (MUSIC) method given identical emitter detection methods. However, accurately estimating the number of emitters present in HF radar observations is a challenge. As MUSIC’s direction-of-arrival (DOA) function permits simple empirical tests that dramatically aid the detection process, MUSIC was found to be the superior method in this study. The 8-antenna arrays were able to provide more accurate estimates of MUSIC’s noise subspace than typical 3-antenna systems, eliminating the need for a series of empirical parameters to control MUSIC’s performance. Code developed for this research has been made available in an online repository.This analysis was supported by NSF Grants OCE-1657896 and OCE-1736930 to Kirincich, OCE-1658475 to Emery and Washburn and OCE-1736709 to Flament. Flament is also supported by NOAA’s Integrated Ocean Observing System through Award NA11NOS0120039. The authors thank Lindsey Benjamin, Alma Castillo, Ken Constantine, Benedicte Dousset, Ian Fernandez, Mael Flament, Dave Harris, Garrett Hebert, Ben Hodges, Victoria Futch, Matt Guanci, and Philip Moravcik for assistance in building, deploying, and operating the radars.2020-04-1

Provenance of plumes in global convection models

In global convection models constrained by plume motions and subduction history over the last 230 Myr, plumes emerge preferentially from the edges of thermochemical structures that resemble present-day large low shear velocity provinces (LLSVPs) beneath Africa and the Pacific Ocean. It has been argued that large igneous provinces (LIPs) erupting since 200 Ma may originate from plumes that emerged from the edges of the LLSVPs and numerical models have been devised to validate this hypothesis. Although qualitative assessments that are broadly in agreement with this hypothesis have been derived from numerical models, a quantitative assessment has been lacking. We present a novel plume detection scheme and derive Monte Carlo-based statistical correlations of model plume eruption sites and reconstructed LIP eruption sites. We show that models with a chemically anomalous lower mantle are highly correlated to reconstructed LIP eruption sites, whereas the confidence level obtained for a model with purely thermal plumes falls just short of 95%. A network of embayments separated by steep ridges form in the deep lower mantle in models with a chemically anomalous lower mantle. Plumes become anchored to the peaks of the chemical ridges and the network of ridges acts as a floating anchor, adjusting to slab push forces through time. The network of ridges imposes a characteristic separation between conduits that can extend into the interior of the thermochemical structures. This may explain the observed clustering of reconstructed LIP eruption sites that mostly but not exclusively occur around the present-day LLSVPs

Correspondence: Reply to ‘Numerical modelling of the PERM anomaly and the Emeishan large igneous province’

Tectonic plates and plate boundaries migrate substantially through time and mantle plumes are generally accepted to be mobile within the convecting mantle, but it has been proposed that large low shear velocity provinces (LLSVPs) could have been fixed and rigid for as much as 540 million years (Myr). The hypotheses of fixed and rigid LLSVPs cannot be easily tested in the absence of constraints on the past location of lowermost mantle structures. We evaluated the hypothesis9of lower mantle thermochemical structure fixity with numerical experiments. As in earlier studies, we argue that the location of lower mantle thermochemical structures has changed through time

Origin and evolution of the deep thermochemical structure beneath Eurasia

A unique structure in the Earth’s lowermost mantle, the Perm Anomaly, was recently identified beneath Eurasia. It seismologically resembles the large low-shear velocity provinces (LLSVPs) under Africa and the Pacific, but is much smaller. This challenges the current understanding of the evolution of the plate–mantle system in which plumes rise from the edges of the two LLSVPs, spatially fixed in time. New models of mantle flow over the last 230 million years reproduce the present-day structure of the lower mantle, and show a Perm-like anomaly. The anomaly formed in isolation within a closed subduction network ∼22,000 km in circumference prior to 150 million years ago before migrating ∼1,500 km westward at an average rate of 1 cm year^(−1), indicating a greater mobility of deep mantle structures than previously recognized. We hypothesize that the mobile Perm Anomaly could be linked to the Emeishan volcanics, in contrast to the previously proposed Siberian Traps

Differential roles of p39Mos–Xp42Mpk1 cascade proteins on Raf1 phosphorylation and spindle morphogenesis in Xenopus oocytes

AbstractFully-grown G2-arrested Xenopus oocytes resume meiosis upon hormonal stimulation. Resumption of meiosis is characterized by germinal vesicle breakdown, chromosome condensation, and organization of a bipolar spindle. These cytological events are accompanied by activation of MPF and the p39Mos–MEK1–Xp42Mpk1–p90Rsk pathways. The latter cascade is activated upon p39Mos accumulation. Using U0126, a MEK1 inhibitor, and p39Mos antisense morpholino and phosphorothioate oligonucleotides, we have investigated the role of the members of the p39Mos–MEK1–Xp42Mpk1–p90Rsk in spindle morphogenesis. First, we have observed at a molecular level that prevention of p39Mos accumulation always led to MEK1 phosphorylation defects, even when meiosis was stimulated through the insulin Ras-dependent pathway. Moreover, we have observed that Raf1 phosphorylation that occurs during meiosis resumption was dependent upon the activity of MEK1 or Xp42Mpk1 but not p90Rsk. Second, inhibition of either p39Mos accumulation or MEK1 inhibition led to the formation of a cytoplasmic aster-like structure that was associated with condensed chromosomes. Spindle morphogenesis rescue experiments using constitutively active Rsk and purified murine Mos protein suggested that p39Mos or p90Rsk alone failed to promote meiotic spindle organization. Our results indicate that activation of the p39Mos–MEK1–Xp42Mpk1–p90Rsk pathway is required for bipolar organization of the meiotic spindle at the cortex

Elongation of confined ferrofluid droplets under applied fields

Ferrofluids are strongly paramagnetic liquids. We study the behavior of ferrofluid droplets confined between two parallel plates with a weak applied field parallel to the plates. The droplets elongate under the applied field to reduce their demagnetizing energy and reach an equilibrium shape where the magnetic forces balance against the surface tension. This elongation varies logarithmically with aspect ratio of droplet thickness to its original radius, in contrast to the behavior of unconfined droplets. Experimental studies of a ferrofluid/water/surfactant emulsion confirm this prediction.Comment: 12 pages, 7 figures. Submitted to Phys. Rev.