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Only few therapeutic options exist for patients with refractory sudden idiopathic sensorineural hearing loss (SISHL). Little is known about the efficacy of second-line therapies. Rheopheresis seems to be an effective therapeutic possibility. Between 2012 and 2015, 106 patients with SISHL were enrolled in the study, of whom 52 were refractory to initial treatment. As salvage therapy, these patients were offered either 3 sessions of rheopheresis (33 pts) or intratympanic steroid treatment through MicroWick application (19 pts). Pure tone audiometry was performed at diagnosis, at the 1st month and the 1st year during the follow-up. Patients in the rheopheretic arm had higher hearing loss than in the MicroWick arm (81% vs. 52%, p= 0.04). In spite of this, there was a significant improvement for patients in the rheopheretic arm (27% of hearing loss reduction, p< 0.001) after the 1st month and this remained unchanged during the 1st year, while no improvement was seen in the MicroWick arm (0% of hearing loss reduction, p= 0.424). We found no predictive factor for steroid-failure in first-line therapy. Older age (p= 0.003), presence of vertigo (p= 0.006) and more profound initial hearing loss (p< 0.001) were identified as negative prognostic markers. Rheopheresis can be used as a potentially effective and safe salvage therapy for patients with cortico-refractory SISHL.

Generalization in meta-analyses is not a dichotomous decision (typically encountered in papers using the Qtest for homogeneity, the 75% rule, or null hypothesis tests). Inattention to effect size variability in meta-analyses may stem from a lack of guidelines for interpreting credibility intervals. In this commentary, we describe two methods for making practical interpretations and determining whether a particular SDρ represents a meaningful level of variability.

The article describes an experimental investigation of scale effect in a starved elastohydrodynamically lubricated contact on lubricant film thickness. Lubricant film thickness and its distribution is one of the most important parameters determining the performance and life of machine parts. Current experimental and numerical studies are mostly connected with oil lubrication. However, greases are used in more than 80 % of all rolling bearings where the starvation phenomenon occurs most frequently. The aim of this work is to compare two approaches to measuring film thickness of different greases. The use of multiple contacts optical test rig based on thin film colorimetric interferometry for film thickness measurement has enables to obtain film thickness of starved contact and the film distribution. The experimental observation of full-scale model of bearing will help to understand better the behavior of real bearing. The evaluation of the experiment was made by chromatic interferometry. This method is used to measure thin lubrication films.

A dominant general factor (DGF) is present when a single factor accounts for the majority of reliable variance across a set of measures (Ree, Carretta, & Teachout, 2015). In the presence of a DGF, dimension scores necessarily reflect a blend of both general and specific factors. For some constructs, specific factors contain little unique reliable variance after controlling for the general factor (Reise, 2012), whereas for others, specific factors contribute a more substantial proportion of variance (e.g., Kinicki, McKee-Ryan, Schriesheim, & Carson, 2002). We agree with Ree et al. that the presence of a DGF has implications for interpreting scores. However, we argue that the conflation of general and specific factor variances has the strongest implications for understanding how constructs relate to external variables. When dimension scales contain substantial general and specific factor variance, traditional methods of data analysis will produce ambiguous or even misleading results. In this commentary, we show how several common data analytic methods, when used with data sets containing a DGF, will substantively alter conclusions.

The ability to estimate chemical and physical properties from experimental spectra is highly desirable, as it eliminates the need for a priori knowledge of exact chemical structure and allows the property estimation of mixtures. Here we report the proof of principle that a predictive method for octanol‐water partition coefficient (logP) based on 1H‐NMR spectra in d3‐chloroform is feasible and can yield accuracy comparable to in silico logPmodels. The Spectrometric Data‐Activity Relationship (QSDAR) reported predicts logPof neutral organic chemicals using descriptors derived only from 1H‐NMR chemical shifts, integrations and peak widths. Proton NMR spectra of 140 compounds with diverse structures were used to construct a Multiple Linear Regression (MLR) and a Partial Least Squares (PLS) model that predicts logP.The optimized models were internally validated by K‐fold cross validation and leave‐one‐out validation, and externally with a test set of 28 chemicals. The squared regression coefficients of prediction for the MLR and PLS regression models were 0.970 and 0.971 respectively, showing that the method allows accurate prediction of logPvalues exclusively from predicted 1H NMR spectra.

Summary. Background:Little information is available on the long‐term clinical outcome of cerebral vein thrombosis (CVT).

Present situation in the industrial manufacture has brought new trends in the kind of flexibility and intelligence. That means new generation of intelligent manufacturing systems. New generation of clamping fixtures is represented by group of clamping fixtures which can be used in intelligent manufacturing systems.

The main advantage of the flexible manufacturing system is its high flexibility in management of production facilities and resources (time, machines and their utilization, etc.). The largest application of these systems is in the area of small batch production where its efficiency is getting near to the mass production efficiency. Its disadvantage is the high implementation price.

This paper presents a Hybrid Iterative Local Search Heuristic and its framework, whose aim lies on helping to escape from local optima when a construction heuristic, for the VRP, has been trapped. The approach was mainly inspired by basic and modified versions of related successfully applied heuristics such as Variable Neighborhood Search (VNS) and Granular Local Search (GLS). Differently to a great deal of local search heuristics revised, which mainly consider a single decision criterion, multiple optimization criteria are considered all along the local search and a Multiple Criteria Threshold has been proposed allowing defining which arcs must be included in a candidate list to explore, this considerably reduces the search area and has a major incidence in the satisfaction of the clients. The proposal is enriched with a good literature review, taking into account some of the gaps and achievements of the states of the art and practice.

In August 1945, Karl Loewenstein began work as senior expert advisor to the Legal Division of American Military Government (AMG) in Berlin. An eminent German-born and educated political scientist and jurisprudent, Loewenstein had come to assist in the “democratization” of his homeland's Nazified law and legal institutions. It was soon obvious, however, that in its crucial first phase the American legal mission in Germany was in disarray. The development and implementation of American law reform policy was being undercut by ill-prepared leadership, poor planning, and the scarcity of learning about German laws, lawyers, and legal history. By Loewenstein's reckoning, many American officers had been “set to work on problems of which they have not the slightest idea and very little professional qualification.” Critical law reform initiatives had been based upon expedient “over-simplifications” of Nazism and its eradication. By January 1946, his initial misgivings having given way to mordant despair, Loewenstein concluded that the American program for the democratization of the German legal system was irrevocably “lost,” a “failure which stinks to high heaven.” This article sets forth the theoretical and observational bases of Loewenstein's assessment and evaluates its cogency.

This protocol presents a new method to purify plasmid DNA using temperature-triggered precipitation. The principle is based on the specific DNA-binding affinity of a bacterial metalloregulatory (MerR) protein to its cognate DNA sequence and the temperature responsiveness of elastin-like protein (ELP). A bifunctional ELP-MerR fusion protein is created to enable the precipitation of plasmid DNA, designed to contain the MerR recognition sequence, by a simple temperature trigger. The protocol covers all stages of the process from the design of ELP-MerR fusion proteins and MerR-binding plasmids, to the isolation of plasmid DNA from Escherichia coli cultures after boiling lysis, the subsequent temperature-triggered precipitation of plasmid DNA-fusion protein complexes and final elution of plasmid DNA by mild heating. This protocol is well suited to laboratory research-scale applications, producing plasmid DNA of better purity and similar yield as one of the most commonly used laboratory methods, standard alkaline lysis (known as the midiprep procedure). The protocol takes approximately 30 min to obtain pure plasmid DNA from cell cultures using the temperature-triggered precipitation method.

Spontaneous firing of olfactory receptor neurons (ORNs) was recently shown to be required for the survival of ORNs and the maintenance of their appropriate synaptic connections with mitral cells in the olfactory bulb. ORN spontaneous activity has never been described or characterized quantitatively in mammals. To do so we have made extracellular single unit recordings from ORNs of freely breathing (FB) and tracheotomized (TT) rats. We show that the firing behavior of TT neurons was relatively simple: they tended to fire spikes at the same average frequency according to purely random (Poisson) or simple (Gamma or Weibull) statistical laws. A minority of them were bursting with relatively infrequent and short bursts. The activity of FB neurons was less simple: their firing rates were more diverse, some of them showed trends or were driven by breathing. Although more of them were regular, only a minority could be described by simple laws; the majority displayed random bursts with more spikes than the bursts of TT neurons. In both categories bursts and isolated spikes (outside bursts) occurred completely at random. The spontaneous activity of ORNs in rats resembles that of frogs, but is higher, which may be due to a difference in body temperature. These results suggest that, in addition to the intrinsic thermal noise, spontaneous activity is provoked in part by mechanical, thermal, or chemical (odorant molecules) effects of air movements due to respiration, this extrinsic part being naturally larger in FB neurons. It is suggested that spontaneous activity may be modulated by respiration. Because natural sampling of odors is synchronized with breathing, such modulation may prepare and keep olfactory bulb circuits tuned to process odor stimuli. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005

The article discusses that the use of Microelectromechanical System actuators to adjust the optical properties of nano-optics devices will provide a viable platform for tunable optical filters. The electronically controllable nano-optic devices allow the adjustment of optical power, polarization, phase, focal point, direction and transmitted or reflected wavelength. A nano-optic tunable filter taps an optical signal and together with a photodetector can be used to detect power and wavelength drift for WDM channels.

Tunable biopolymers were synthesized for the removal of heavy metals from dilute waste streams. Protein−protein interaction was tailored specifically into tunable, metal-binding biopolymers using elastin-like polypeptides composed of either one or two hexahistidine clusters. These tunable biopolymers retained the functionality of the elastin domain, undergoing a reversible phase transition above the transition temperature. Aggregation could be tuned within a wide range of temperatures by controlling the chain length of the biopolymers. The presence of the histidine clusters enabled Cd²⁺ to bind strongly to the biopolymers. Recovery of biopolymer−Cd²⁺ complexes was easily achieved by triggering aggregation either by raising temperature or by salt addition. Regenerated biopolymers could be reloaded with Cd²⁺ and reused for repeated cycles with similar efficiency. This system is very flexible as both domains can be engineered to respond to various phase transition conditions and to provide various levels of metal-binding selectivity. The ability to modulate the properties of the biopolymers simply by tuning process conditions should open up new opportunities for the separation and recovery of other environmental contaminants.

Diapause larvae of Aphidoletes aphidimyzawere stored at a temperature of 3°C under continuous darkness for up to 7 months with survival rates above 50%; after storage for 1 year the survival rate dropped to 12%. Diapause was terminated in the majority of individuals within 120 days of chilling under storage conditions. Brief exposure (10–60 s) to the vapor of n-hexane appeared to be a useful alternative to chilling for the termination of diapause. The larvae with terminated diapause required, on average, an additional 31 days at 22°C and long-day conditions in order to reach the adult stage. The 10–90% adult emergence spanned a period of 21.1 days. When the larvae with terminated diapause were exposed to 30°C for 1 week after the end of low temperature storage, the survival rate was not affected, the average “time-to-adult” shortened moderately to 28 days, and the synchrony of adult emergence improved considerably to 10 days. Low temperature storage of nondiapause larvae resulted in a decrease in survival from 98 to 31% during the first 60 days of storage. Nondiapause larvae did not enter diapause during low temperature storage and, as a consequence, the adults emerged relatively rapidly (after 14–15 days) and synchronously (within 2–3 days) after the end of storage. Directions for future research, which might bring further improvement in low temperature storability and synchrony of adult emergence in A. aphidimyza, are proposed.

Introduction:Key characteristics of immune thrombocytopenia (ITP) include immune-mediated platelet destruction/impaired production, with resultant thrombocytopenia and increased bleeding risk. Durable response to current therapies remains an unmet need, particularly in the relapsed/refractory setting. Rilzabrutinib is the first oral, reversible, covalent inhibitor of Bruton tyrosine kinase designed to target immune-mediated pathways in ITP without inhibiting normal platelet aggregation. Initial phase I/II results in ITP demonstrated rapid and durable efficacy with rilzabrutinib that was well-tolerated at all dose levels, including the optimal 400 mg bid dose. Interim results on rilzabrutinib effects in patients with relapsed/refractory ITP were previously reported. Here we present long-term data from a larger group of patients who initiated rilzabrutinib at 400 mg bid and are continuing in the long-term extension (LTE) period.

We demonstrate that a mucoid, alginate-producing strain of Pseudomonas aeruginosa isolated from the lungs of a cystic fibrosis (CF) patient secretes multiple enzymes with nucleoside diphosphate kinase (Ndk), ATPase, adenylate kinase, 5'-nucleotidase, and ATP-modifying enzymatic activities. The secretion is triggered at high cell density and in complex media but is greatly reduced when the mucoid cells are grown in mineral salts media or in presence of 5.0 mM Ca2+ or Mg2+. Interestingly, the secretion is triggered primarily in the mucoid CF isolate of strain 8821M (or in strain FRD1) but not in a nonmucoid laboratory strain, PAO1. The purified secreted Ndk shows 100% match in its N-terminal amino acid sequence with that of purified intracellular Ndk and demonstrates similar enzymatic properties. The N-terminal sequence of the purified ATPase isolated from an ndk knockout mutant shows its identity with that of the heat shock chaperonin Hsp60. During fractionation, the flowthrough fraction from a Mono Q column demonstrates the presence of 5'-nucleotidase, adenylate kinase, and a putative ATP reductase activity. These fractions demonstrate high cytotoxic activities for murine peritoneal primary macrophages which can be further stimulated in the presence of ATP or inhibited by pretreatment of macrophages with oxidized ATP (oATP). The cytotoxicity associated with ATP-induced stimulation is believed to be due to activation of macrophage surface-associated P2Z (P2X7) receptors, which are one of the purinergic receptors responsible for pore formation on macrophage membrane. Blocking of these receptors by pretreatment with oATP blocks ATP-induced macrophage cell death. Thus mucoid P. aeruginosa cells elaborate enzymes that modulate the external ATP levels of macrophages, thereby modulating macrophage cell death through P2Z receptor activation. Evidence for the presence of secreted cytotoxic agents that act independently of P2Z receptor activation is also presented.

ABSTRACTWe demonstrate that a mucoid, alginate-producing strain ofPseudomonas aeruginosaisolated from the lungs of a cystic fibrosis (CF) patient secretes multiple enzymes with nucleoside diphosphate kinase (Ndk), ATPase, adenylate kinase, 5′-nucleotidase, and ATP-modifying enzymatic activities. The secretion is triggered at high cell density and in complex media but is greatly reduced when the mucoid cells are grown in mineral salts media or in presence of 5.0 mM Ca2+or Mg2+. Interestingly, the secretion is triggered primarily in the mucoid CF isolate of strain 8821M (or in strain FRD1) but not in a nonmucoid laboratory strain, PAO1. The purified secreted Ndk shows 100% match in its N-terminal amino acid sequence with that of purified intracellular Ndk and demonstrates similar enzymatic properties. The N-terminal sequence of the purified ATPase isolated from an ndkknockout mutant shows its identity with that of the heat shock chaperonin Hsp60. During fractionation, the flowthrough fraction from a Mono Q column demonstrates the presence of 5′-nucleotidase, adenylate kinase, and a putative ATP reductase activity. These fractions demonstrate high cytotoxic activities for murine peritoneal primary macrophages which can be further stimulated in the presence of ATP or inhibited by pretreatment of macrophages with oxidized ATP (oATP). The cytotoxicity associated with ATP-induced stimulation is believed to be due to activation of macrophage surface-associated P2Z (P2X7) receptors, which are one of the purinergic receptors responsible for pore formation on macrophage membrane. Blocking of these receptors by pretreatment with oATP blocks ATP-induced macrophage cell death. Thus mucoid P. aeruginosacells elaborate enzymes that modulate the external ATP levels of macrophages, thereby modulating macrophage cell death through P2Z receptor activation. Evidence for the presence of secreted cytotoxic agents that act independently of P2Z receptor activation is also presented.

The historiography of work-related accidents in nineteenth-century Ontario is a product of two complementary but as yet unsynthesized lines of inquiry. On the one hand, legal historians have focused on the genesis of judge-made and statutory law respecting the liability of employers for the work-related accidents of their hired labor. Considerable light has been shed on political and ideological as well as formally ?legal? factors that shaped judicial and legislative decision making concerning personal injuries at work. However, the legal historiography of the Victorian Ontario workplace pertains mainly to the law and those who made the law, rather than those subject to it. These studies of the dynamics of legal change, important as they are, lack a firm basis in tangible sociohistorical experience.

F.W. Maitland. G.R. Elton. London. 1985. Weidenfeld and Nicolson. vii & 118 pp. (incl. Index). £12.95.Victorian Prison Lives: English Prison Biography (1830-1914). Philip Priest-ley. London and New York. 1985. Methuen. xiii & 311 pp. (incl. index). £25.00.Christopher St German on Chancery and Statute. J.A. Guy. London. 1985. Selden Society Supplementary series vol. 6. x & 149 pp. (incl. index). £15.Imprisonment in England and Wales: A Concise History, Christopher Harding, Bill Hines, Richard Ireland and Philip Rawlings, Beck-enham. Croom Helm. 1985. xiii & 308 pp. £25.00.The Evolution of Law. Alan Watson. Oxford. 1985. Basil Blackwell. xi & 156 pp. (incl. index). £17.50.Unequal Access: Women Lawyers in a Changing America. Ronald Chester. Massachusetts. 1985. Bergin & Garvey Publishers, Inc. viii & 135 pp.(incl. index). £24.95.Unequal Laws unto a Savage Race: European Legal Traditions in Arkansas, 1686-1836. Morris S. Arnold. Fayetteville. 1985. University of Arkansas Press, xviii & 234 pp.Returns of Strangers in the Metropolis 1593, 1627, 1635, 1639: A Study of an Active Minority. Ed. Irene Scouloudi. London. 1985. The Huguenot Society.'Without the Law': Administrative Justice and Legal Pluralism in Nineteenth Century England. H.W. Arthurs. Toronto. 1985. University of Toronto Press, xvi + 312 pp. (incl. index). £20.00.

To elucidate mechanisms involved in the regulation of lung collagen content we studied hamsters with bleomycin-induced pulmonary fibrosis. Lung collagen in this model is increased as the result of greatly increased lung collagen synthesis rates. However, collagen synthesis rates are subsequently restored to normal. Hamster lung explants from both normal and bleomycin-exposed hamsters were cultured, and the effects of explant conditioned medium (CM) on lung fibroblast (IMR-90) proliferation and collagen production in vitro were determined. Lung explant CM increased fibroblast prostaglandin (PG)E2 production and intracellular cAMP, and decreased both fibroblast proliferation and collagen production in a dose-dependent manner. Greater activity was observed with lung explant CM from bleomycin-exposed lungs. Incubation of fibroblasts with indomethacin prior to addition of CM blocked CM-mediated changes in PGE2 and cAMP and inhibited changes in fibroblast proliferation and collagen production. Exogenous PGE2 or dibutyryl cAMP also suppressed fibroblast proliferation and collagen production. The suppressive activity in lung-conditioned medium is nondialyzable, has an apparent molecular weight of 15,000-20,000 by gel filtration, and is heat-stable. It is not species-restricted since CM from hamster lung affected human and hamster lung fibroblasts similarly. Activity is present preformed in lung and bronchoalveolar lavage fluid, although bronchoalveolar macrophages produce a nondialyzable factor in culture which suppresses fibroblast proliferation. The suppressive activity identified in fibrotic lung may represent a means for limiting collagen accumulation following tumor injury.

The article discusses a court case wherein Abby Wambach and 40 other players on national teams participating in the International Federation of Association Football (FIFA) Women's World Cup Canada 2015 filed an application on October 1, 2014 with the Ontario Human Rights Tribunal against FIFA and the Canadian Soccer Association over the use of artificial turf in the upcoming tournament. Topics mentioned include a legal analysis of the case, its legal framework, and its key concessions.

Correct mathematical models of a reactor core in benchmarking of reactor physics experiments require detailed knowledge of exact isotopic composition of fuel pellets, especially the presence of neutron absorbers. Among them, knowledge of 234U and 236U abundance in fuel is important, because their absorption is considerably stronger than that of the most common 238U and their concentration is significantly higher than any other absorbers. Thus, the fuel pellets used in the nuclear research reactor LR-0 have been experimentally investigated using the procedure that involves a method of secondary ion mass spectrometry (SIMS), which allowed for analyses of miniature amount of the pellet material without disturbing its integrity. The pellets were swiped with cotton cloths and the microscopic particles collected on the cloth were analyzed. The isotopic composition of individual uranium particles then provided information required for the reactor core modeling and in addition to that some hints about used source materials, history of nuclear material, and the manufacturing process of the pellets.

The paper summarizes the issue of the validation of the silicon-filtered neutron beam transport in the structural materials important for nuclear technology. Iron, which is the most common material in the reactor technology was tested. The silicon filtered beam itself is a very interesting tool, because some significant peaks occur in the spectrum, helping to study the deep neutron transport in the steel. The character of spectrum is reflecting the silicon cross section in region 1 - 8 MeV. Because it has got a fine character, the peaks in neutron spectrum are occurring in the positions of the cross section depressions. Based on the agreement between calculated and measured attenuation in groups located within the neutron flux peaks one can reveal possible problems in neutron transport description. These results constitute a good addition to integral experiments characterizing the neutron transport in steel using 252Cf(s.f) and 235U(nth;fiss) which both have got a smooth spectrum.

Neutron field shaping is the suitable method for validation of cross-sections in various energy regions. By increasing the share of neutrons of a certain energy interval and decreasing the share of other, a reaction becomes more sensitive to selected neutrons. As a result, reaction cross-sections can be validated in selected energy regions more precisely. The shaping can be carried out by both neutron filters which are materials with high absorption in some energy region, or by diffusion material changing the shape of neutron spectra by means of slowing down process. In the presented experiments the neutron field of the LR-0 reactor was shaped by both using graphite blocks inserted into the core and Cd cladding for increasing the epithermal reaction rate share in total reaction rates. The calculations were carried out with the MCNP6 code and the most recent nuclear data libraries. The results in the pure graphite neutron field are in good agreement, in case of Cd cladding, significant discrepancies were reported. In case of the 23Na(n, γ) reaction, over-estimation by about 14 % was reached in IRDFF2, results in other libraries are comparable. In case of 58Fe(n, γ) the overestimation as high as18 % is reported in IRDFF-2. For 64Zn(n,γ) reasonable agreement was reached in ENDF/B-VIII, where discrepancies in pure graphite neutron field or in case of Cd cladding, are about 10 - 15%.

Dosimetry of high doses of ionizing radiation is a method widely used not only in the field of basic and applied research but also in various industries. High-dose irradiation is used in the sterilization of foodstuffs and prolongation of their shelf life, sterilization of tools, materials and wastewater, treatment of antiquities attacked by woodworm organisms, biological and genetic research, inhibition of seed germination and retardation of fruit ripening. Furthermore, it has been applied in radiation resistance testing of materials, defectoscopy, industrial irradiation of materials (e.g. crosslinking and grafting of polymers or gemstone coloring by ionizing radiation), and last but not least, of course, nuclear energetics. In this work the dosimetric properties of polycarbonate are studied. They are compared with a standardized and certified method using alanine dosimeters. In the case of gammas the testing was realized for 60Co and neutron radiation was studied in the research nuclear reactor LVR-15.

Features the subwavelength optical elements (SOE). Physics of the interaction of optical-processing functions; Application of nanotechnology on optical element; Flexibility of SOE for telecommunications applications.