Optic neuritis and multiple sclerosis (MS) are common causes of visual and neurologic dysfunction in young adults. Advances in magnetic resonance imaging, molecular genetics, and neuroimmunology have increased our understanding of the pathophysiology underlying both disorders. Corticosteroids remain the mainstay of treatment of optic neuritis, but alternate dosages and routes of administration are undergoing investigation. The available therapies for MS have expanded, and there is evidence that early intervention is beneficial. Treatments for MS show sustained efficacy, but are not curative, and adjunctive treatments may prove valuable in patients with progressive visual and neurologic disability.


In this study, sputtered indium-tin-oxide (ITO) formed ITO/Au/ITO was used to form composite transparent gate InAlAs-InGaAs metamorphic HEMTs (CTG-MHEMT), with an optoelectronic mixer significantly markedly improved front-side optical coupling efficiency. The proposed CTG-MHEMT exhibits a high responsivity (λ = 1310 nm) of 1.71 A/W under optimal bias conditions. A -3 dB electrical bandwidth of 400 MHz is produced by the photovoltaic effect and dominated by the long lifetime of the excess holes. The -3 dB electrical bandwidth associated with the photoconductive effect is 2.3 GHz, and is determined mainly by the short electron life time. A power gain cut-off frequency (fmax) of CTG-MHEMT of 18.2 GHz was achieved. This value, is much larger than that of TG-MHEMT (14.6 GHz) because Au nano particles improved the gate resistance. The optoelectronic mixing efficiency was enhanced by tuning the gate bias conditions. The CTG-MHEMT optoelectronic mixer is a cost-effective device, and based on the optical and electrical characteristics, is a promising candidate for simplifying the system architecture in fiber-optic microwave transmission applications.


The question of whether Canadian lawyers ought to be trusted to govern themselves has been repeatedly raised by the public, policy-makers and the academy over the past several decades. The legal profession has responded on a number of fronts, adopting what has been characterized as a "regime of defensive self-regulation." The analysis in this article complements and complicates this account by arguing that, alongside the profession's efforts at defensive self-regulation, there has been a steady stream of aggressive judicial regulation. The central argument of this article is two-fold: first, that courts have come to occupy an increasingly active role as regulators of the Canadian legal profession in the past several decades; and, second, that the measures taken by the courts have resulted in a regulatory regime more attentive to the public interest. In advancing these arguments, this article seeks not only to present a more accurate picture of the current status of lawyer regulation in Canada but also to provide a better foundation from which to discuss future reforms.


Non-carious cervical tooth loss is not always attributable to a single causative factor, as evidenced by the numerous terminologies used. In this, the first of two articles, the aetiology and prevalence of non-carious tooth loss are discussed. Guidelines are suggested as to how it may be diagnosed, prevented and monitored. A further article will cover the restorative management.


Cost, safety, and cycle life have emerged as prime concerns to build robust batteries to cater to the global energy demand. These concerns are impacted by all battery components, but the realizable energy density of lithium‐ion batteries (LIBs) is limited by the performance of cathodes. Thus, cathode materials have a significant role to play in advancing the performance and economics of secondary batteries. To realize next generation Li‐ion and post Li‐ion batteries, a variety of cathode insertion materials have been explored, but finding a cost effective and stable cathode material that can deliver high energy density has been a daunting task. Oxide cathode materials are ubiquitous in commercial applications, as they can deliver high capacity. In comparison, polyanionic insertion materials can offer tuneable (high) redox potential, operational safety, and structural as well as thermal stability. Indeed, a wide range of polyanionic materials like phosphates, borates, sulfates, and their complexes have been reported. In this article, the alkali metal fluorophosphates class of polyanionic cathodes for secondary batteries is discussed. The various reported fluorophosphate insertion materials are discussed in terms of their electrochemical and electrocatalytic properties. The historical overview, recent progress, and remaining challenges for polyanionic fluorophosphates are presented along with suggested future research directions and potential application.


In this paper, we consider iterative algorithms of Uzawa type for solving linear nonsymmetric saddle point problems. Specifically, we consider systems, written as usual in block form, where the upper left block is an invertible linear operator with positive definite symmetric part. Such saddle point problems arise, for example, in certain finite element and finite difference discretizations of Navier-Stokes equations, Oseen equations, and mixed finite element discretization of second order convection-diffusion problems. We con- sider two algorithms, each of which utilizes a preconditioner for the operator in the upper left block. Convergence results for the algorithms are established in appropriate norms. The convergence of one of the algorithms is shown as- suming only that the preconditioner is spectrally equivalent to the inverse of the symmetric part of the operator. The other algorithm is shown to converge provided that the preconditioner is a sufficiently accurate approximation of the inverse of the upper left block. Applications to the solution of steady-state Navier-Stokes equations are discussed, and, finally, the results of numerical experiments involving the algorithms are presented.


Using finite element method, we solve the heat conduction equation. In our calculation, we use 0.02 and 0.052 °C/year as temperature rising rate (Gt) in order to get the change of gas hydrate layer of Qinghai-Tibet Plateau (QTP) in global warming situation. Our calculation's major results are as follows: Our calculation demonstrates the gas hydrate layer's surface temperature is one of the major factors which influence the thickness of gas hydrate layer (TGH). When Gt=0.02 and 0.052°C/year, the changes of TGH are almost same. The lower the ground surface temperature (GST), the more change of TGH. Therefore we need to monitor the Qiangtang plateau which has low surface temperature and good organic material.


in their main contention, the facts now hidden or distorted may later become evident. As Professor Palmer's knowledge of the Indo-European community and its stratification depends on what, after all, is a laborious reconstruction out of the most diverse evidence, he is naturally led to follow the only course available and interpret the unknown through the known. The twist which this gives to the new data results, for instance, in imposing on the organisation of Mycenaean Greece the familiar features of the Germanic feudal system, which inevitably upsets established chronology. But Professor Palmer's enthusiasm for his subject is irrepressible and infectious: ' I venture (he says) to believe, too, that through the now open door of Nestor's archives room we can descry, at least in broad outline, the polity of the Indo-Europeans.' We share his faith, for he has scholarship and imagination, and, best of all, uses both with due modesty.


Semi-solid magnesium alloy slurry was produced by a newly self-developed mechanical stirring machine in order to prepare continuous semi-solid slurry. The changing principle of semi-solid microstructure was studied under different conditions—the changing of temperature, stirring rate, cooling rate and stirring time. It was showed that the lower the temperature of slurry, the higher the stirring rate, the longer the stirring time and the faster the cooling rate, the grain will be smaller and more evenly rounded. When the stirring speed and temperature are the same, better semi-solid spherical grains can be gained by increasing the stirring time. At the same stirring temperature and higher stirring speed, semi-solid spherical particles are smaller, rounder and more evenly; at a low stirring speed, we can't get ideal semi-solid spherical grains even if we increase the stirring time. The ideal technological parameters of semi-solid AZ61 alloy produced with no-dendritic structure were recommended to be 600°C~605°C (stirring end temperature) 、3min~ 5min(stirring time) and 500r/min(stirring rate). Compared with conventional casting alloy, semi-solid alloy mechanical properties were greatly improved. The non-dendrite semi-solid forming mechanism was studied; mechanical stirring semi-solid non-dendritic formation was the result of a variety of factors, the key cause is mechanical shear stress.


Logic Analysis Method (LAM) always was realized with some n-Figures binary numbers, its FM (Figures' Module) is the lowest in all FCN (Fixed Carrying Numbers), and all FCN are ones of special VCN (Variable Carrying Numbers). All Numbers' Value of VCN is very fuzzy, because their VCR (Variable Carrying Rules) may be designed in Artificial Intelligence (AI). FPGA is a new material Programmable Logic Units in end of the 20th century, it was with some properties such that, large memory of capacities, short delays of time, improvement able & flexibilities etc. On the basis theory of Neural Fuzzy System of Networks (NFSN), this paper gives a novel logic analysis method with AI-Fuzzy VCR. The dynamic logic analysis algorithm takes a reusing technique of VCR path, a process of middle-data to be shaped & placed in RAM. In the deep research & analysis of logic testing, this analysis method is still practicable.


Paleoceanographic and paleoenvironmental interpretations based on foraminifera, sedimentary data, radiocarbon dates, and stable isotope measurements were derived from two sections in the Skagerrak: a 115-m-thick Holocene marine section drilled onshore at Skagen near the northernmost tip of Jutland, Denmark, and a 9-m piston core from the Skagerrak, north of Skagen. The foraminiferal data show that arctic-subarctic environments in the deep Skagerrak-Kattegat area were succeeded by boreal conditions at 9.6 ka. This was a result of northward migration of the Atlantic polar front and inflow of warm Atlantic water into the area through the Norwegian Channel. A gradual warming of the water masses after 9.6 ka is indicated by the data. Rare foraminifera and high sedimentation rates are found between approximately 8.6 ka and 7.6 ka at both core locations. The modern foraminiferal assemblages of the area were fully established at 7.6 ka indicating that the modern circulation pattern in the Skagerrak-Kattegat after the opening of the English Channel and the Danish Straits was not established before this date. At 5.5 ka a sudden change to coarser sediments (higher-energy environments) and the appearance of the foraminifer Eoeponidella laesoeensis is recorded in the Skagen core. This indicates a rapid change in the hydrography reflecting altered meteorological and hydrographic conditions in the Skagerrak-Kattegat, including a strengthening of the Jutland Current and increased inflow of North Sea water into the Kattegat. The event is interpreted as a response to cooling at the end of the Holocene climatic optimum in late Atlantic time and possibly reflects a rapid cooling event of North Atlantic surface water masses.


The current researches were conducted to study humoral and cellular immunity in 118 major beta-thalassemia patients during various periods of time after splenectomy. Until the surgery the mentioned parameters of functional activities of segmented neutrophils in these patients were lower, since the second day, during a month after surgery the rates were gradually reducing, and during long date after splenectomy, these indices increased until baseline by the first year of the surgery and remained till the end of medical supervision. Thus, conducted researches showed that splenectomy renders oppressive influence upon the immune status of major beta-thalassemia patients, and all modified records of immunity recover and reach up to splenectomy level by the end of the first year after surgery.


This study investigated the duties, responsibilities, and attitudes of Parental Order Reporters (PORs) in surrogacy arrangements. A postal survey was distributed to all PORs employed by the Children and Family Court Advisory Support Service (Cafcass). A total of 32 PORs completed the questionnaire (response rate 44%). Just under half reported that they received assignments without sufficient help to complete them. They were generous in what they considered to be reasonable expenses to surrogates, but believed surrogates should not receive financial compensation (as a job). Although most PORs were positive about surrogacy, they had differential concerns about genetic and gestational arrangements and supported the child's rights to openness, including the identity of the surrogate and any half siblings. The majority of PORs believed there were some risks of possible exploitation by intended parents and considered these to be heightened on overseas arrangements. PORs also believed more should be done by the UK Government to prevent couples using surrogacy arrangements overseas. Results suggest that Cafcass should provide PORs with more help for this work. Further, policy makers and surrogacy agencies could be aware that most PORs believed there were some possibilities of exploitation of UK and overseas surrogates by intended parents.


Modern glass facades of the early and mid 20 century have always been synonymous with innovative and sophisticated building concepts. These building skins were often established as a feature reflecting international stylistic standards, enhancing the prestige of builders and occupants – although often independent from or even in contradiction with climatic requirements and local conditions. In particular, in Central Europe varying strategies for the revitalisation of modern glass walls, facades and windows have been developed and realised. Multi-storey and high-rise buildings from the 1950s and 1960s, such as Haus Hardenberg by Paul Schwebes (1955-56) and Europa-Centre by Helmut Hentrich and Huber Petschnigg (1965), both in Berlin, are typical facade constructions. The very diverse approaches of revitalisation of Haus Hardenberg and the Europa-Centre will serve as examples to be compared and described with regard to different planning and decision frameworks. Both buildings have passed through certain episodes of modification and revitalisation. Both are preserving their original appearance, but while the original facade construction of Haus Hardenberg has been maintained and modified, the single glass facade of the Europa-Centre has been totally changed into a double facade system. The architectural design, construction, functions and environmental qualities will be described and evaluated with regard to the original concepts and requirements. These buildings will be presented addressing their impact on the refurbishment of modern building skins in general and in relation to increasing energetic requirements. In this context newly developed steel profiles have been investigated to be used as an alternative for the revitalisation of protected facade constructions. The way in which Modern Movement buildings in other countries and continents can be adapted to climatic and socio-economic conditions will also be discussed.


Organizations are attempting to harness the power of big data analytics. Enterprise architecture can be used as an instrument to integrate big data analytics into the existing IT landscape and enabling the development of capabilities to create value from these technologies. Yet, there is limited research about the role of enterprise architecture in adopting big data analytics. This paper explores enterprise architecture roles and capabilities for the adoption of big data analytics by conducting a qualitative case study at the Dutch Tax and Customs Administration. The first attempt to adopt big data analytics was focused on integrating analytics into the current complex IT landscape, but this encountered many challenges and resulted in slow progress. To overcome these challenges, a separate department was created to quickly harness the potential of big data analytics. Enterprise architecture was used for impact analysis and to create a transition process. The findings suggest that enterprise architecture was used in different ways at the various stages of adoption and implementation, requiring different roles and a different set of capabilities. Enterprise architecture was found to be contingent on the type of technology and the situation at hand. We recommend more research into the role of the context in enterprise architecture research.


This paper presents a study of the blade pressure perturbation levels and the resulting blade forces in a high-pressure transonic turbine stage based on 3D time dependent viscous computations. Globally, the blade pressure unsteadiness is quantified with the RMS of the pressure perturbations integrated in both time and along the blade surface. Operation point as well as spanwise variations are addressed. Locally, the relative strength of the pressure perturbation events on the vane and rotor blade surface is investigated. To obtain information about the relative strength of events related to the blade passing frequency and higher harmonics, the pressure field is Fourier decomposed in time at different radial positions along the blade arc-length. The amplitude peaks are then related to the pressure events in space-time maps.With the help of the observations and results from the blade pressure study, the radial variations of the unsteady blade force and torque acting on a constant span blade profile section are investigated. The connection between the first and second vane passing frequency pressure amplitudes on the rotor blade surface and the resulting force and the torque amplitudes for three selected blade modes was investigated in detail. In this investigation the pressure was integrated over defined rotor blade regions to quantify local force contributions. Spanwise as well as operation point variations are addressed.© 2001 ASME


In general, the orbit-averaged radial magnetic drift of trapped particles in stellarators is non-zero due to the three-dimensional nature of the magnetic field. Stellarators in which the orbit-averaged radial magnetic drift vanishes are called omnigeneous, and they exhibit neoclassical transport levels comparable to those of axisymmetric tokamaks. However, the effect of deviations from omnigeneity cannot be neglected in practice, and it is more deleterious at small collisionalities. For sufficiently low collision frequencies (below the values that define the 1 / ν regime), the components of the drifts tangential to the flux surface become relevant. This article focuses on the study of such collisionality regimes in stellarators close to omnigeneity when the gradient of the non-omnigeneous perturbation is small. First, it is proven that closeness to omnigeneity is required to actually preserve radial locality in the drift-kinetic equation for collisionalities below the 1 / ν regime. Then, using the derived radially local equation, it is shown that neoclassical transport is determined by two layers located at different regions of phase space. One of the layers corresponds to the so-called ν regime and the other to the so-called superbanana-plateau regime. The importance of the superbanana-plateau layer for the calculation of the tangential electric field is emphasized, as well as the relevance of the latter for neoclassical transport in the collisionality regimes considered in this paper. In particular, the role of the tangential electric field is essential for the emergence of a new subregime of superbanana-plateau transport when the radial electric field is small. A formula for the ion energy flux that includes the ν regime and the superbanana-plateau regime is given. The energy flux scales with the square of the size of the deviation from omnigeneity. Finally, it is explained why below a certain collisionality value the formulation presented in this article ceases to be valid.


This report summarizes a recent study demonstrating simple and rapid synthesis of a new Al–Mg alloy system and ultimately synthesizing a metal matrix nanocomposite, which was achieved by processing stacked disks of the two dissimilar metals by conventional high-pressure torsion (HPT) processing. The synthesized Al–Mg alloy system exhibits exceptionally high hardness through rapid diffusion bonding and simultaneous nucleation of intermetallic phases with increased numbers of HPT turns through 20, and improved plasticity was demonstrated by increasing strain rate sensitivity in the alloy system after post-deformation annealing. An additional experiment demonstrated that the alternate stacking of high numbers of dissimilar metal disks may produce a faster metal mixture during HPT. Metal combinations of Al–Cu, Al–Fe, and Al–Ti were processed by the same HPT procedure from separate pure metals to examine the feasibility of the processing technique. The microstructural analysis confirmed the capability of HPT for the formation of heterostructures across the disk diameters in these processed alloy systems. The HPT processing demonstrates a considerable potential for the joining and bonding of dissimilar metals at room temperature and the expeditious fabrication of a wide range of new metal systems.


Abstract Chromium and molybdenum are intermediate elements of a periodic table group, both of which are both low but essential in nutrition because they play a key role in the metabolism of the chemical activity of the body. Anion analysis of these compounds in order to compare the properties of the elements of the periodic table in one The group is from the periodic table. In this paper, the quantum chemistry calculations related to the structural parameter of the two anions and the resulting complexes with glycine and alanine have been performed. The calculations have been done by HF and DFT methods and in the base series 6-31G *. NMR parameters and fixed tensors of coating and their changes have been considered. In this regard, the differences in the method in the accuracy of measurements have been considered.


This paper evaluates the capabilities of an integrated system level error detection technique using fault and error injection. This technique is comprised of two software level mechanisms for concurrent error detection, control flow checking using assertions (CCA) and data error checking using application specific data checks. Over 300,000 faults and errors were injected and the analysis of the results reveals that the CCA detects 95% of all the errors while the data checks are able to detect subtle errors that go undetected by the CCA technique. Latency measurements also shelved that the CCA technique is faster than the data checks in detecting the error. When both techniques were incorporated, the system was able to detect over 98% of all injected errors.


Abstract Essential oils (EOs) extracted from Lavandula luisieri and Cymbopogon citratus were tested for their antifungal activity against ten clinical isolates of dermatophytes isolated from cases of tinea pedis. Inhibition of conidial germination and antifungal drug/EO combination assay were tested on two ATCC reference strains of Trichophyton rubrum and Trichophyton mentagrophytes. EOs were characterised by high amount of oxygenated monoterpenes in their composition. Strong antifungal activity was observed for the majority of clinical strains, and fungicidal activity was demonstrated. Positive interaction between L. luisieri EO combined with terbinafine was observed against terbinafine-resistant strain (Tr ATCC MYA-4438). Significative reduction of the germination was observed above 100 μg mL−1. Both oils were safe to macrophage mammalian cells at tested concentration. This study describes the antifungal activity of L. luisieri and C. citratus EOs against dermatophytes, which could be useful in designing new formulations for topical treatments.


Prediction of the movement of water into subsurface excavations, and surrounding ground-water pressures, is of vital importance as regards the control of the stability and flooding of such excavations, especially below the general water table. As such it forms an important aspect of ground investigations for excavation works. Predictions are usually based on laboratory and in situ determinations of permeability along with observations of the ground-water levels in the area concerned.

Although established methods offer a means of assessing the results of permeability determinations, the actual ingress of water into excavations may depend on many factors. The objective of this paper is to consider the influence of geological controls, notably bedding planes and joints, on the permeability and ingress values in fractured rock masses. This is done with reference to tunnels and shafts excavated in Carboniferous Coal Measures strata as part of the Don Valley Intercepting Sewer Scheme in Sheffield, England.

The paper includes a consideration of the determination of permeability in fractured rock masses, the geological and hydrogeological situation of the excavations in question, the interpretation of in situ permeability tests in terms of the rock mass intactness and the prediction of rock mass permeability from these data.

A primary objective of the paper is to improve the quantitative prediction of water ingress into excavations using information that would usually be obtained in the course of a standard site investigation for a civil engineering structures. During the construction of the tunnels and shafts detailed records were kept of the ground conditions and the water ingress quantities. The variations in water ingresses are discussed in relation to the relevant hydrogeological and geological situation, including the presence of faulted and mine disturbed ground.


Given a high resolution compressed video stream this paper looks at the problem of extracting video from a small window at an arbitrary, but static location, in compressed form, without having to either decode the high resolution video stream or encode the window stream. Since state of the art video compression algorithms use motion compensation in one form or the other, the compressed video stream cannot be parsed to obtain the window stream without decoding the high resolution stream to some extent and subsequent re-encoding. On the other hand storing all possible windows as separate streams on the server is clearly infeasible, at least as of today, as it would lead to an explosion of the storage space requirement. It is shown that with a comparatively small increment in the server's storage requirement, it is possible to obtain compressed window streams out of the high resolution stream with minimal parsing, no decoding or re-encoding and little quality loss. Furthermore, methods to trade off the space required on the server with the compression efficiency of the window stream are shown. Experimental results obtained from applying the proposed method on MPEG-2 compressed video sequences are also provided.


Background
Takotsubo cardiomyopathy (TC) is a condition of transient left ventricular dysfunction precipitated by acute physical or emotional stress. The pathogenesis of TC is not well understood, but it is known to predominantly affect postmenopausal women in the context of physical or emotional triggers.

Aims
To describe a case of TC with an association to a never previously described work place stressor of bullying.

Case Report
A 48-year-old female lawyer developed acute chest pain after experiencing significant emotional distress at a workplace meeting. She had experienced 18 months of increasing work-related mental stress in a new managerial role. She was initially thought to have a non-ST-elevation myocardial infarction (NSTEMI) with widespread T wave inversion on electrocardiogram and elevated serial troponin. However, a diagnosis of TC was subsequently made given the characteristic apical ballooning morphology of the left ventricle found on echocardiogram, normal coronary arteries on angiography and a normal echocardiogram 3 weeks later. This case report describes TC in a younger demographic and a link with workplace bullying.

Conclusions
Chronic workplace bullying has the potential for serious physical harm by precipitating Takotsubo cardiomyopathy.


With increasing use of the Internet as a content-distribution platform, mere interoperability of the codec is no longer sufficient if content owners are not prepared to distribute their content online for fear of piracy. Therefore, one also needs interoperability in the area of managing and protecting related intellectual property rights. To provide interoperability of digital rights management (DRM) systems to protect the content rather than the distribution channel, MPEG has embarked on developing intellectual property management and protection (IPMP) specifications targeted at the content itself that are natively built into its standards. It is the hope that such standards will allow for interoperability of content commerce systems, giving consumers more choice, while providing rights holders with the tools to effectively protect their assets and to develop complex and attractive business offering to tempt consumers. While it remains uncertain whether standardization is in fact the right vehicle to provide the e-content market with an impetus to grow, it appears that MPEG is working on a set of specifications with relatively good chances of helping to achieve this goal.


Causal consistency (CC) is an attractive consistency model for geo-replicated data stores because it hits a sweet spot in the ease-of-programming versus performance trade-off. We present a new approach for implementing CC in geo-replicated data stores, which we call Optimistic Causal Consistency (OCC). OCC's main design goal is to maximize data freshness. The optimism in our approach lies in the fact that the updates replicated to a remote data center are made visible immediately, without checking if their causal dependencies have been received. Servers perform the dependency check needed to enforce CC only upon serving a client operation, rather than on receipt of a replicated data item as in existing systems. OCC offers a significant gain in data freshness, which is of crucial importance for various types of applications, such as real-time systems. OCC's potentially blocking behavior makes it vulnerable to network partitions. We therefore propose a recovery mechanism that allows an OCC system to fall back on a pessimistic protocol to continue operating during network partitions. We implement POCC, the first causally consistent geo-replicated multi-master key-value data store designed to maximize data freshness. We show that POCC improves data freshness, while offering comparable or better performance than its pessimistic counterparts.


Formants are the resonant frequencies of the vocal tract. As the vocal tract is moved to different positions to produce different sounds, there is a corresponding change in the formant frequencies. Estimates of formant frequencies for the lowest three formants can give important information about the phoneme produced. Change in the vocal tract position causes the formant frequency ranges to overlap. We investigate the ability of neural network classifiers to learn important distinctions between the formants, and to assign the appropriate formant labels. We used both spoken letters of the English alphabet and continuous speech. Our backpropagation network uses conjugate gradient optimization. We first experimently determined the best feature set, influenced by the features used by human labelers. Then we experimentally determined the best representation of those features, and network configuration. Representation questions include feature derivation, and absolute or relative indexing of location. Configuration questions include network size, and presentation and labeling of the feature vectors. We compare the performance to other published algorithms and human performance. This system also compares favorably to both.


Peripheral T- and natural killer (NK)-cell lymphomas (PTNKLs) are a heterogeneous group of lymphoid malignancies. We reclassified 142 cases and investigated their clinicopathologic features and outcome. Results showed that the most prevalent subtypes were extranodal NK/T-cell lymphoma, nasal type (eNK/T) (38.0%); angioimmunoblastic T-cell lymphoma (16.9%); and peripheral T-cell lymphoma, not otherwise specified (16.2%). Follow-up was available in 124 patients whose overall survival ranged from 3 days to 134 months, with a median of 11 months. Multivariate analysis demonstrated that thrombocytopenia (P = .001), elevated lactate dehydrogenase (P = .007), high Ki-67 index (P = .002), and T-bet expression in more than 20% of cells (P = .036) were independent factors for all cases-among which only the factor of T-bet indicated good outcome-and that thrombocytopenia (P = .011) and radiotherapy (P = .026) were significant for the eNK/T group. Thus, eNK/T was the commonest subtype in this series. The significance of T-bet in predicting outcome should be further confirmed.


The procedure for cathode design in electrochemical machining (ECM) is plagued by limited applicability, inaccuracy, and nonconvergence. So cathode design is a difficult problem must be faced and solved in ECM. We develop a new numerical approach for cathode design by employing a finite element method and this approach has been applied in the cathode design of aero-engine blades in ECM. The mathematic models of the electric filed and electrolyte flow filed distribution in EMC process are described primarily. Then the realization procedure of this approach is presented, in which the effects of electric filed and electrolyte flow filed distribution within the inter-electrode gap domain are concentrated. In order to verify the machining accuracy of the designed cathodes, the experiments are conducted using an industrial scale electrochemical machining system. The experimental results demonstrate that the machined blade have high surface quality and dimensional accuracy which proves the proposed approach for cathode design of aero-engine blades in ECM is applicable and valuable.


One of the challenges in the precise synthesis of giant surfactants lies in the homogenous functionalization of a head with bulky ligands. In this article, we report the use of thiol-Michael "click" chemistry as a facile, modular and robust approach to address this issue. A giant surfactant with acryloxyl-functionalized POSS (ACPOSS) head was conveniently constructed from commercially available acrylo POSS and polystyrene (PS). Functional thiols with different sizes, such as 2-mercaptoethanol, 1H,1H,2H,2H-perfluoro-1-decanethiol, 1-thio-β-D-glucose tetraacetate (sugar-SH), and 2-naphthalenethiol, were attached onto the head of the ACPOSS-PS conjugate by thiol-Michael and thiol–ene reactions. It was found that while both the methods offer a straightforward and highly efficient approach to prepare uniform and precise giant surfactants with small thiol ligands, only the former proceeds without apparent side reactions when large and bulky thiols, such as sugar-SH and 2-naphthalenethiol, are used. The former method also eliminates the need for UV irradiation or heat initiation. Therefore, the mild condition, high efficiency, and broad functional group tolerance of thiol-Michael chemistry should further expand the scope of POSS-based giant surfactants with unparalleled possibilities for head surface chemistry manipulation, which provides numerous opportunities for nanofabrication by the direct self-assembly of giant surfactants.


The standard procedure for blood glucose measurements is enzymatic testing. This method is cheap, but requires small samples of open blood with direct contact to the test medium. In principle, NMR provides non-contact analysis of body fluids, but high-field spectrometers are expensive and cannot be easily utilized under clinical conditions. Low-field NMR systems with permanent magnets are becoming increasingly smaller and more affordable. The studies presented here aim at exploring the capabilities of low-field NMR for measuring glucose concentrations in whole blood. For this purpose, a modern 1 T benchtop NMR spectrometer was used. Challenges arise from broad spectral lines, the glucose peak locations close to the water signal, low SNR and the interference with signals from other blood components. Whole blood as a sample comprises even more boundary conditions: crucial for reliable results are avoiding the separation of plasma and cells by gravitation and reliable reference values. First, the accuracy of glucose levels measured by NMR was tested using aqueous glucose solutions and commercially available bovine plasma. Then, 117 blood samples from oral glucose tolerance testing were measured with minimal preparation by simple pulse-acquire NMR experiments. The analysis itself is the key to achieve high precision, so several approaches were investigated: peak integration, orthogonal projection to latent structure analysis and support vector machine regression. Correlations between results from the NMR spectra and the routine laboratory automated analyzer revealed an RMSE of 7.90 mg/dL for the best model. 91.5% of the model output lies within the limits of the German Medical Association guidelines, which require the glucose measurement to be within 11% of the reference method. It is concluded that spectral quantification of glucose in whole blood samples by high-quality NMR spectrometers operating at 1 T is feasible with sufficient accuracy.


ABSTRACT Macrophages encode several Toll-like receptors (TLRs) that recognize bacterial components, such as lipoproteins (TLR2) or lipopolysaccharides (TLR4), and activate multiple signaling pathways. Activation of transcription factor NF-κB by TLR2 or TLR4 signaling promotes proinflammatory and cell survival responses. Alternatively, TLR2 or TLR4 signaling can promote apoptosis if the activation of NF-κB is blocked. The gram-negative bacterial pathogen Yersinia pseudotuberculosis secretes into macrophages a protease (YopJ) that inhibits the activation of NF-κB and promotes apoptosis. We show that primary macrophages expressing constitutively active inhibitor κB kinase β (IKKβ) are completely resistant to YopJ-dependent apoptosis, indicating that YopJ inhibits signaling upstream of IKKβ. Apoptosis is reduced two- to threefold in TLR4−/− macrophages infected with Y. pseudotuberculosis, while the apoptotic response of TLR2−/− macrophages to Y. pseudotuberculosis infection is equivalent to that of wild-type macrophages. Therefore, TLR4 is the primary source of apoptotic signaling in Yersinia-infected macrophages. Our results also show that a small percentage of macrophages can die as a result of an apoptotic process that is YopJ dependent but does not require TLR2 or TLR4 signaling.


Induction motor is an important system component in integrated electrical vehicle working on different operating conditions. Due to these operations, robustness and performance of the control interfaces should be taken into account in the motor design. In this paper, we apply a new architecture for a fault tolerant control using Youla parameterization for an induction motor. The distinguished feature of proposed controller architecture is that it shows structurally how the controller design for performance and robustness may be done separately which has the potential to overcome the conflict between performance and robustness in the traditional feedback framework. A fault tolerant control architecture includes two parts: one part for performance and the other part for robustness. The controller design works in such a way that the feedback speed control of the induction motor will be solely controlled by the proportional integral PI performance controller for a nominal model without disturbances and H∞ robustification controller will only be activated in the presence of the uncertainties or an external disturbances. The simulation results demonstrate the effectiveness of the proposed fault tolerant control architecture.


Modern science clearly demands for a higher level of reproducibility and collaboration. To make research fully reproducible one has to take care of several aspects: research protocol description, data access, environment preservation, workflow pipeline, and analysis script preservation. Version control systems like git help with the workflow and analysis scripts part. Virtualization techniques like Docker or Vagrant can help deal with environments. Jupyter notebooks are a powerful platform for conducting research in a collaborative manner. We present project Everware that seamlessly integrates git repository management systems such as Github or Gitlab, Docker and Jupyter helping with a) sharing results of real research and b) boosts education activities. With the help of Everware one can not only share the final artifacts of research but all the depth of the research process. This been shown to be extremely helpful during organization of several data analysis hackathons and machine learning schools. Using Everware participants could start from an existing solution instead of starting from scratch. They could start contributing immediately. Everware allows its users to make use of their own computational resources to run the workflows they are interested in, which leads to higher scalability of the toolkit.


This paper studies the market microstructure of pre-industrial Europe. In particular we investigate the institution of the broker in markets and fairs, and develop a unique data set of approximately 1100 sets of brokerage rules in 42 merchant towns in Central and Western Europe from the late 13th to the end of the 17th century. We show that towns implemented brokerage as an efficient matchmaking institution in a two-sided market problem. Furthermore, towns differentiated seller-friendly from buyer-friendlier matching mechanisms. We show that the decision to implement matchmaking mechanisms, and whether these mechanisms would be buyer- or seller friendly, depends on the products in question and the stated policy goals of the town, as well as time and geographic variables.


Mediterranean regions are projected to experience more frequent, prolonged and severe drought as a consequence of climate change. We used a retractable rainfall shelter, to investigate the impact of extreme droughts on the development of Quercus ilex leaves, flowers and fruit. In 2008, 97% of rainfall was excluded from a forest plot during the autumn, representing 50% of the 1127 mm of rain that fell during the year. In 2009, 87% of rainfall was excluded during the spring, representing 58% of the 749 mm that fell during the year. The rainfall shelter did not impact neither incident radiation nor air temperature. Autumn rainfall exclusion did not significantly affect leaf, flowers or fruit development. Spring rainfall exclusion resulted in larger and more sustained depression of leaf water potential during the key phases of foliar and floral development. Consequently, only half of the sampled trees (6) reached the shoot lengthening stage which leads to functionally mature leaves (phenophase 4), with one abandoning leaf development at budburst (phenophase 3) and the other two at the bud swelling stage (phenophase 2). All trees of the control plot passed phenophase 4, with most reaching complete leaf development. The impact of extreme droughts on flower development differed between the sexes. The spring exclusion had no effect on male flower, but only one of six trees completed female fruit maturation, compared with four in the control plot. The difference between the male and female drought impacts is likely attributable to the occurrence of male floral development before the period of lowest leaf water potential, and to the lower resource allocation requirements of male flowers. The information provided by our experimental approach may constitute a crucial step to evaluate the impact of increasing drought due to climate change on the most dominant Mediterranean tree species and to help drawing a full picture of the ecological consequences of the decline in water resource on forest dynamics under changing conditions.


October 2015 Water-sector development is inevitably based on changes in people's behaviour. We analyse why some types of domestic water-use behaviours change more easily than others. Our case study is a water supply and sanitation intervention in remote and rural Nepal. We found that collective opportunities, degree of individual freedom, and individual incentives influenced the ease of the promoted behaviour changes. The enhanced individual opportunities, incentives, and collective tolerance enabled behaviour changes that were regarded as beneficial by the people themselves, whereas the existing social traditions in our case-study context often restricted those changes. Often, the individual agency and the collective traditions confronted one another. We suggest that this study can provide a design for predicting possible opportunities and challenges regarding behaviour changes in field operations, and for enhancing joint operation of individual and collective capabilities at local levels in the development intervention context.


This paper gives the results obtained for the phase II, Task B2 Round Robinorganised by the CEA Saclay within the ESIS (European Structural Integrity Society),Technical Committee 8 on Numerical Methods. It is part of a larger project initiated in1993 and organised in 3 phases. Phase I was focussed on the determination of localapproach parameters for ductile tearing (Task A) and for cleavage (Task B) for a Germanpressure vessel steel. The objective of Phase II was to perform finite element simulation ofcrack growth CT for ductile tearing (Task A) and for cleavage (Task B). For this latterTask, the objective was to compute the toughness and the failure probability of a CTspecimen on the lower shelf at –154°C for the 22 NiMoCr 3 7 German RPV steel. Elevenlaboratories have contributed to this Round Robin and six different FE codes have beenused.


The fine collection of Oolitic fossils which was made by the late Mr. William Walton, of Bath, and was purchased some years ago by the University of Cambridge, contains a very remarkable series of specimens of a Crinoid from the Great oolite of Lansdown, a well-known hill at Bath. Its occurrence seems to have been first recorded (though not first noted) in the year 1828 by the late Dr. J.E. Gray, who made a curious error with regard to this geological horizon, stating it to have been found in the Lias. He named the type Apiocrinites Prattii, and described it as intermediate in character between the A. ellipticus and A. rotundus of Miller. Some years after the publication (1821) of the well-known work on Crinoids by the last-named author, some specimens of this species were shown to him by the Rev. H. Jelly, who states that Miller "was unable to satisfy his own mind as to their true nature and history." in the year 1833 a semipopular illustrated account of these fossils was published by Mr. Jelly, and about the same time they were redescribed by Goldfuss, with the aid of some excellent figures, under the name of A. obconicus. he had, however , smaller series of specimens than those at Jelly's disposal, some of which now form part of the Walton collection; and the great peculiarity of the type, viz. the very variable length of the stem, which had been previously noted by Jelly, did not attract his attention.


The pharmacokinetics of salicylate after a single oral solution dose of 600 mg of sodium salicylate were investigated in 22 male subjects. Subjects were healthy nonsmokers and were not taking any regular medication. The plasma concentration and urinary excretion of salicylic acid and its metabolite, salicyluric acid, as well as the urinary excretion of salicyl glucuronides were determined. Urinary recovery essentially accounted for the administered dose and was not influenced by age, nor was the apparent oral clearance of salicylic acid. Assuming no presystemic elimination, it could be concluded that systemic availability is unaffected by age. An increase in the apparent volume of distribution, Varea, and a decrease in the maximum plasma salicylic acid concentration with age were observed. Renal clearance of salicyluric acid decreased significantly with age and was found to correlate significantly with creatinine clearance. The authors conclude that age does not have a major influence on salicylate disposition in healthy adult men.


Nociceptin (NC) and the opioid receptor like-1 receptors are widely distributed in areas of the neuraxis that are part of the descending modulatory pain system. We used the tail-flick assay in mice to assess the interaction between NC and other analgesic compounds acting on different areas of the descending pathway. Given by intracerebroventricular injection, NC induced hyperalgesia at 10 nmol (39% of reduction vs. control group). The same dose of NC reversed analgesia induced by distinct classes of analgesia-producing compounds such as morphine, dynorphin A or baclofen. NC caused a reduction of their antinociceptive effects: 61, 41 and 27%, respectively. Thus, NC at the supraspinal level appears to interact with both opioid and gamma-aminobutyric acid(B) systems producing anti-analgesic effects probably through the descending pathway for pain control.


The electric quadrupole transition γ-ray energies and the dynamical moments of inertia of the five superdeformed (SD) bands of 150Gd have been investigated with a four parameter approach inspired of the interacting boson model. The calculated results agree with experimental data well. It indicates that the four parameter approach is powerful in describing both the yrast SD band and the excited SD bands of even-even nucleus no matter whether the bands are built upon some extra single particle excitations.


Abstract : Results of long-term studies on rats and rabbits, injected intratracheally with well-characterized key samples of beryllium oxide prepared by calcining beryllium hydroxide for 10 hours at 500, 1100 and 1600 C, respectively, show clearly that there is a definite gradation in biological response depending upon the oxide administered. Thus, the oxide calcined at 500 C was highly active as judged by histopathological examination of the lungs, incidence of tumors, and translocation of beryllium from the lungs to other tissues. In contrast, the oxide calcined at 1600 C showed only minimal effects. Dose-response studies were carried out, using carefully prepared subsamples of 'respirable particle size' (1 to 5 microns) of the three key oxides; results showed a definite gradation in response which diminishes with decreasing dosages of the administered oxide. Investigations on motor exhaust products show that some samples have chemical, physical, and toxicological properties similar to the beryllium oxide calcined at 1600 C. On the other hand, other samples are heterogeneous, contain considerable quantities of water-soluble beryllium, and vary in toxicity. The mechanism of toxic action of beryllium oxide was investigated through study of chemical and physical properties, solubility and adsorption studies, serum electrophoretic analyses, and immunological experiments. Suggestions are made for further studies. (Author)


The coordination for agro-food chains is an issue of a large interest in Romania, where agricultural structures are atomized and produce mostly for self-consumption. Cooperation and integration, like coordination mechanisms, must be reconsidered in chains' efficiency terms. In this paper the are given models' proposals of agro-food chains coordination in Romania.


"Music and Talent" is an educational project for children between 3 and 9 years old. The aim of the project is to use music and musical intelligence as resources for enhancing important skills in social and cognitive development. These skills are self-esteem, self-confidence, motivation, social and emotional relationships, and well-being. The first part of the article describes the project's foundation, organization and developed activities. The second part of the article presents the results of two exploratory studies that have been carried out to evaluate some of the developed activities. Study 1 measured the impact of an active music language learning methodology on the "originality" dimension of creativity. A quasi-experimental design was adopted, with experimental and control groups tested pre and post the musical intervention. Findings show a statistically significant increase in the originality dimension in the experimental group. Study 2 measured the children's self-efficacy in relation to their participation in the Music and Talent project, with positive results. An exploratory study was adopted as the research design, using a validated 10 steps Likert questionnaire with 15 items.


Building's design is developing to involve complexities of engineering systems, where design process requires various disciplines of participants to solve the complex issues. Collaborative design is developed with main purpose to facilitate the integration of multiple participants in design process to produce best design. This paper presents conceptual understanding, current practices, and theoretical framework of collaborative design. Literature review builds the conceptual understanding, exploratory study through indepth interviews to design managers and designers reveals the current practices, and grounded theory constructs the theoretical framework. The review had found three main indicators of collaborative design, and through those indicators it has been identified that collaborative design is implemented at design process. The interviews had revealed that best design is hard to be achieved although collaborative design has been applied. Through grounded theory analysis, it has been found that the lack understanding of Knowledge Management (KM) roles is found to be main issue collaborative design practices.


The diagnosis of restless legs syndrome is made on the basis of the clinical symptoms and, if applicable, complemented with a polysomnography.This is followed by neurophysiological examinations and laboratory diagnostics and permits a differentiation between idiopathic and secondary RLS. The therapy depends upon the form and severity of the disease. For secondary RLS, the primary disease must be treated or the symptom-inducing medication must be discontinued. An idiopathic RLS is treated with drugs. Primarily, L-dopa/benserazide and dopaminergic agonists are used, but opioids and anticonvulsants are also successful.


In a healthy democracy, one would expect to see roughly equal levels of political participation among men and women. Yet—aside from voting—women are significantly less politically engaged than men at both the mass and elite levels (Atkeson 2003; Bennett and Bennett 1989; Burns, Schlozman, and Verba 2001; Lawless and Fox 2010; Verba, Burns, and Schlozman 1997). The political engagement gender gap suggests that some form of "adverse selection" is at play in the system (Mansbridge 1999, 632). This takes many forms: women have traditionally had less access to resources, more burdensome family obligations, and fewer relevant role models. However, emerging research demonstrates that even when accounting for many of these factors, women remain less engaged with politics than similarly situated men. This suggests that changing these structural factors is not enough to close the gender gap in political engagement—we must address the "gendered psyche" that prevents many women from fully participating in civic life (Lawless and Fox 2010, 12).


SP ABSTRACT This study evaluated how changing the structure of Brachiaria brizantha cv. Marandu pasture under different forage allowances (FA) of 4, 7, 10 and 13kg DM/100kg BW (body weight) affected animal behavior over a two-year evaluation period. The experiment was conducted as a randomized block design with three replications (paddock). Sward height, total forage, and stem mass were lower for pastures managed with lower FA. Lower leaf mass was observed for lower FA in the second year. In hand-plucked samples, leaf and stem percentages remained unchanged in the morning but leaf percentage increased while stems decreased in the afternoon. Permanence time decreased linearly with increasing FA. In turn, a quadratic effect was observed for displacement rate. The bite rate was similar among different FAs. The results demonstrate that FA varying between 7 and 10kg DM/100kg BW are more suitable to balance the amounts of leaves and stems in the sward. The studied FA levels do not limit forage availability. Permanence time decreases and displacement rate increases as FA


Postmortem toxicological results for neonates and stillborn fetuses were examined to determine the incidence of drug exposure in utero and the relationship to fetal mortality. From 15,600 fatalities with toxicological analyses, 39 subjects were identified; 22 had positive findings (56%). Among the general population, 10,500 had positive findings (67%). Among the subject population, 22 drugs/metabolites were identified; cocaine/benzoylecgonine was most frequent (9 of 22 cases, 41%) then methamphetamine/amphetamine (7 of 22 cases, 32%). Respective incidences among the general positive population were 12% and 6%. Fetal/neonatal concentrations overlap the general population and exceed the mother. Remaining substances, detected largely in fatalities unrelated to drug exposure, were of little toxicological significance. The variety, with exceptions, reflects the general population. That the incidence of cocaine and methamphetamine among fetuses/neonates is three‐ and fivefold greater than the general population is evidence that maternal abuse of these drugs poses greater risk to fetal viability than all other substances identified.


A THESIS ON A 3D INPUT DEVICE FOR SKETCHING CHARACTERS by Mark A. Schroering ADVISOR: Professor C. Grimm May, 2003 Saint Louis, Missouri The goal of this project is to develop a 3D input device using a stiff piece of paper and a camera. The camera tracks the piece of paper in 3D space. The user orients the paper in 3D space and then draws on the paper using a pen-like device. The camera tracks the movement of the pen on the piece of paper. The location of the pen in 3D space can then be calculated from the orientation of the paper. A drawing application that uses this 3D input device was also developed. The application allows a user to make characters by sketching ellipses. The drawing application creates a virtual rendering of the paper and displays this to the user. As the user positions the real paper, the virtual one mirrors its movements. The user can draw shapes on the paper. These shapes then get rendered in the virtual scene.


The influence of the negative spillover effect on the different strategies of sales promotion was studied by game theory in dual-channel under Internet environment. The equilibrium results of uniform strategy and non-uniform strategy were analyzed and compared with the integrated decision mode according to the difference of strategies. Combined with the numerical example, the analytical results show that: The wholesale price of the manufacturer was increasing with the negative spillover effect coefficient under the uniform strategy; The proportion of the revenue sharing was decreasing under the inconsistent strategy; The profit and the sales promotion effort of both parties and the profit of the whole supply chain were decreasing under different strategies; The non-uniform strategy was superior to the consistent strategy for the manufacturer and the whole supply chain; The uniform strategy was superior to the non-uniform strategy for the retailer.


This study aimed to investigate the relationship between air pollutant exposure, i.e., Particulate Matter (PM2,5), and the numbers of airborne bacterial colonies inside the classroom to the respiratory symptoms of three primary school children in West Jakarta.

 We did a quantitative study with a cross-sectional design using variables, i.e., age, sex, physical activity, nutritional status, students' density, ventilation, classroom temperature, and classroom humidity. We used Haz-Dust EPAM 5000 to measure PM2,5,MAS 100 NT to calculate the total bacterial colony, spirometry to measure the respiratory capacity, and questionnaire to measure other related variables.

 We found a significant relationship between PM2,5concentration with respiratory symptoms, however, there was no significant relationship between the total number of airborne bacterial colonies with respiratory symptoms.

 Based on our results, we conclude that there was a significant relationship between the PM

 2,5

 concentration and obstructive pulmonary symptoms and there was no significant relationship between the numbers of the bacterial colonies with pulmonary symptoms.


This basic qualitative study examines the parental investment strategies of first-generation African American rural college graduates in cultivating college student success. Extant literature has demonstrated that the role of the family is necessary to support the college student and that the investment of the parent is paramount to student college completion. Although educational attainment is an important goal for African American rural residents, research detailing strategies that cultivated student college completion among this population is needed to fill the gaps in the literature. The objectives were to discuss communication, involvement, and factors of influence to determine how these parents transferred their educational beliefs to their children and supported them through college graduation. These stories of success were told through the eyes of first-generation parents and their second-generation adult offspring.

Research detailing the parental investment strategies toward college completion is necessary to inform parents, educational institutions, and rural college student completion in postsecondary institutions of the strategies necessary to ensure college success in this population. Lieberman?s transgenerational theory, along with concepts extracted from parental investment as it relates to education, provided the conceptual lens for the study. Data collected through interviews and documents were analyzed utilizing content analysis. Ten semistructured interviews were conducted with parents and their adult offspring. Interviews gleaned the lived experiences of the participants. Data analysis revealed six themes: (a) Catch Them Early, (b) Set the Tone, (c) Keep Them Busy, (d) Don?t Let Them ?Break Rank,? (e) Encourage Advancement, and (f) Tell the Generations. The findings support the importance of developing a family investment team, how a return on parental investment occurs, making use of rural extracurricular programming, and transferring positive beliefs regarding higher education.


The gas-liquid-solid fluidized bed has emerged in recent years as one of the most promising devices for three-phase operation. Such a device is of considerable industrial importance as evident from its wide application in chemical, refining, petrochemical, biochemical processing, pharmaceutical and food industries. Selection and design is one of the main parameter in the performance of three phase system. Success is dependent on the effective contact between the phases. Even though a large number of experimental studies have been done in different process parameters and physical properties, the complex hydrodynamics of three phase fluidized bed reactors are not well understood due to complicated phenomena such as particle–particle, liquid–particle and particle–bubble interactions. For this reason, computational fluid dynamics (CFD) has been promoted as a useful tool for understanding multiphase reactors for precise design and scale up. In the present work three different configuration of cylindrical column has been taken for studying co-current gas-liquid-solid fluidization with the help of commercial CFD codes as FLUENT. The main focus for analyzing the results is on the column with 1.88 m height and diameter of 0.1 m containing solid particles as glass beads of size 2.18 mm and 4.05 mm. In the present study of three phase fluidized simulation the hydrodynamic parameters investigated includes phase hold up, velocity profiles of all phases, bed expansion, bed voidage, static pressure drop, frictional pressure drop at wall, and energy flows. The operating variables varied includes liquid and air inlet velocity, initial solid static bed height and particle size. The dynamic characteristics obtained from CFD simulation have been validated with the experimental results and a good agreement has been observed. Eulerian-Eulerian granular multiphase flow approach is capable of predicting the overall performance of gas–liquid–solid fluidized bed. The expanded bed height is strong function of liquid velocity, it increases with liquid velocity. Velocity of the phases has been observed more in center region than near at wall in fluidized bed. Bed voidage increases with the liquid velocity and depending on the particle size. Axial velocity in small diameter column is more than the large diameter column. Frictional pressure drop at wall has been found to decrease with increase in the bed height.


Repetitive transcranial magnetic stimulation (rTMS) has shown variable effect on tinnitus. A prospective, randomized 6-month follow-up study on parallel groups was conducted to compare the effects of neuronavigated rTMS to non-navigated rTMS in chronic tinnitus. Forty patients (20 men, 20 women), mean age of 52.9 years (standard deviation [SD] = 11.7), with a mean tinnitus duration of 5.8 years (SD = 3.2) and a mean tinnitus intensity of 62.2/100 (SD = 12.8) on Visual Analog Scale (VAS 0–100) participated. Patients received 10 sessions of 1-Hz rTMS to the left temporal area overlying auditory cortex with or without neuronavigation. The main outcome measures were VAS scores for tinnitus intensity, annoyance, and distress, and Tinnitus Handicap Inventory (THI) immediately and at 1, 3, and 6 months after treatment. The mean tinnitus intensity (hierarchical linear mixed model: F3 = 7.34, p = .0006), annoyance (F3 = 4.45, p = .0093), distress (F3 = 5.04, p = .0051), and THI scores (F4 = 17.30, p < .0001) decreased in both groups with non-significant differences between the groups, except for tinnitus intensity (F3 = 2.96, p = .0451) favoring the non-navigated rTMS. Reduction in THI scores persisted for up to 6 months in both groups. Cohen's d for tinnitus intensity ranged between 0.33 and 0.47 in navigated rTMS and between 0.55 and 1.07 in non-navigated rTMS. The responder rates for VAS or THI ranged between 35% and 85% with no differences between groups (p = .054–1.0). In conclusion, rTMS was effective for chronic tinnitus, but the method of coil localization was not a critical factor for the treatment outcome.


This chapter examines how next-generation visual social platforms motivate students to capture authentic evidence of their learning and achievements, publish digital artifacts, and share content across visual social media. Educators are facing the immediate task of integrating social media into their current practice to meet the needs of the twenty-first century learner. Using a case study, this chapter highlights through empirical work how nascent visual social media platforms such as Pinterest are being utilized in the college classroom and concludes with projections on ways visual networking platforms will transform traditional models of education.


The Great Plains has experienced population loss for most of the 20th century while the Rocky Mountain region has experienced rapid population growth in the past few decades. This paper examines net migration by county for Montana between 1995 and 2000 disaggregated by age and educational level. Montana was chosen because it straddles the Great Plains and Rocky Mountain regions and thus provides an opportunity to compare and contrast net migration and population change in two regions undergoing fundamentally different population processes. Regression analysis was applied to determine the predictor variables responsible for net migration between 1995 and 2000. Dependent variables concerned economic, demographic, and environmental characteristics of each of the counties. Overall, median household income and the Rocky Mountains explained the greatest amount of variance in the dependent variables, suggesting that both economics and the environment play a role in migration patterns in Montana.


Sperm cryopreservation and increasingly oocyte cryopreservation are common forms of fertility preservation for oncology patients facing gonadotoxic therapy. Both procedures present challenging ethical issues with regard to informed consent, given that the context for these procedures is a disease that carries a significant risk of mortality. We argue that the current consent process does not allow for adequate collection of information about a patient's wishes for the custody of cryopreserved gametes in the case of premature death. After review of the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine guidelines we propose that a new, comprehensive consent procedure for sperm and oocyte cryopreservation including a 'roll-down' option is imperative to protect the autonomy of these oncology patients. This 'roll-down' option should allow for the transfer of custody of gametes to a pre-selected alternative recipient(s) if the original recipient no longer intends to use the gametes to create a child. We also demonstrate that objections over non-spousal custody of gametes can be overcome with sound ethical arguments.


On Palawan Island, Philippines, known for its high biodiversity and dynamic environmental movement, development, participation, and conservation have been enveloped by the twin discourses of environmentalism and sustainable development. This essay considers environmental policy on Palawan and several case studies of sustainable development projects that emphasize community-based resource management (CBRM). Recent critiques suggest that CBRM has not been successful because communities lack self-sufficiency and claims of "local participation" are merely rhetorical. We argue that analyses of CBRM should consider three aspects of Philippine environmentalism: whether rhetoric regarding resource management matches reality in the eyes of local residents; the overlapping roles of government and nongovernmental organizations (NGOs); and multiplex relationships of NGOs with local communities. Our findings suggest that despite some difficulties, stronger NGO roles in CBRM have generally resulted in better environmental protection, and through relationships with NGOs, communities in the Philippines can indeed take action to serve their own best interests.


Hindsight allows present-day scholars to view the development of academic disciplines in a light that contemporaries would never have seen. Hence, from our perspective, Mary Furner's assertion that anthropology developed as a profession reacting against biology and the physical sciences makes sense, for we tend to celebrate the triumph of cultural anthropology as the coming of age of the discipline. However, this trajectory of professional development was not a necessary or predestined development. Rather, the eventual (if occasionally still embattled) predominance of culture over the categories of race, nation, and biology was only one of many possible outcomes. This paper investigates a different trajectory, one that most current scholars would hope has been relegated to the dustbin of history. It is still a cautionary tale, though, in that while the racial anthropology followed in this narrative did not survive World War II, its practitioners did enjoy a degree of prominence and influence that was much greater and longer than has been generally acknowledged by current accounts.


We propose a reconstruction technique which consists in defining a parametric surface lying on a closed curve by setting the extremal behavior of the surface along the curve on which it lies. Therefore, we most build a set of curves in space from a stereo reconstruction of matched and closed contours in an image pair. Then, we use photometric information extracted near the image contours to define the local behavior of the surfaces lying on the closed curves. In order to build such a surface we use the duality existing between a stereo-based reconstruction which is able to determine the position of points in the scene space and photoclinometry which gives information about the shape of the objects in the scene. Our geometric model is composed of a radial set of triparametric Gregory patches for each surface to reconstruct. The topological concepts introduced by these kind of surfaces and the use of photometric models gave a framework for both image analysis processing and reconstruction geometrical processing.


This thesis describes the search for genetic variants of the human apolipoprotein B (apoB) gene that have the potential to affect serum lipid levels. ApoB has a central role in lipid metabolism, both in maintaining the structure of the LDL particle and acting as the ligand for the LDL-receptor. The apoB gene is a candidate gene for the development of coronary artery disease. Eight patients whose LDL had reduced binding to the LDL-receptor were screened for mutations in the gene region encoding the putative receptor binding domain (residues 3130 to 3630). None were found, and it was concluded that other regions of the apoB protein may also be involved in forming the ligand for the LDL-receptor. There is some evidence that regions of apoB encoded by exon 29 of the gene may also affect binding of LDL to the receptor and so this exon was also screened for variations. A common polymorphism was discovered in exon 29 of the gene which results in the substitution of serine for asparagine at residue 4311 of the mature protein. In population samples from four different ethnic groups this polymorphism is in complete linkage disequilibrium with a reported polymorphism in exon 26 of the same gene. In addition, these two polymorphisms show complete association with the Antigen group (x/y) protein polymorphism of apoB and thus these amino acid substitutions are candidates for being the molecular bases of the Ag(x/y) epitopes. In a sample of healthy Swedish males there was a trend for the allele encoding Leu2712, Ser4311 and Ag(x) to be associated with reduced mean serum levels of apoB and LDL-cholesterol and raised levels of HDL-cholesterol, although only the latter reached statistical significance in the population sample studied. The high degree of linkage disequilibrium existing across the entire apoB gene enabled a phylogenetic tree for the human apoB gene to be postulated. This parsimonious model assumed that each haplotype in the tree was derived from the preceding one by single base substitutions and one small deletion without obligate recombination events. The validity of this model was tested in a sample of Swedish myocardial infarction patients and age-matched controls. All the postulated haplotypes were seen unequivocally, however other rare, unpredicted haplotypes were also present and these occurred significantly more frequently in the patient than in the control group. Recombination events could explain the generation of the unpredicted haplotypes. Two of the unpredicted haplotypes, uniquely defined by the presence of the XbaI X-allele in combination with the allele encoding Ag(a), were seen unequivocally and were found to be associated with raised mean serum apoB levels. This reached statistical significance in the patient group. A search was made for other amino acid substitutions encoded by exon 29 of the apoB gene in a group of individuals with aberrant binding of LDL to the receptor. Only one was found, this resulted in the substitution of threonine for arginine at residue 4243 of mature apoB. The entire exon 29 of the human apoB gene was cloned and expressed in a baculovirus expression system. A peptide of approximately 60kDa was detected using the antibody Bsol16 on a western blot. This expressed peptide has the potential to be used to test whether the apoB region encoded by exon 29 has affinity for lipid and the LDL-receptor.


The data on the value of pharmacokinetic parameters and pharmacologic properties of antibiotics for the development of optimal regimens of antibacterial therapy are presented. The impact of various symptoms and syndromes of purulent septic processes (uremia, anemia, obesity or hyperbilirubinemia) on antibiotic pharmacokinetics is discussed. Approaches to the improvement of schemes for antibiotic therapy of various pathological conditions are noted. Procedures (a microbiological one and those with the use of apparatus) for the determination of antibiotic concentrations in serum and tissues are described. Factors useful for the development of individual regimens of antibiotic therapy of various nosologic forms of infectious inflammatory diseases are indicated: some indices characterizing susceptibility of the pathogen to the drug used (minimum antibacterial, minimum inhibitory and bactericidal concentrations), difficulties with their interpretation (the phenomena of the pathogen persistence, microbial tolerance and Eagle's effect), environmental influences in the infection foci on the drug concentration.


Endocrinopathies in patients with hypocalcemia and hyperphosphatemia that share resistance to parathyroid hormone (PTH) are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia (PHP-Ia) often present with additional hormonal resistance and show characteristic physical features that are jointly termed as having an Albright's hereditary osteodystrophy (AHO) phenotype. Alternatively, PHPIb patients predominantly have PTH and sometimes TSH resistance but do not present with AHO features. Most of these PHP forms are caused by defects in GNAS, an imprinted gene locus consisting of maternal, paternal and biallelic transcripts. PHP-Ia is caused by heterozygous inactivating mutations in those exons of GNAS encoding the alpha subunit of the stimulatory guanine nucleotide-binding protein (Gsalpha) while PHPIb results from epigenetic GNAS defects. Familial and sporadic forms of PHP-Ib have distinct GNAS imprinting patterns: familial PHP-Ib patients have an exon A/B-only imprinting defect whereas sporadic PHP-Ib cases have abnormal imprinting of the three differentially methylated regions (DMRs) in GNAS. This classification of PHP was made years ago but was recently questioned since different studies showed GNAS epigenetic defects in PHP-Ia patients. In this review, we focus on the epigenetic description and screening methods of GNAS, the associated pathology and the recent need for a PHP reclassification.


Objectives. To identify reasons for inclusion of international practice experiences in pharmacy curricula and to understand the related structure, benefits, and challenges related to the programs. Methods. A convenience sample of 20 colleges and schools of pharmacy in the United States with international pharmacy education programs was used. Telephone interviews were conducted by 2 study investigators. Results. University values and strategic planning were among key driving forces in the development of programs. Global awareness and cultural competency requirements added impetus to program development. Participants' advice for creating an international practice experience program included an emphasis on the value of working with university health professions programs and established travel programs. Conclusion. Despite challenges, colleges and schools of pharmacy value the importance of international pharmacy education for pharmacy students as it increases global awareness of health needs and cultural competencies.


The purpose of this study was to explore what constitutes an expert registered nurse in a labour and delivery unit. A qualitative, phenomenological approach was used to guide and analyze the interviews of twelve participants recruited through purposeful sampling. Patricia Benner's From Novice to Expert theory was used as both a theoretical definition of expert as well as a baseline for participants to self-identify with one of the levels of skill acquisition (novice, advanced beginner, competent, proficient or expert). Three themes emerged from data analysis including: 1) characteristics of expert nurses, 2) significance and impact of loss and 3) difficulty with the word "expert". The study results showed that expert is a fluid concept that is both difficult to define and maintain throughout a nurse's career. Factors such as education, technology, culture, environment and most notably autonomy, impact a nurse's ability to achieve expert status as well as the ability to remain an expert of the same capacity throughout their careers. In addition, environmental and practice related changes resulted in feelings of loss that also significantly impacted the nurse's perception of expert nursing. Ultimately, it was identified that Benner's definition of expert is not complete and would require additional research with a focus on relational and psychosocial elements of nursing specifically in the area of labour and delivery setting in order to achieve a more comprehensive definition.


Given two strings: pattern P of length m and text T of length n. The string-matching problem is to find all occurrences of the pattern P in the text T. We present a simple string-matching algorithm which works in average o(n) time with constant additional space for one-dimensional texts and two-dimensional arrays. This is the first attempt to the small-space string-matching problem in which sublinear time algorithms are delivered. More precisely we show that all occurrences of one- or two-dimensional patterns can be found in O(n/r) average time with constant memory, where r is the repetition size (size of the longest repeated subword) of P.


Why do we speak? Because we want to influence each other's behavior. The relevance of a speech act can measure its usefulness. In this paper I argue that (i) the relevance of a speech act depends on the 'language game' one is involved in; (ii) notions of relevance can be defined using decision, information and game theory, and can be used for linguistic applications; and (iii) the strategic considerations of participants in a conversation deserve our attention, especially when we consider mixed-motive games of imperfect information, for instance, to establish the common ground.


BACKGROUND
The meaning of the term "medico competente" - usually adopted in Italy to indicate the occupational physician - is little known.

OBJECTIVES
To describe the origins of the word "medico competente" in Italy.

METHODS
We conducted a comprehensive analysis of the Italian legislation from the end of the nineteenth century to the present day.

RESULTS
In the United Kingdom, occupational physicians were originally named as "certifying surgeon" (1833) and "appointed surgeon" (1860). In Italy, the term "medico delegato" was introduced to indicate the physician who visited child laborers (1886), while the word "medico competente" was first used in some propaganda leaflets of the Clinica del Lavoro of Milan in 1910. This term was officially used in Italian legislation in 1927 and was preferred to "medico di fabbrica" (factory physician) in the post-World War II period. Since 1982, the term "medico competente" has started to be considered as a synonym of occupational physician in Italian laws.

CONCLUSIONS
The name "medico competente" appears to derive from a legislative imposition rather than from a voluntary choice developed in a medical and scientific context. Nowadays, Italian occupational physicians should be stimulated to find scientific, ethical, and professional meanings in this term, so helping to enhance their figure in modern society.


Tobacco smoking is the leading avoidable cause of death and disability in the world. The UK is unique in that it offers a dedicated smoking cessation service providing behavioural support to all smokers, freely available through the National Health Service and with pharmacotherapy available at prescription cost. The service has been proven effective and cost-effective, yet only a small minority of smokers are currently using these services. The research in this thesis examines smokers' use of support and how more smokers might be identified and encouraged to use it.

The first study investigated whether proactive identification of smokers in a primary care setting and referral into such services is a potential means by which awareness and use of services may be increased. As such a study is reliant on the identification of smokers from primary care records and the accuracy of this data, a precursor to this study investigated the completeness and accuracy of smoking status recording in primary care medical records. General practices in this study had a smoking status recorded for between 42.4 and 100% of patients, and comparison of medical records with responses to self-completion questionnaires revealed that this recording is likely to be inaccurate in approximately 20% of cases. Even so, approximately 40% of smokers who responded to the questionnaire were interested in speaking to a smoking cessation advisor when asked, indicating that there is potential to intervene with smokers identified in this way in primary care and that there is a need which is currently not being met.

In the trial, all smokers in 12 intervention practices were proactively identified and offered referral into evidence based support, and compared to 12 'usual care' control practices, a significantly greater proportion of these smokers reported using local smoking cessation services (16.6% and 8.9% respectively). Validated 7-day point prevalence from smoking at 6 months was higher in the intervention than the control groups, although this difference was not statistically significant (3.5% and 2.5% respectively). Post-hoc analysis in the sub-group of smokers who had initially reported that they wanted to speak to a smoking cessation advisor did, however, reveal a significant difference between intervention and control groups (4.0% and 2.2% respectively). A proactive approach to enrolling smokers in smoking cessation services is, therefore, effective if you can identify smokers who want support for their quit attempt.

Use of an NHS support service traditionally involves some degree of pre-planning. Anecdotal evidence from the proactive trial indicated that many smokers did not pre-plan their quit attempts and as recent evidence from elsewhere has indicated that a large proportion of smokers make an attempt to quit smoking without any pre-planning, this may in part explain the relatively low proportion of smokers accessin0g services. The next study therefore was a questionnaire survey designed to investigate the occurrence, determinants and use of support in planned and unplanned quit attempts. The study findings revealed that over one third of quit attempts were made without pre-planning, and over half of these unplanned attempts were made without the use of any support and unplanned quit attempts appeared to be more likely to be successful, in line with previous findings. However, the use of evidence-based support is known to increase the likelihood of a quit attempt being successful and thus for each successful unplanned and unsupported quitter there are likely to be many more who are unsuccessful.

There has been no detailed exploration of how unplanned quitters engage in quit attempts, why they may or may not choose to use support and their attitudes to the support currently available. Gaining a greater insight into these factors may result in the identification of better ways to support those who make unplanned quit attempts. The final study therefore involved qualitative research with a group of unplanned quit attempters and revealed that smokers' reports of 'unplanned' quit attempts may indeed involve elements of planning and delay, and often this delay is in order to gain access to cessation support. The majority of smokers and ex-smokers interviewed were receptive to the idea of support being immediately available whether or not their last quit attempt had involved support. Engaging smokers in using support at an appropriate time, without the need to delay their quit attempt in order to achieve this, may be a potential means of increasing smokers' uptake of effective cessation support and subsequently improving quit rates. It is therefore important to investigate ways in which smoking cessation support can be made available to potential quitters within a much shorter timescale.


The current routine diagnostic procedures for foot and mouth disease (FMD) virus antigen detection combine the use of an indirect sandwich enzyme-linked immunosorbent assay (ELISA) with virus isolation and amplification on cell culture. Several field samples recently received by the World Reference Laboratory for Foot and Mouth Disease which were initially diagnosed as containing a single virus type have subsequently been found to contain an additional virus type. Examples are given of the results of ELISAs performed on certain Saudia Arabian samples; these examples illustrate the problem which such multiple-infected samples present for laboratory diagnosis.


1. Thyroid-accelerated metamorphosis in the larval frog is accompanied by changes in the hemopoietic centers and in the blood cell distribution in the various regions of the body. These changes are interpreted as results of the fundamental change in basal metabolic rate induced by the thyroid treatment. 2. There is initiation of the shift of hemopoietic locus from the kidney, the larval hemopoietic organ, to the spleen, the adult hemopoietic organ. The spleen, being chiefly an erythrocyte producer, becomes of greater importance with the transition from the lower metabolic rate to the higher, since greater erythropoiesis becomes necessary to supply the physical basis for the maintenance of the higher metabolic rate. 3. It is suggested that the appearance of red bone marrow in the later history of the frog is correlated with a still higher metabolic rate. Phylogenetically, in the vertebrate series, red bone marrow is also associated with higher metabolic rate. 4. The new metabolic rate initiated in tadpoles by thyroid administration sets up a demand for (a) erythrocytes, (b) granulocytes and lymphoid phagocytes for distribution to regions of regressive change, (c) lymphocytes, (1) as progenitors of erythrocytes, granulocytes and phagocytes, (2) for promoting growth of cells in regions of progressive change. 5. Upon the hemopoietic reserve, which in the last analysis is the lymphocyte (and its mesenchymal precursor), depends the extent to which metamorphosis will proceed. Inability on the part of the hemopoietic centers, chiefly the spleen, to keep pace with the demand for blood cells during metamorphosis results in metamorphic stasis, a condition of anemia which is usually followed by death. 6. The growth-promoting function of leucocytes, as demonstrated by Carrel, is probably to be ascribed to the lymphocyte component of leucocytes. 7. The granulocytes have probably also a glandular function, and may exert a lytic effect upon adjacent tissues in regions of regressive change.


In 1755 Lisbon was hit by an earthquake that almost completely leveled the city. The news of the catastrophe spread rapidly and the earthquake was soon discussed throughout Europe. Today the Lisbon earthquake is first and foremost known through the works of Voltaire and his discussions on the theodicy. However, the dominating European understanding was that the quake was caused by the wrath of God. The catastrophe was described in terms of exemplarity, and was interpreted as a god-given token. By a close reading of one the Danish poems about the quake, Christian Henric Bierings poetiske Tanker Over Lissabons A˜deleggelse ved det uhorlige Jordskiaelv paa Alle helgens Dag 1755, the article examines how the earthquake was framed as an example. By the use of examples, the poem argues for an understanding of the catastrophe as an omen predicting an imminent doomsday. By reading Biering's poem, the article explores the relationship between the early modern way of thought by the usage of examples and the readings and interpretations of omens.


Abstract.  The mechanisms involved in introduction, maintenance and perpetuation of epizootic haemorrhagic disease virus (EHDV) in South Africa are not fully understood. This paper reports on the susceptibility of South African livestock associated Culicoides (Diptera: Ceratopogonidae) species to oral infection with eight EHDV serotypes. Virus was recovered from eight of 17 field‐collected Culicoides species 10 days after oral feeding on blood/virus mixtures. Six EHDV serotypes were recovered from C. (Avaritia) imicola Kieffer, and seven serotypes were recovered from C. (A.) bolitinos Meiswinkel. Virus recovery rates in C. imicola ranged from 0.4% for EHDV 2 to 14.4% for EHDV 7, and in C. bolitinos from 0.6% for EHDV 6 to 12.3% for EHDV 2. There was a significant difference in virus recovery rates between serotypes in both species. Other Culicoides species that yielded EHDV after 10 days extrinsic incubation included C. (Meijerehelea) leucostictus Kieffer, C. (Culicoides) magnus Colaço, C. (Beltranmyia) nivosus de Meillon, C. (A.) gulbenkiani Caeiro, C. (Hoffmania) zuluensis de Meillon and C. onderstepoortensis Fiedler. Culicoides midges shown in this study to be susceptible to oral infection with EHDV are widely distributed in South Africa but differ considerably in their abundance, host preference and breeding sites.


Production of high titre, high avidity, polyclonal antisera to insulin was attempted in a number of animal species but was only successful in guinea-pigs. In particular, the use of Strain 2 guinea-pigs resulted in a 100% success rate (Chapter 3). Ten murine monoclonal antibodies (McAbs) were produced using porcine insulin and human proinsulin as immunogens. Six reacted with insulin and proinsulin, one with C-peptide and proinsulin, and three with proinsulin only (Chapter 4). The detection of McAbs specific for proinsulin required the preparation of monoiodinated 125I-proinsulin. This involved the development of a reverse-phase high performance liquid chromatography (HPLC) technique to separate the various iodinated species of 125I-proinsulin (Chapter 5, Section 1.2). A two-site immunoradiometric assay (IRMA) for human insulin was developed using the guinea-pig anti-insulin in conjunction with an insulin McAb raised using porcine insulin as immunogen. Proinsulin cross-reacted in the assay to a degree dependent upon the form being measured and its concentration (Chapter 5, Section 2). Initial evaluation suggested that the avidity of the C-peptide McAb was too low to provide a proinsulin IRMA of the required sensitivity (Chapter 5, Section 4). Subsequent reassessment with the previously unavailable NIBSC proinsulin standard and a higher avidity insulin McAb suggested that a potentially useful assay could be developed (Chapter 5, Section 6.3). The highest avidity proinsulin-specific and insulin McAbs, raised using human proinsulin as immunogen, were used in a two-site IRMA to measure human proinsulin. The presence of insulin interfered with the initial assay developed (Chapter 5, Section 5) and the protocol was modified to abolish this effect (Chapter 5, Section 6). The assay measured intact, 65-66 split and des 64-65 proinsulin. Clinical validation of the assays developed was performed by measuring insulin and proinsulin concentrations in serum from normal adult subjects under a variety of conditions (Chapter 6, Section 1). The release of proinsulin relative to insulin was found to be delayed in response to an increase in blood glucose concentrations. Serum proinsulin and insulin concentrations were also measured in patients in various states of altered or patho-physiology. Measurement of fasting proinsulin compared to insulin concentrations provided improved discrimination in the diagnosis of insulinoma (Chapter 6, Section 2.3). The reported association between cirrhosis of the liver and glucose intolerance, hyperinsulinaemia and hyperproinsulinaemia was confirmed although the data suggested that only hyperinsulinaemia was truly secondary to the development of cirrhosis. The hyperinsulinaemia appeared to be due to reduced degradation rather than hypersecretion (Chapter 6, Section 2.5). Data is presented which supports the role of insulin resistance in the development of impaired glucose tolerance in pregnancy (Chapter 6, Section 2.2) and the high circulating concentration of insulin in a boy with Mendenhall's Syndrome (Chapter 6, Section 2.4). However, an abnormal pattern of insulin secretion in the basal state also appears to contribute to the hyperinsulinaemia in Mendenhall's Syndrome. The glucose intolerance has also been shown to be due to an abnormal pattern of insulin release in response to increased blood glucose concentrations in patients with non-insulin dependent diabetes mellitus (NIDDM) (Chapter 6, Section 2.1) and cirrhosis of the liver (Chapter 6, Section 2.5). From the clinical data presented in this thesis, it is hypothesised that two pools of insulin exist, only one of which contains intact proinsulin. It is hypothesised that the pattern of release of insulin from these pools varies in the basal and stimulated states, and that various pathophysiological conditions, including insulin and noninsulin dependent diabetes mellitus, exhibit altered patterns of secretion which are characteristic of the underlying disease mechanism.