We reviewed 160 diaphyseal and metaphyseal fractures of the femur and tibia in children treated between 1964 and 1980 at the Orthopaedic and Traumatological Clinic of the University of Rome. The initial documentation was complete in these cases and 96 presented for clinical and radiographic long-term follow-up. The analysis of this material showed that lengthening of the affected limb had occurred in 46% of cases. The amount of such lengthening, however, was only from 0.5 to 1.5 cm and never exceeded 2 cms. It was most frequent in children between the ages of 3 to 8 years with fractures of the tibia, particularly in the upper third of the bone.


I HAD the honour to exhibit before the Society about two years ago, the body of an infant who had died of a severe gangrenous eruption, which had followed vaccination. I believed that it was an example of "Vaccinia gangrenosa," i.e. a vaccinia eruption which had taken on a gangrenous form. I now purpose to bring before the Society the details of the case, and also to give some account of an allied and much more common malady to which for many years past I have applied the name " Varicella gangrenosa."


The electron-stimulated production of D2 from amorphous solid D2O deposited on Pt(111) is investigated as a function of film thickness. The D2 yield has two components that have distinct reaction kinetics. Using isotopically layered films of H2O and D2O demonstrates that the D2 is produced in reactions that occur at both the Pt/amorphous solid water (ASW) interface and the ASW/vacuum interface, but not in the bulk. The energy for the reactions, however, is absorbed in the bulk of the films and electronic excitations diffuse to the interfaces where they drive the reactions.


In the context of social media, the controversial marketing represents a new marketing strategy, but there is enough attention in the academic circles, and the understanding of the controversial marketing was blurred. According to the existing researches, we introduce the concept of controversial marketing and briefly describe that controversial topic is how to cause conversation.In order to apply controversial topics scientifically and promote the development of research in this field, we propose some research topics which are worthy to discuss in the future.


Abstract Objective: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use. Significance: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use. Methods and results: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2 nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box–Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5 ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation. Conclusion: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.


Autonomous vehicles are an emerging technology that will play a significant role in shaping transport systems in the decades to come. Consequently, implications are anticipated for societal issues ranging from transport safety to congestion, from energy consumption to the allocation of public and private lands. Driverless technology will undoubtedly influence other transport modes, too. With this in mind, the implications for pedestrians have hardly been researched. If the introduction of driverless cars could ultimately result in the disappearance of on-street parking spaces and in crossing streets without so much as glancing towards approaching cars, this could potentially mean that walking becomes much more attractive. At the same time, one could imagine the opposite outcome if society decides that the ability of being picked up and dropped off at any front door or location imaginable renders walking as a state-supported transport mode superfluous. The purpose of this paper is to discuss the impact of autonomous vehicles on pedestrian transport in all its aspects, including the range of possible outcomes, interdependencies, and opposing effects. With the state-of-the-art of pedestrian transport research as a starting point, how can the needs of pedestrians be taken into consideration when fully autonomous vehicles become ubiquitous in daily life?


Background : The aim of the present study was to investigate the relationships between mood states and competitive state anxiety and perceived performance in Asian male baseball players from universities in choking under pressure situations during a game. An additional aim was to identify the mediating effect of competitive state anxiety on such relationships. Methods : A questionnaire was administered to 209 male baseball players from universities who wanted to enter a professional league. The mean age of study subjects was 20.25 years. Structural equation modeling and bootstrapping analyses were used to test hypotheses and analyze the mediation effect. Results : First, among mood states, higher confusion and higher tension predicted higher competitive state anxiety. Second, mood states had no significant influence on perceived performance. Third, higher competitive state anxiety predicted lower perceived performance. Lastly, competitive state anxiety had a complete mediating effect on the relationship between mood states and perceived performance. Conclusions : To help athletes perform to the best of their ability, psychological interventions should be provided with a greater focus on reducing competitive state anxiety during a game. And we believe that an intervention program with a greater focus on competitive state anxiety can provide a more realistic and effective assistance scheme which will prevent a sudden decrement in performance


Importance of climate change and its impact on agriculture and environment has increased with a rise of greenhouse gases (GHGs) concentration in Earth's atmosphere, which had caused an increase of temperature in Earth. Greenhouse gas emissions such as methane() and nitrous oxide() in the field need to be assessed. GHGs fluxes using chamber systems in the fields(2004~2005) with pepper cultivation were monitored at the experimental plots of National Academy of Agricultural Science(NAAS), Rural Development Administration(RDA) located in Suwon city. emission during pepper growing period was reduced to 74.0~82.1% in sandy loam soil compared with those in clay loam soil. Evaluating emission at different levels of soil water conditions, emission at -50 kPa were lowered to 13.2% in clay loam soil and 40.2% in sandy loam soil compared with those at -30 kPa. emission was reduced to 45.7~61.6% in sandy loam soil compared with those in clay loam soil. Evaluating at different levels of soil water conditions, emission at -50 kPa was lowered to 69.6% in clay loam soil and 55.8% in sandy loam soil compared with those at -30 kPa. It implied that -50 kPa of soil water potential was effective for saving water and reducing GHG emissions. From the path analysis as to contribution factors for emission, it appeared that contribution rate was in the order of mineral N(51.2%), soil temperature (25.8%), and soil moisture content(23.0%) in clay loam soil and soil moisture content(39.3%), soil temperature (36.4%), and mineral N(24.3%) in sandy loam soil.


In this paper, we introduce a novel double gate SHOT which provides at least the drain current twice higher than that of the conventional SHOT structure. Improved characteristics are originated from the high velocity electron injection at the source edge due to the band offset energy. The analysis of the off-state current characteristics shows that provided 89% reduction in off-stat current. Based on this analysis, we proposed use of work function engineering as well as extra grounded gate to minimize the magnitude of GIDL current which is the main component of the off-state current.


Background Hepatocellular carcinoma (HCC) is one of the most prevalent cancers, and its incidence rate is increasing worldwide. At present, there is no ideal treatment for HCC. In recent years, molecular-targeted therapy has shown significant therapeutic benefits for patients. Ferroptosis is a modality of regulated cell death, and previous studies have found that inducing ferroptosis in liver cancer cells can inhibit the progression of liver cancer. The aim of this study is to investigate the regulatory mechanism of miR-21-5p in regulating ferroptosis in HCC cells. Methods CCK-8 was used to measure cell viability, EdU and colony formation were used to measure cell proliferation, and Transwell assays were used to measure cell migration and invasion. RT-qPCR was used to detect the level of miR-21-5p, Western blotting was used to detect the protein expression level, a dual-luciferase reporter gene assay was used to determine the targeting relationship between miR-21-5p and MELK, and coimmunoprecipitation was used to determine the interaction between MELK and AKT. Results Overexpression of miR-21-5p and MELK facilitated the viability, proliferation, colony formation, invasion, and migration of HCC cells. Downregulation of miR-21-5p suppressed the level of MELK and the progression of HCC. MELK regulated the AKT/mTOR signaling pathway, causing changes in the levels of GPX4, GSH, FTH1, xCT, heme oxygenase 1(HO-1), reactive oxygen species, and Fe2+ to regulate the ferroptosis of hepatoma cells. Erastin, an inducer of ferroptosis, attenuated the repressive influence of miR-21-5p on ferroptosis in HCC cells. Conclusion In summary, this study demonstrates that miR-21-5p inhibits the ferroptosis of HCC cells by regulating the AKT/mTOR signaling pathway through MELK.


A depressurization accident involving the rupture of the primary cooling pipe of the Gas Turbine High Temperature Reactor 300 cogeneration (GTHTR300C), which is a very-high-temperature reactor, is a design-based accident. When the primary pipe connected horizontally to the side of the reactor pressure vessel of GTHTR300C ruptures, molecular diffusion and local natural convection facilitate gas mixing, in addition to air ingress by counter flow. Furthermore, it is expected that a natural circulation flow around the furnace will suddenly occur. To improve the safety of GTHTR300C, an experiment was conducted using an experimental apparatus simulating the flow path configuration of GTHTR300C to investigate the mixing process of a two-component gas of helium and air. The experimental apparatus consisted of a coaxial double cylinder and a coaxial horizontal double pipe. Ball valves were connected to a horizontal inner pipe and outer pipe, and the valves were opened to simulate damage to the main pipe. As a result, it was confirmed that a stable air and helium density stratification formed in the experimental apparatus, and then a natural circulation flow was generated around the inside of the reactor.


The medical doctor's status within the South African juridical praxis of abortus provocatus is examined. A comparison is drawn between the situation in South Africa and that in the rest of the world. A cursory appraisal of the ontological status of the unborn in the Judeo-Christian tradition delineates ethical norms that do not perforce correspond with the abovementioned juridical praxis. The author attempts to answer the question whether the South African law concerning abortus provocatus is a good law.


Background: Bioelectrical impedance vector analysis (BIVA) is a non-invasive assessment of body composition and cellular health, which may improve the assessment of nutritional status in sick children. We explored the reliability, clinical utility, and acceptability of BIVA, as an indicator of nutritional status for children under five years with and without pneumonia, in Malawi. Methods: We conducted a parallel convergent mixed-methods exploratory study in Mchinji District Hospital, Malawi, in 2017. We planned to recruit a convenience sample of children aged 0-59 months with clinical pneumonia, and without an acute illness. Children had duplicate anthropometric and BIVA measurements taken. BIVA measurements of phase angle (PA) were taken of the whole body, and trunk and arm segments. Reliability was assessed by comparing the variability in the two measures, and clinical utility by estimating the association between anthropometry and PA using linear regression. Focus group discussions with healthcare workers who had not previously used BIVA instrumentation were conducted to explore acceptability. Results: A total of 52 children (24 with pneumonia and 28 healthy) were analysed. The reliability of sequential PA measurements was lower than anthropometric measurements, but trunk and arm segments performed better. The largest associations with PA were a negative relationship with weight-for-age z-score (WAZ) and PA in children with pneumonia in the trunk segment, and a positive association with WAZ in the full body measurement in healthy children. Healthcare workers in focus group discussions expressed trust in BIVA technology and that it would enable more accurate diagnosis of malnutrition; however, they raised concerns about the sustainability and necessary resources to implement BIVA.  Conclusions: While healthcare workers were positive towards BIVA as a novel technology, implementation challenges should be expected. The differential direction of association between anthropometry and PA for children with pneumonia warrants further investigation.


This thesis will present research that studies the role of disorder, geometric frustration and the long-range dipolar interaction on the collective behaviour of several insulating, rare earth magnets. Experiments were performed at low temperatures to measure the specific heat and magnetic susceptibility of several materials. Susceptibility was measured with a SQUID magnetometer that has been designed and constructed primarily for the study of slow dynamics in glassy systems. Specifically, this thesis will discuss three distinct topics. The first is the series of materials LiHoxY1−xF4, which are manifestations of the dilute, dipolar coupled Ising model. The low-x portion of the phase diagram has become a rather contentious issue in recent years with both theoretical and experimental groups disagreeing on the existence of a spin glass freezing transition and one experimental group arguing for the existence of an exotic "antiglass" or spin liquid state resulting from quantum entanglement at x = 0.045. We present specific heat and dynamical susceptibility measurements on four stoichiometries in this series: x = 0.018, 0.045, 0.080 and 0.012. No evidence of an unusual antiglass state is observed. Instead, our results show evidence, at all dilution levels studied, of a spin glass freezing transition. Interpretation of experimental data is found to be complicated by the anomalously slow dynamics in these materials. The relaxation time scales are found to increase as the concentration of Ho ions is reduced, an effect which can be attributed to single-ion physics and the importance of the nuclear hyperfine coupling in this system. A second set of materials studied here is a series of several Gd garnet materials, the most famous of which is Gd3Ga5O12 (GGG), a material previously argued to be a disorderfree spin glass. Our specific heat experiments reproduce previous experiments on GGG and show that the homologous Gd garnets Gd3Te2Li3O12 and Ga3Al5O12 do not share the same glassy physics but exhibit sharp ordering features. By experimenting with the introduction of random site dilution, it is concluded that a 1-2% off-stoichiometry inherent in GGG is likely a special kind of disorder that is particularly effective in inducing random frustration and the formation of a spin glass. Finally, specific heat measurements on the pyrochlore antiferromagnet Gd2Sn2O7 (GSO) are presented. While GSO has generally been found to be a well behaved and well understood model magnet, with long range order developing at around 1 K, like many other geometrically frustrated magnets, it has been discovered to possess persistent spin dynamics down to very low temperatures as measured by μSR and Mössbauer spectroscopy. Measurement of the low temperature limit of the specific heat when compared with linear spin-wave theory, however, presents a consistent picture of gapped magnon excitations that freeze out at low temperatures and make the existence of the proposed dynamic ground state unlikely.


A mathematical model of the evaporation of a polydisperse ensemble of drops, with allowance for a nonlinear 'diffusion' term in the kinetic equation for the population density distribution function, is developed. The model describes the interaction of a gas phase with vaporizing drops: it has great potential for application in condensed matter physics, thermophysics and engineering devices (e.g. spray drying, cooling, power engineering). The kinetics of heat transfer between phases is theoretically studied. An analytical solution to the integro-differential equations of the process of droplet evaporation is found in a parametric form. Analytical solutions in the presence and absence of the 'diffusion' term are compared. It is shown that the fluctuations in particle evaporation rates ('diffusion' term in the Fokker–Planck equation) play a decisive role in the evolutionary behaviour of a polydisperse ensemble of vaporizing liquid drops. This article is part of the theme issue 'Transport phenomena in complex systems (part 1)'.


The effect of the temperature and duration of thermal treatments of nopalitos on the carotenoid content, phenolic compound content and antioxidant activity was evaluated. The nopalitos were roasted or fried at three temperatures and six time intervals. HPLC and spectroscopic methods t evaluate the modification on the carotenoids, phenolic compounds content and antioxidant activity were used. No correlation between antioxidant activity and carotenoids content in nopalitos, either fried or roasted, was found. The highest antioxidant activity was found in roasted nopalitos (125 oC; 30 min), however at these conditions, the lowest concentration of carotenoid was obtained. The highest content of phenolic compounds was obtained from roasted nopalitos (75 oC; 20 min). Both thermal treatments, fried and roasted modified the nut aceutical characteristics of nopalitos. Palabras clave: Opuntia ficus, nopalito, antioxidant activity, thermal treatment.


Abstract This paper discusses Hacking Hearts, a transdisciplinary educational collaboration between the art school Central Saint Martins (U.K.) and a science and engineering university, the Tokyo Institute of Technology (Japan). The concept of performativity—which was brought into the construction of the workshop setting—is used to explain the mechanisms of interaction across disciplinary boundaries commonly accepted in these institutions and academic areas. The collaboration transformed performative elements into a resource by creating an educational environment that enabled communication through encounters "on stage" between research scientists and art/design students. The discussion is situated within a growing literature on art/science education and offers lessons for establishing collaborative workshops between diverse participants.


The epidemiologic studies with the least selection bias do not support the hypothesis that HPV types 16 and/or 18 are strongly associated with cervical cancer. In this preliminary report, we describe our findings regarding type 16, 18, and 33 detection rates in 323 normal and 71 dysplastic or neoplastic cervical scrapes using fast multiplex PCR. This modified PCR technique has been shown to be the most sensitive, specific, and reproducible DNA detection method for large epidemiologic studies. The results indicate a high relative risk of increasingly severe cervical abnormality associated with the presence of high-risk HPV DNA. The analysis of the prevalence and age data according to CIN status by non-parametric statistic tests highlights the importance of other factors inversely correlated with age in the cervical transformation process.


Four self-assessed health ratings were examined for their reliability, concurrent validity, and predictive utility in women aged 70 and older. The Perceived Well-Being (PWB) Scale and self-rated health were two subjective measures; the two objective measures were reported number of prescription medications and a medical symptom index from the Canada Fitness Survey. Four-week test-retest reliabilities ranged from .51 to .86. Significant concurrent validity was obtained among all four instruments, with the strongest association between PWB and SRH (r = .569, p < .001). The best predictor of late-life exercise was PWB, which explained 8% of the variance in involvement.


Cocrystals have gained much interest in recent years owing to their potential to improve the physicochemical properties of the parent compounds. It was once thought that cocrystals could be a means to prevent polymorphism but many recent examples of cocrystal polymorphism have been discovered and reported. Similar to single component crystals, polymorphs of cocrystals can display significantly different properties. In this contribution, we present a survey of polymorphic cocrystals. The different types of polymorphs, namely synthon, conformational, packing, and tautomeric, are identified and discussed with representative examples. In addition, polymorphs of cocrystals that showed distinct physicochemical properties are highlighted.


'places consecrated to God [should] be venerated by all, and by no means profaned or in any way violated by a jarring or unsuitable activity, whether in working, jesting or playing …; [there should be] no laughter, shouting, immoderate mirth, indecent and indiscreet dances, indecent mockeries and harmful plays proper to the market-place or the stage': letter of Bishop Edmund Lacy of Exeter, 1451 Old churchyards enshrine vast amounts of personal and social history, although most of it, sadly, is not recoverable. Furthermore, they often display a romantic and touching beauty. When exploring villages and towns in all parts of Britain, many of us have been moved by the sight of a raised platform of hummocky turf surrounding an ancient Christian church, walled and gated, crossed by narrow paths, shaded by mature trees, dotted with leaning headstones and lichened table-tombs, perhaps with the weathered stump of a medieval preaching cross. Above all we are impressed by the thought that most of the local population, over many centuries, lies here, 'each in his narrow cell for ever laid'. For example, a rural churchyard of half an acre at Widford in Hertfordshire is estimated to hold more than 5,000 burials, laid to rest over a period of at least 900 years. Such places have witnessed many solemn rituals: consecration by a bishop, occasional claims of sanctuary, sad clusters of mourners around open graves, the commemorative prayers and bell-ringing of All Saints' and All Souls' days, parochial processions on Palm Sunday or Corpus Christi, and at all periods the lonely vigils of the bereaved. Repeatedly opened and re-filled by generations of gravediggers, churchyards are potent reminders of human mortality which the living have mostly treated with respect, deep reflection and some superstition.


In surgical procedures intra- and postoperative cardiopulmonary complications rank first in the elderly patient. Cardiovascular risk factors in the preoperative judgement include chronic cor pulmonale, coronary heart disease and cardiac rhythm disturbances. Moreover pulmonary-respiratory risks and arterial hypertension play a very important role. In order to lower the intra- and postoperative risks, it is necessary to establish a thorough preoperative diagnosis and to establish a differential therapeutic work-up considering the underlying heart disease. Here balanced electrolytes seem to be particularly important. Only under these circumstances it will be possible to perform major surgical procedures in the elderly patient with an acceptable risk.


A highly specific and sensitive enzyme immunoassay system for the quantitative determination of haprin in the air at a concentration of not less than 0.0001 mg of haprin per m3 of air has been developed. The assay system has been approved at the Svetloiarsk plant for the production of vitamin protein concentrate and can be used for the control and evaluation of haprin pollution of the environment at areas adjoining microbiological plants.


In order to optimize the costs and time of design of the new products while improving their quality, concurrent engineering is based on the digital model of these products, the numerical model. However, in order to be able to avoid definitively physical model, old support of the design, without loss of information, new tools must be available. Especially, a tool making it possible to check simply and quickly the maintainability of complex mechanical sets using the numerical model is necessary. Since one decade, our team works on the creation of tool for the generation and the analysis of trajectories of virtual mannequins. The simulation of human tasks can be carried out either by robot-like simulation or by simulation by motion capture. This paper presents some results on the both two methods. The first method is based on a multi-agent system and on a digital mock-up technology, to assess an efficient path planner for a manikin or a robot for access and visibility task taking into account ergonomic constraints or joint and mechanical limits. In order to solve this problem, the human operator is integrated in the process optimization to contribute to a global perception of the environment. This operator cooperates, in real-time, with several automatic local elementary agents. In the case of the second approach, we worked with the CEA and EADS/CCR to solve the constraints related to the evolution of human virtual in its environment on the basis of data resulting from motion capture system. An approach using of the virtual guides was developed to allow to the user the realization of precise trajectory in absence of force feedback. The result of this work validates solutions through the digital mock-up; it can be applied to simulate maintenability and mountability tasks.


We consider a Langevin equation of active Brownian motion which contains a multiplicative as well as an additive noise term. We study the dependences of the effective diffusion coefficient Deff on both the additive and multiplicative noises. It is found that for fixed small additive noise intensity Deff varies non-monotonously with multiplicative noise intensity, with a minimum at a moderate value of multiplicative noise, and Deff increases monotonously, however, with the multiplicative noise intensity for relatively strong additive noise; for fixed multiplicative noise intensity Deff decreases with growing additive noise intensity until it approaches a constant. An explanation is also given of the different behavior of Deff as additive and multiplicative noises approach infinity, respectively.


The ability of the human 5-HT(1A) receptor to activate different recombinant G(alpha) proteins was investigated in CHO-K1 cells by monitoring 5-HT ligand-mediated Ca(2+) responses upon co-expression with either G(alphaq), G(alpha15) or chimeric G(alphaq/i3) proteins. Each G(alpha) protein yielded a typical 5-HT-dependent Ca(2+) response with different kinetic parameters both for the onset-time of maximal Ca(2+) response (21 to 30 s) and time-dependent attenuation (43 to 73% of residual activity at 1 min upon peak Ca(2+) response). Pertussis toxin-treatment fully abolished the Ca(2+) responses mediated by both the endogenous G(i/o) and the chimeric-PTX-sensitive G(alphaq/i3) proteins. In contrast, Ca(2+) responses driven by recombinant G(alphaq) and G(alpha15) proteins were decreased by PTX, respectively by 52% and 35%, corresponding to the level of endogenous G protein activation. The pharmacology of the 5-HT ligand-mediated Ca(2+) responses was highly affected by both the presence and nature of the co-expressed G(alpha) protein. This influence was more pronounced for the partial agonists L 694247, 8-OH-DPAT, flesinoxan and buspirone in contrast to ipsapirone. The G(alpha) protein rank order for apparent increase of ligands' intrinsic activity was: G(alphaq) <G(alphaq/i3) <G(alpha15) protein. Each of the 5-HT-mediated Ca(2+) responses could be antagonised by WAY 100635, buspirone and methiothepin regardless of the absence or presence of a G(alphaq), G(alphaq/i3) or G(alpha15) protein. In conclusion, these data reinforce that depending on the presence and nature of the G(alpha) protein environment, 5-HT(1A) ligands may display a large spectrum of activities.


BACKGROUND
Depression is a common mental health problem in the geriatric population associated with significant morbidity (including decreased physical, cognitive and social functioning) and mortality. Although patients differ in their presentations, certain social and demographic characteristics are common to the elderly population with depression. It is hoped that identifying these patients based on their sociodemographic characteristics will help reduce the difficulties in diagnosis.

OBJECTIVE
The objective of this study is to determine the risk factors for depressive illness among elderly patients attending the GOPD of AKTH.

METHODS
This cross-sectional questionnaire-based study involved 392 elderly patients systematically selected from Family Medicine Clinic attendees in Kano, Nigeria. Data collected included sociodemographic and clinical characteristics. Geriatric Depression Scale was used to screen for depression. Chi-square test and logistic regression analysis were used to determine the association between categorical variables and predictors of depression among participants, respectively.

RESULTS
The prevalence of depression prevalence was 22.4%. Most participants were females aged 60-69 years (62.5%), Hausas (77.6%) and living with their spouses and children (77.3%). Gender, marital status, marital setting, socio-economic class, osteoarthritis and body-mass index were associated with depression. The predictors of depression were female gender (p=0.014, OR=1.401, CI=1.757- 2.591), widows/widowers (p=0.030, OR=4.533, CI= 1.186-17.317) and obesity (p=0.001, OR=5.644, CI=2.759-11.544).

CONCLUSION
The high prevalence of depression among this population highlights the need for screening. Females, widows/ widowers and obese geriatric patients are more likely to be depressed and should be targeted for screening in our busy outpatient setting.


During this study, mechanical and physical properties of the obtained sample are examined as a conclusion of waste marble dust addition as a filler material into the glass fibre included concrete. For this purpose, during the production of the concrete sample which was 300 and 350 dosages prepared, 5, 10, 15 and 20 kg/m3 ratio clipped glass fibre added to the mixture besides filler material and %25, 50, 75 and 100 volume ratio waste marble dust which can be used in place of filler material. Porosity, sorptivity, ultrasonic pulse velocity, splitting tensile strength and compressive strength experiments are performed on the obtained samples. As a result of this study, compressive strength, splitting tensile strength and ultrasonic pulse velocity of obtained samples which are obtained by the addition of waste marble dust to glass fibre concrete increased but porosity and sorptivity values decreased.


The authors report the clinical case of a 12-year-old boy with an extensive superficial venous network in almost every area of the body, present since birth and worsening in recent months, with the occurence of superficial venous thrombosis. No other changes on physical examination were noted, no symptoms and no analytical or imaging findings were found. Histological examination of the lesions revealed ectatic superficial veins without any proliferation of endothelial cells and the amount of elastin in the walls of these veins was decreased. The patient was diagnosed as a Bockenheimer's syndrome. The main features of this rare syndrome are described and discussed.


Abstract Stoimenow and Kidwell asked the following question: let K be a non-trivial knot, and let W(K) be a Whitehead double of K. Let F(a, z) be the Kauffman polynomial and P(v, z) the skein polynomial. Is then always max degzPW(K) − 1 = 2 max degzFK? Here this question is rephrased in more general terms as a conjectured relation between the maximum z-degrees of the Kauffman polynomial of an annular surface A on the one hand, and the Rudolph polynomial on the other hand, the latter being defined as a certain Möbius transform of the skein polynomial of the boundary link ∂ A. That relation is shown to hold for algebraic alternating links, thus simultaneously solving the conjecture by Kidwell and Stoimenow and a related conjecture by Tripp for this class of links. Also, in spite of the heavyweight definition of the Rudolph polynomial {K} of a link K, the remarkably simple formula {◯}{L#M} = {L}{M} for link composition is established. This last result can be used to reduce the conjecture in question to the case of prime links.


Abstract The international investment arbitration system between investors and host countries originated from the international commercial arbitration system. International investment disputes are usually disputes caused by the host country's policies to protect public interests and the dissatisfaction of private investors caused by regulations. There are few methods for intelligently recommending judgment documents based on factual texts in international investment arbitration cases. Because of this, this paper proposes a recommendation algorithm for international investment arbitration adjudication documents based on multimodal feature fusion. This paper teaches the structural information of paragraph tags and the relationship between paragraph contexts and incomplete judgment documents. The algorithm achieves a good structuring effect of international investment arbitration documents.


Compensation of Forced Labourers. Forced Labour for the German economy during the World War II and its compensation: starting positions – negotiations – results. This study deals with the process of compensation of Forced Labourers. It describes first the unwillingness of Germany to deal with the problem of Forced Labour and then the circumstances that set off a process that finally led to compensation. The core of the study is a very detailed description of diplomatic negotiations in the years 1999–2000, in the course of which representatives of the Federal Republic of Germany, the German industry, the USA, the states of Central and Eastern Europe and of the victims finally agreed to set up a foundation, funded one half each by the German state and by the German industry. Keywords: Forced Labour, Federal Republic of Germany, Czech-German Fund for the


A family of three nitric oxide synthase 1(NOS) isoforms produces nitric oxide (NO*) and L-citrulline via a stepwise oxidation of the guanidinium nitrogen of L-arginine. Akin to cytochrome P450 (P450)-catalyzed monoxygenations, the NOS reactions are dependent on both molecular oxygen and NADPH. Although all three NOS isoforms (two constitutively-expressed isoforms; neuronal (nNOS) and endothelial (eNOS), and one inducible isoform; (iNOS)) produce identical products, the function of the NO* varies widely in terms of physiological functions due to the varied localization of the isoforms within different cell populations of the body. The NOS isoforms are homo-dimeric, bi-domain enzymes. Each monomer consisting of a flavin-containing reductase domain linked to a heme-containing oxygenase domain by a calmodulin (CaM)-binding sequence located between the two domains. The reductase domains of the NOS isoforms not only possess close sequence and structural homology to NADPH-cytochrome P450 oxidoreductase (CPOR), but also, owing to the flavins, resemble CPOR in function in that the reductase permits the passage of electrons from a NADPH-derived hydride, one at a time, to the NOS oxygenase domain. Although possessing very little structural resemblance to P450, the oxygenase domain of NOS is referred to as being "P450-like" due to the presence of iron protoporphyrin IX (heme), linked axially by a cysteine to the NOS protein, which carries out "P450-like" mono-oxygenation reactions. Considering the importance of NO* in regulating many physiological functions, the NOS isoforms are important drug targets. Modulators (both inhibitors as well as possible activators) of enzymatic function are needed to either decrease or increase NO* production, respectively, in various disease states. In addition to the widely known beneficial processes where NO* plays a role (i.e. neurotransmission, blood pressure regulation, immunomodulation), under certain conditions production of NO* (as well as other NOS-derived oxidants) can be detrimental by altering enzyme activity; for example P450-mediated drug metabolism. Furthermore, because of the close structural and functional similarities between NOS reductase and CPOR, many of the same redox-cycling and reductive reactions that occur with CPOR can also occur with NOS. The final focus of this review article is the less-well-recognized reactions mediated by NOS, which have recently begun to receive the attention they deserve. We hope to highlight reasons for concern regarding both altered drug metabolism as well as extra-hepatic, and target-organ toxicities in response to both altered NO* production as well as the detrimental interaction of NOS with certain xenobiotics.


Older people can often fall on the wrong side of the 'digital divide' in terms of accessing and enjoying new digital technology. One approach to this issue is to provide training programmes and customisation techniques for using existing technology. However, another is to re-invent technology with and for older people themselves. In this paper, I propose four recommendations for re-invention, and illustrate these with examples in the domain of digital photography.


The subtropical part of the eastern Australian seaboard experiences intense cyclonic activity. The severe damage caused by the intense storms in the region, known as east coast lows (ECLs), has motivated a number of recent studies. Cyclones in this region appear to be driven by a combination of different (barotropic and baroclinic) formation mechanisms, consistent with the view emerging in the last decades that cyclones span a continuous spectrum of dynamical structures, with the barotropically driven tropical cyclone and the baroclinically driven extra-tropical cyclone being only the extremes of such spectrum. In this work we revisit the climatology of cyclone occurrence in the subtropical east coast of Australia as seen in a global reanalysis, systematically applying classification criteria based on the cyclone vertical structure and thermal core. Moreover, we investigate the underlying processes driving the cyclone rapid intensification by means of an atmospheric limited area energetics analysis. We show that ECLs have different spatial patterns according to the cyclone thermal structure, with the fraction of hybrid cyclones being larger towards the tropics and closer to the coast. Moreover, we find that explosively deepening cyclones in this region are driven by a different combination of processes with respect to the global case, with barotropic processes in the surrounding environment having a more dominant role in the energetics of cyclone rapid intensification. The findings of this work contribute to understanding the physical processes underlying the formation and intensification of Australian east coast lows and the associated coastal damage and risk. 14


Greta Manfrin joined Vets Now through its Cutting Edge programme. Here, she describes a recent working week as the principal vet at an out-of-hours pet emergency clinic in Gillingham, Kent.


The worldwide incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades. The reasons behind this phenomenon are not yet fully understood. Early life infections, prenatal and perinatal factors, and diet composition have been associated with the triggering of autoimmunity and the risk of presentation of T1DM. However, the rapid increase in new cases of the disease raises the hypothesis that lifestyle factors, which have traditionally been associated with type 2 diabetes, such as obesity and unhealthy eating patterns could also play a role in the genesis of autoimmune diabetes. This article aims to highlight the changing epidemiology of T1DM and the importance of properly recognizing the environmental factors behind it, as well as the connections with the pathogenesis of the disorder and the need to prevent or delay T1DM and its long-term complications.


In this article, we discuss a study to identify an effective agricultural knowledge transfer channel for smallholder farmers in Ethiopia, using a randomised training experiment together with focus group discussions, key informant interviews and a survey. We also examine the factors that determine learning among smallholder farmers. Our results revealed that involving extension agents and model farmers leads to above-average knowledge transfer. However, learning from extension agents is significantly more effective than learning from model farmers. Additionally, we found that trust, effort, and locus of control are important determinants of learning. On the other hand, we found no evidence that farmers exert more effort when they are trained by extension agents, hence this rules out effort as a mechanism for higher learning from the extension agents. Based on these results, we conclude that, on average, the extension agent system is more effective at conveying agricultural knowledge than model farmers are and that policy-makers can use the two channels as complements rather than substitutes.


In this study, we compared the level of myogenic tone and its negative-feedback control through specific K+ channels in two types of human veins (saphenous [SV] and cephalic [CV] veins), which experience different ranges of pressure in vivo. We also investigated whether an experimental model of increased venous pressure in rats exposed to head-up tilt for 2 weeks produced changes similar to those observed in the human veins. Cylindrical vein segments were cannulated, their diameters were measured, and the intraluminal pressure was set at different levels (2 to 30 mm Hg) in vitro. Acetylcholine test showed that during the regular harvesting process 76% of the human SVs exposed for coronary bypass grafts had no functional endothelium. We found significant myogenic tone in the human SV, where the in vivo pressure is high, but it was not present in the human CV, where the in vivo pressure is low. The nonspecific K+ channel antagonist, tetraethylammonium (TEA), decreased the diameter of the human SV but not the CV. Iberiotoxin and 4-aminopyridine, blockers of the Ca(2+)-sensitive (KCa) and voltage-gated K+ (KV) channels, also decreased the diameter of the human SV by 10.2 +/- 4.8% and 19.5 +/- 4.7%, respectively. In the rat SV, significant myogenic tone was found, but TEA had no effect, even after 2 weeks of in vivo pressure increase in the hindlimb by head-up tilt. We conclude that (1) an increased venous myogenic tone correlates with higher chronic intraluminal pressure loads, (2) KCa and KV channels counterregulate the myogenic tone in human, but not in rat, saphenous vein, (3) the counterregulatory effect is more effective at high than at low intraluminal in vitro pressure levels, and (4) its development is probably a long-term process.


A new colored soybean variety 'Jungmo3005' was developed as a breeding parent. 'Cheongjakong' and 'Geomjeongkong3' were crossed in 2000. F1 and F2 populations were grown for 2 years and selected by pedigree method from F3 to F5. The preliminary yield trial (PYT) and advanced yield trial (AYT) were conducted from 2006 to 2007, and regional yield trial (RYT) in 9 regions was conducted from 2008 to 2010. 'Jungmo3005' is determinate, white flower, green cotyledon, green spherical seed and yellow hilum. Flowering date and maturing date were July 30 and Oct. 7, respectively. Other quantitative characteristics of 'Jungmo3005' were similar to 'Cheongdu1', but it was more tolerant to lodging and shattering than 'Cheongdu1' at RYT field and indoor test. Although 'Jungmo3005' showed symptom of mosaic disease in inoculation test at greenhouse, it had high level of resistance to soybean mosaic virus and bacterial pustule diseases at field. The yield of tofu of 'Jungmo3005' was more than that of 'Cheongdu1'. The mean yield of 'Jungmo3005' in RYT was 256kg/10a which was 97% of the yield of 'Cheongdu1'. 'Jungmo3005' is expected to be widely used as a breeding parent to cross with other varieties and lines for creating colored soybean cultivars with tolerance to lodging, shattering and bacterial pustule.


Recent research identifies state capacity as a crucial determinant of civil peace. Scholars often interpret the association between wealth and peace as state capacity effects, but they have not clearly distinguished the impact of administrative reach and capacity for coercion from those effects that may capture good governance related to the provision of political goods and quality of institutions.We revisit the relationship between state capacity and civil peace by suggesting three different pathways through which the state avoids violent challenges to its authority: coercion, co-optation, and cooperation.We evaluate these three different notions of governing capacity both analytically and empirically, and we find that high levels of government spending on political goods and trustworthy institutions are more significant predictors of civil peace than are states' coercive capacities.The results suggest that civil peace is co-produced by social and state forces, where quasi-voluntary cooperation from society increases state capacity for maintaining peace.This is good news for policies aimed at building state capacity, since there seems to be room for agency beyond simply waiting for societies to become wealthy.


Anxiety disorders are more prevalent than any other mental health problem in the USA, but afflicted patients are often untreated or treated only by a primary care physician. Anxiety disorders can be understood in the context of the interplay of biological, psychosocial, and behavioral factors. Psychiatry has defined effective treatment that integrates education, psychotherapy and psychopharmacology. A combination of treatment approaches may be beneficial. Anxiety related symptoms, other than a true anxiety disorder, may be precipitated by normal stresses of daily life. These patients may also benefit from treatments used in anxiety disorders. Anxiety can also occur secondary to medical disorders and medications, as well as being present as part of other psychiatric syndromes. Diagnosis requires a history, physical examination and laboratory tests. Anxiety disorders, although common, are easily overlooked because patients may present with somatic complaints rather than admit to having emotional problems. Anxiety disorders are divided into seven categories in DSM IV, with each allowing for a differential treatment approach. Non‐pharmacological treatments are the first line of treatment, and may include behavior therapy and cognitive therapy. The physician‐patient relationship is itself a powerful treatment tool. Key areas in which the psychiatrist can help the patient cope are outlined. Benefits and risks of drug treatment for anxiety disorders are discussed.


Infection of protoplasts and spheroplasts by isolated bacteriophage DNA with production of whole phage has been reported for a number of organisms (Riggs & Rosenblum, 1969). This phenomenon has not previously been described in Proteus strains. DNA was prepared from phage 13 vir (Prozesky, de Klerk & Coetzee, 1965) by the technique of Gierer & Schramm (1956). The concentration of DNA, determined by optical extinction at 260 nm. (1 µg. DNA/ml. = 0.0205 absorbency units), ranged from 200 to 600 µg./ml. Sedimentation coefficients of the DNA at concentrations of 10 to 50 µg./ml. were determined in a Spinco model E ultracentrifuge (Rosenblum & Schumaker, 1963). The DNA was homogeneous and an average molecular weight of 26.3 × 106 was calculated. Sedimentation of the DNA through an alkaline sucrose gradient revealed no single-strand breaks.


QUESTIONS: Natural regeneration is increasingly recognized as a potentially cost‐effective strategy to reach ambitious forest landscape restoration targets, but rates of recovery are notoriously variable. We asked how well initial habitat conditions after cessation of agriculture predict forest recovery after nearly a decade. We aimed to provide land managers with general rules of thumb to assess when it is necessary to invest resources in active restoration, such as tree planting, to accelerate forest recovery. LOCATION: Coto Brus County, Puntarenas, Costa Rica. METHODS: We compiled data on initial vegetation structure, soil nutrients, prior land‐use history and surrounding forest cover at 13 sites. After 8.5 years, we measured vegetation indicators commonly used to assess forest recovery, namely amount of canopy closure and number and diversity of woody recruits. RESULTS: Two variables, grass cover and canopy closure, measured 1.5 years after site abandonment, explained 47–87% of five of the six response variables after 8.5 years; recovery was faster in sites with lower grass cover and higher canopy closure initially. Waiting an additional year to measure initial vegetation variables did not improve model fit. Time since the original forest was cleared explained 62% of change in canopy cover, whereas percentage of surrounding forest cover, length of pasture use and soil variables explained minimal additional variation. CONCLUSIONS: Our results suggest that two easily measurable vegetation variables can provide guidance to land managers and policy makers about where to invest scarce restoration resources to facilitate forest recovery.


An experimental investigation into model reference adaptive control of an electro-hydraulic servo-mechanism is reported. The servo-system consisted of a zero-lapped servo-valve and asymmetric actuator positioning a load of 890 kg. Parallel model reference adaptive control was employed with the desired level of system performance being specified in terms of a reference model transfer function. The performance of the basic scheme is enhanced by the introduction of a novel integral-action controller and typical performance characteristics with and without the controller are presented. The ability of the adaptive controller to maintain a consistent level of performance when subjected to a pseudo-random control signal is also discussed.


A prospective study was conducted in Awassa, Southern Ethiopia from July 1997 to April 1998 in order to determine the antimicrobial pattern of Shigella strains. Moreover, the study was intended to form the basis of treatment guidelines for shigellosis appropriate to local conditions. In addition, the study was designed to accumulate epidemiological information on the resistance patterns of Shigella isolates of public health importance. A total of one hundred Shigella strains were isolated from 289 cultures received at the Center for Health Research and Laboratories (CHRL), collected from different health units. Ninety-nine strains were Shigella flexneri group B and one Shigella dysenteriae group A isolated. All isolates were susceptibility tested for nine antibiotics using disc diffusion technique. The result showed that 96% and 90% strains were susceptible to gentamicin and nalidixic acid respectively. High rate of resistance was particularly documented against the following antibiotics: ampicillin (93%), erythromycin (90%), and tetracycline (90%). Fifty-six percent of Shigella flexneri Group B isolates were found to be resistant to trimethoprim-sulfamethoxazole, which is one of the drugs of choice for treating shigellosis is Ethiopia. Multiple drug resistance to as many as six antibiotics, i.e. ampicillin, cephalotin, chloramphenicol, erythromycin, tetracycline and trimethoprim-sulfamethoxazole has been observed in this study. One strain of Shigella flexneri was found to be resistant to eight drugs. The findings are discussed and recommendations forwarded.
(Ethiopian Journal of Health Development, 2000, 14(2): 149-154)


The vast amounts of data generated by scientific research pose enormous challenges for capturing, managing and processing this data. Many trials have been made in different projects (such as HNSciCloud and OCRE), but today, commercial cloud services do not yet play a major role in the production computing environments of the publicly funded research sector in Europe. Funded by the Next Generation Internet programme (NGI-Atlantic) from the EC, in partnership with the University California San Diego (UCSD), CERN is piloting the use of CloudBank in Europe. CloudBank has been developed by the UCSD, University of Washington and University of California, Berkeley with NSF grant support, to provide a set of managed services simplifying access to public cloud for research and education, via a cloud procurement partnership with Strategic Blue, a financial broker SME, specialised in cost management and optimisation. The European NGI experiment is provisioning cloud services from multiple vendors and deploying a series of use-cases in the domain of Machine Learning and HPCaaS, contributing to the scientific programme of the Large Hadron Collider. The main objective is to address technical, financial and legal challenges to determine whether CloudBank can be successfully used by Europe's research community as part of its global research activity.


Open access: http://isainsmedis.id/ Management of denture foreign body in esophagus with cervical esophagotomy: case report Kadek Yudi Fajar Mahendra1*, Ketut Putu Yasa2 Introduction: Impaction of dentures in the esophagus is a distressing experience for a patient and can lead to serious consequences, such as esophageal perforation. Patients with an impacted denture often present with a history of accidental swallowing, frequently during trauma, seizures, or sleep or in association with some degree of psychological dysfunction. The common signs and symptoms of an impacted denture are odynophagia, dysphagia, or simply pain and tenderness in the neck or chest.The preferred method of removal of esophageal foreign bodies is extraction with the flexible endoscope. Surgical removal is rarely indicated except in the event of perforation or other foreign body complications.In situations where this appears potentially hazardous, such as with impacted denture, open surgical extraction by cervical oesophagotomy is promptly performed is a safe option. Cases Report: The successful removal of impacted denture in the esophagus in a patient is reported, with a review of the literature. A women23-year-old complained of dysphagia after swallowing his denture. Following unsuccessful attempts at removal via a rigid esophagoscope, open surgery was performed. Without further delay, the impacted denture was removed by cervical oesophagotomy, and the patient recovered uneventfully. Conclusion: The successful removal of impacted denture by cervical oesophagotomy in the esophagus in a patient is reported. We conclude that cervical esophagotomy is a safe method for removing foreign bodies impacted in the cervical esophagus when they cannot be removed endoscopically.


Atorvastatin (Lipitor™) is a lipid‑lowering agent that is widely used in the treatment of cardiovascular diseases. Previous research has largely focused on its cholesterol‑lowering effects; however, a limited number of studies have investigated the actions of atorvastatin on vascular endothelial cells. In the present study, the effects of various doses of atorvastatin were investigated on human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of atorvastatin in serum‑free or serum‑containing medium, and alterations in HUVEC morphology were observed. Cell survival and necrosis rates were evaluated using sulforhodamine B and lactate dehydrogenase assays, respectively. In addition, the protein expression levels of cellular apoptosis and autophagy markers were detected using western blot analysis. The results revealed that HUVEC morphology was altered following treatment with various concentrations of atorvastatin. In addition, autophagy was demonstrated to be induced by atorvastatin treatment at all concentrations, whereas high concentrations appeared to induce apoptosis and suppress the survival of HUVECs. In conclusion, the results of the present study suggested that various doses of atorvastatin may exert differential effects on HUVECs, and high doses may suppress angiogenesis. Therefore, atorvastatin may present a novel potential anti‑tumor therapeutic strategy. However, further studies are required to fully elucidate the association between the dose of atorvastatin and its clinical outcome.


This paper provides an empirical analysis of Colombian integration with East Asia using a Computable General Equilibrium (CGE) model, in which we assess the effects of several trade liberalization scenarios on trade flows and welfare. The results show that there is an important potential for the development of Colombian exports of other crops, chemical products, apparel and textiles to East Asian nations. This result is not derived from subscribing a Free Trade Agreement, but from unilaterally liberalizing tariffs in both regions.


The rocks along the southeast flank of the Bighorn Mountains range from Precambrian to Quaternary, but include no Ordovician, Silurian, or Devonian. Two Jurassic formations characteristic of central Wyoming, the Nugget sandstone and Gypsum Spring formation, are lacking. Tertiary deposits are present along the southern margin and at places higher in the mountains. The top of the Middle Cambrian Flathead sandstone makes an upward migration in time toward the northeast of 22 feet per mile. The Upper Cambrian Du Noir member of the Gallatin formation tongues out eastward within the area. The presence of remnants of the basal Phosphoria Nowood member implies early Permian deposition and erosion prior to deposition of younger Phosphoria strata. Eastward-extending dolomite and limestone Phosphoria tongues alternate with westward-extending red shale tongues. A restricted use of the name Crow Mountain sandstone member is applied to the Triassic Chugwater interval between the Alcova and the Popo Agie members. A high-angle reverse fault in the southern part of the area is probably related to the southward thrusting of the Bighorn Mountains during the earliest Eocene. Intense faulting in Mesozoic rocks at the southern margin of the mountains suggests proximity to a main thrust zone covered by younger Tertiary deposits. Northwest-trending folds and faults probably developed later than the thrust faulting. Five oil tests, including two within the area, are dry holes. Four of these tests had oil staining in the Phosphoria; one had staining in the Tensleep. A gentle dome in the southeastern part of the area has not yet been tested.


The question of the legal nature and the binding nature of explanations of the Supreme Court of the Russian Federation remains debatable in the literature. When considering criminal cases, the courts do not always follow the decisions of the Plenum of the Supreme Court. It seems that the explanations of the Supreme Court, while not being a source of criminal law, are nevertheless binding on courts and officials applying the norms of criminal law. This is a general rule, to which there are exceptions. First, there are erroneous explanations of the Supreme Court, which are not based on the established judicial practice and are not supported by it. Second, there are outdated explanations of the Supreme Court that do not meet modern legal realities. Third, there are explanations of the Supreme Court, which, in relation to a particular situation, require an expansive or restrictive interpretation. In these three situations, the Supreme Court's explanations do not bind the law enforcement officer. The binding nature of the Supreme Court's explanations is determined by the value of the law as such. Questions of law require a uniform resolution. An alternative to a uniform interpretation of the law is arbitrary administration. Arbitrary administration is not within the competence of the judge. There is no case law in Russia. The works of legal scholars in modern Russia also cannot satisfy the need for a uniform interpretation of the law. The significance of the explanations of the Supreme Court determines the high requirements for their quality. The Supreme Court's explanations should not directly contradict the law. The Supreme Court's explanations should not change unless there is an urgent need to do so. The rule nullum crimen, nulla poena sine lege, being an achievement of legal culture, binds the Supreme Court. By clarifying the practice of applying the law, the Supreme Court forms and preserves judicial doctrine, thereby providing legal certainty.


BACKGROUND
Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort.

METHODS
Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected and isolates underwent whole genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBL) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture.

RESULTS
Of the 114 CP-Ec isolates in CRACKLE-2, 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine source (49% vs. 29%), less often met criteria for infection (39% vs 58%, p=0.04), and had lower acuity of illness when compared to non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared to non-MBL-Ec was 62% [95% CI: 48.2, 74.3]. Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; p=0.02) and 90-day (39% vs 0%, p=0.001) mortality compared with MBL-Ec.

CONCLUSION
Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.


Manufacturing companies are companies that produce raw goods into finished goods, one of which is the  consumer goods industry. The consumer goods industry is an industry that society needs to produce products for daily needs. Therefore, investors continue to look at the shares of this industry because they are considered to be always stable in determining the level of profit production. The purpose of this study is to understand the factors that influence stock returns with profitability as an intervening variable. The data used are secondary data collected from the Indonesia Stock Exchange 2014-2018 publications. The data processing method uses the path analysis method with IBM SPSS version 22. The results of the study show that Earnings Per Share and Debt Adequacy Ratio are related to Profitability. Yield Dividend, Firm Size, and Growth does not affect Profitability. Growth concerns Stock Returns, but Company Size, Dividend Results, Firm Size and Profitability Adequacy Ratio can be intervening variables Earning Per Share, but Profitability is not able to become intervening variables such as Yield Dividend, Company Size, Growth and Debt Adequacy Ratio.


The transgenic tobacco plants transformed with movement protein gene of Tomato mosaic virus (ToMV) or Tobacco mosaic virus (TMV) and partial replicase gene of Cucumber mosaic virus (CMV) P1 isolate (CMV-P1), were inoculated with Potato virus X, Potato virus Y, TMV and CMV isolate RB (CMV-RB), respectively. Symptom observation showed there were no symptom differences in transgenic tobacco plants as compared with those in non-transgenie tobacco plants. ELISA also illustrated that the virus concentrations in the transgenic plants were similar to those in non-transgenic plants, indicating that no synergism is found in these plants. The transgenic tobacco plants expressing movement protein gene of ToMV or partial replicase gene of CMV-P1 were inoculated with TMV and CMV-RB, respectively. The local or systemic infected leaves were then used for elucidation of the possible virus recombination in transgenic plants with biological infectivity test, ELISA and immuno-capture RT-PCR. Within 16 months, no recombination was found between transformed genes and inoculated virus genomes. The research provides fundamental data for understanding of the possible risk of the transgenic plants expressing viral sequences.


The enzyme-linked immunosorbent assay (ELISA)-inhibition test using a Clonorchis sinensis species-specific mouse monoclonal antibody (MAb), CsHyb 0605-23, showed increased specificity over the conventional ELISA used for serodiagnosis of clonorchiasis. To characterize the corresponding antigen further, the MAb was tested against polysaccharide, protein and glycolipid fractions obtained from a crude extract of C. sinensis adult worms, using chloroform, methanol and phenol extractions. Only the polysaccharide fraction was recognized by the MAb among those fractions. Mild oxidation of the antigen with sodium periodate showed decreased reactivity against the MAb. We concluded that the antigen and antigenic determinants recognized by the MAb are carbohydrates.


The paper deals with a switching performance optimal control for continuous-time controller switched systems. Steady-state bumpless switching is considered. An linear matrix inequality (LMI) based static bumpless switching compensator design is given via internal model principle, guaranteed cost and regional pole placement technique. The corresponding bumpless switching scheme is also presented. The proposed scheme is simple in structure, and easy to be implemented. Simulations for the generic hypersonic vehicle model show the effectiveness of the proposed method.


A series of economic and transformational crises in Latin America during the 1990s and the early 2000s pushed many households into poverty. In this paper we look at the two most significant of those crises that took place in Mexico and Argentina and explore the policy measures that were put in place to mitigate their impact on the economy and more importantly, on the population. For this purpose, the analysis looks at a series of transmission channels form economic shocks through the macro to the meso-level, the effects of these impacts on households and their behaviour, and more specifically on children. The paper sheds some light on the different angles through which the current (and future) crisis might affect individuals, particularly children. More importantly, the paper draws out some lessons learned from the effective and ineffective policy responses put in place almost ten years ago, which can be relevant to infom decision makers dealing with policy responses to mitigate the impact of poverty and vulnerability in the wake of the current crisis.


This paper discusses application of hyperspace data mining to materials manufacturing. We introduce an innovative hyperspace method whereby data are separated into subspaces, features selected according to data patterns, and control rendered in the original feature space. This technique has three major advantages: no equipment is added, no experiment is needed, and no interruption occurs to production. A number of proprietary algorithms have been built into a software product, MasterMiner/sup TM/, for use in materials design and manufacturing. Examples are given to show the efficacy of the proposed method and MasterMiner tool.


Despite the lingering stereotype, computer science and programming has long abandoned the development model consisting of a lone programmer writing code into the early hours of the morning. There may be aspects of this heroism in a product development cycle, particularly when close to a release date, however to bring a software product to market requires collaboration within a team of programmers. Developing software products, as opposed to simply programming, is a social process. We believe that learners gain a greater understanding of the software development process through social interaction with other developers. Such beliefs are consistent with the General Genetic Law of Cultural Development proposed by Lev S. Vygotsky. We consider Free and Open Source software development to be a readily available repository of differing development processes to use in introducing learners to the social side of software development. The contribution of this paper is to introduce and expand upon a vocabulary for discussing Source and Configuration Management tools in a Vygotskyian context.


The human MAT1 gene (ménage à trois 1) is an assembly factor and a targeting subunit of cyclin-dependent kinase (CDK)-activating kinase. The novel mechanisms by which MAT1 forms an active CDK-activating kinase and determines substrate specificity of CDK7-cyclin H are involved in the cell cycle, DNA repair, and transcription. Hyperplasia of vascular smooth muscle cells (SMC) is a fundamental pathologic feature of luminal narrowing in vascular occlusive diseases, and nothing is yet known regarding the cell cycle phase specificity of theMAT1 gene in its involvement in SMC proliferation. To investigate such novel regulatory pathways, MAT1 expression was abrogated by retrovirus-mediated gene transfer of antisenseMAT1 RNA in cultured rat aortic SMCs. We show that abrogation of MAT1 expression retards SMC proliferation and inhibits cell activation from a nonproliferative state. Furthermore, we have demonstrated that these effects are due to G1 phase arrest and apoptotic cell death. Our studies indicate a link between cell cycle control and apoptosis and reveal a potential mechanism for coupling the regulation of MAT1 with G1 exit and prevention of apoptosis.


A large circular e+e− collider followed by a highest-energy hadron collider in the same tunnel promises the most far-reaching physics program for the post-LHC era, and such a facility could well serve the particle physics community through the end of the 21st century. Two such projects are presently proposed: The Future Circular Collider, in a global collaboration hosted by CERN, and the combination of Circular Electron Positron Collider and Super Proton-Proton Collider, advanced by IHEP Beijing. Over the centre-of-mass energy range from 90 to about 365 GeV, covering all known heavy elements of the Standard Model, from the Z resonance to the top-quark threshold, the circular e+e− collider offers a high luminosity and exquisite energy efficiency. The high luminosity is maintained by top-up injection from a full-energy booster synchrotron. On the Z pole and at the WW threshold resonant depolarisation will allow for a precision energy calibration at the ppm level. This article summarizes and compares the designs of FCC-ee and CEPC, covering the latest accelerator layouts and beam parameters, R&D plans, ongoing prototyping of key technologies, such as for the SRF system, and possible implementation schedules.


Abstract Soviet wartime propaganda and contemporary Russian work on the activities of the Orthodox Church during the war promote the Church's claim that it was motivated by patriotism, a point it used to claim legitimacy in the USSR and now in contemporary Russia. In contrast, this paper argues that the hierarchs and laity of the Patriarchal Church were not essentially motivated by patriotism or the desire to show loyalty to the Soviet regime in 1941, but instead acted to use the war to achieve three goals: first and most important, to become relevant in the everyday life of the Soviet people by promoting Christian beliefs and values; second, to earn legitimacy in the eyes of anti-clerics and non-believers by lending moral and practical support to the war effort; and finally, to obtain legal standing by showing its trustworthiness and loyalty through displays of Russian (not Soviet) patriotism consonant with its historic role, all the while without endorsing communist ideology. The hierarchs orchestrated a campaign from the top down throughout the clerical hierarchy, to achieve the aforementioned goals whilst from below the faithful, independently of the hierarchs, used their local displays of patriotism as leverage to reopen local churches and to force the regime to respect their right to worship. The grassroots response by believers and parish clerics in support of the Church and its wartime activities represents primarily an endorsement of the Church, Christianity, Russian patriotism, and only secondarily, if at all, loyalty to the Stalinist regime.


CONTEXT
Lipodystrophy syndromes are rare disorders characterized by the selective loss of adipose tissue. We aimed to report a case of acquired generalized lipodystrophy possibly associated with nivolumab.

CASE DESCRIPTION
A woman was referred to our Endocrinology Department for uncontrolled diabetes mellitus. At 50 years of age, she was diagnosed with type 2 diabetes after a routine laboratory test and her diabetes was well controlled with low doses of metformin. In 2010, she was diagnosed with clear cell renal carcinoma. The cancer progressed in the following years, leading to the initiation of treatment with nivolumab in 2017. Two months later she presented with facial lipoatrophy, with loss of the buccal fat pads and prominent zygomatic arch. Her neck, shoulders, arms, and buttocks were also affected. Her diabetes control worsened. She received maximal doses of metformin and pioglitazone and was administered 1.5 units/kg/d insulin. Subcutaneous biopsy of medial surface of the arm revealed chronic lobular panniculitis. Despite nivolumab's possible involvement in the onset of lipodystrophy, the maintenance of nivolumab therapy was justified by the observed reduction in the progression of the cancer, combined with the lack of an alternative chemotherapy. The therapy was withdrawn after 8 months of treatment because of grade 3 hepatitis.

CONCLUSION
Anti-PD1 therapy has great potential. Early recognition of the onset of unusual collateral effects is important to improve decision making regarding the treatment of patients with tumors.


Tissue-engineered vascular grafts (TEVGs) have emerged as a potential alternative to autologous grafts for replacing small-diameter blood vessels during bypass surgery. The axial alignment of endothelial cells (ECs) and the circumferential alignment of smooth muscle cells (SMCs) are crucial for functional native blood vessels (NBVs). However, achieving this cellular alignment in TEVGs remains a formidable challenge. In this study, TEVGs were developed using a low-cost technique that aligned ECs axially and SMCs circumferentially within hours. The TEVGs comprised an electrospun polycaprolactone (PCL) layer and a gelatin methacryloyl (GelMA) cast layer. A freezing-induced alignment technique was developed that partially aligns the electrospun fibers axially, thereby promoting rapid axial alignment of ECs. Furthermore, SMCs cultured in a GelMA layer with intermediate stiffness (5-12 kPa) surrounding a PCL tube could promote conformation of the SMCs to the curvature of the PCL tube, resulting in their spontaneous circumferential alignment. Additionally, the TEVGs demonstrated mechanical properties similar to those of NBVs, which could facilitate future translation. This approach represents a significant advance in tissue engineering, enabling the fabrication of TEVGs with appropriate mechanical properties that recapitulate key NBV cell structural features within hours using a scalable and accessible method.


Results of scanning tunnelling microscopy (STM) show that two different kinds of surface structures coexist on the (110) surface of Pt80Fe20. The predominant structure corresponds well to the missing row type (1*2) reconstruction previously observed on, for example Pt(110), whereas the minority domains show a faintly buckled structure with approximately (1*1) geometry. Based on the STM images, the authors propose that the two domains have different surface chemical compositions and correspond to two different metallurgical phases known for the PtFe system at this composition.


We study classical and quantum scattering in periodically driven mesoscopic electronic devices. The ac-driven square potential well, a prototypical example, is shown to be a chaotic scatterer. Quantum transport in the nonlinear regime of strong driving is investigated in the Floquet framework. In the deep quantum regime, scattering into and out of bound states of an effective potential explains most of the structure in reflection, transmission, and dwell time, controllable via the external driving. For large amplitude and frequency, a single ac-driven quantum well exhibits dynamical tunneling. We identify signatures of the classical phase-space structure in Wigner-function representations of propagated wavepackets.


Abstract Few studies of the transition to adulthood in Africa analyse young people's own definitions of the events that confer adult status, and how adulthood is actually attained. This paper examines the experience of transitioning to womanhood in rural Mpumalanga Province, South Africa, drawing on interviews with 18 women aged 18–39. Three primary experiences characterised this transition: puberty and emerging body awareness, spending time with boys, and having a child. More important than the timing of these experiences, however, was whether women 'behaved well' and maintained respectability as they transitioned to adulthood. Behavioural standards reinforcing ideal femininity were focused on dress, manner and talk, and were particularly stringent for mothers. Findings emphasise the value of emic models of adulthood for understanding how youth experience this transition and provide an important counter-narrative to the literature focused primarily on the risk African youth face during this period of change in the life course.


The green industry comprises the production and marketing of woody ornamentals, greenhouse, and turfgrass-related products, and landscape and horticultural services. The industry is market oriented with prospects for future growth. Many state trade organizations have become interested in better measurement of the industry's economic contribution. The contribution of major industry sectors to the Louisiana economy are quantified with a state input-output model. Also presented are study results that are mainly based on readily available data sources. Results suggest that the state industry made a strong contribution to economic activity comparable in size to that of other major agricultural commodities.


In the aftermath of the contested Romanian anti-communist revolution of December 1989, the National Salvation Front (NSF), led by Ion Iliescu, emerged as the country's provisional government. Amidst increasing suspicions of the revolution having been a strategic coup d'etat orchestrated by the neo-communist NSF, in June 1990, protesters gathered in Bucharest's University Square demanding the removal of the NSF government. To maintain the narrative rationality of the story of an authentic revolution, and to thus legitimize his claim to power, Iliescu employed a set of rhetorical tactics meant to reaffirm his commitment to democracy and to antagonize the emergent sphere of civic activism, while simultaneously reigniting deeply-entrenched class struggles. Through his political discourse, Iliescu managed to shift public perceptions of democracy, legality, and moral purity, by reframing unconstitutional measures, employing the redemptive rhetoric of revolutionary heroism, and strategically using the familiarity of communist rhetoric to ensure the public's continued alle-


In this paper, the specific details of a 4-storey, 3-bay reinforced concrete frame test structure with unreinforced brick masonry (URM) infill walls are described along with estimates of its likely weaknesses with regard to seismic loading. The construction details for this building are typical of construction more than 40 years old in Mediterranean European countries. The concrete frame is shown to be essentially a "weak-column strong-beam frame" which is likely to exhibit poor postyield hysteretic behaviour. Based on the results of an extensive literature review, the building is expected to have maximum lateral deformation capacities corresponding to about 2% lateral drift. The unreinforced masonry infill walls are likely to begin cracking at much smaller lateral drifts, of the order of 0.3%, and to completely lose their load carrying ability by drifts of between 1% and 2%. Three seismic retrofit schemes were identified, based on the literature review, for further study. The effectiveness of each retrofit scheme will be tested using full-scale pseudo-dynamic tests at the European Laboratory for Structural Assessment (ELSA) at the European Commission's Joint Research Centre in Ispra, Italy. The results of the detailed analyses and tests will be reported elsewhere.


The sociology of homosexuality lacks engagement with queer theory and postcolonialism and focuses primarily on the global metropoles, thus failing to provide a plausible account of non-Western non-normative sexual identities. This research adopts the author's newly proposed transnational queer sociology to address these deficiencies. First, it critiques the Western model of sexual identity predominantly employed to elucidate non-Western, non-normative sexualities. It does so by examining not only the queer flows between West and non-West but also those among and within non-Western contexts to produce translocally shared and mutually referenced experiences. Second, the proposed approach combines sociology with queer theory by emphasizing the significant role of material, as well as discursive, analyses in shaping queer identities, desires and practices. This article employs the approach to examine young gay male identities, as revealed in 90 in-depth interviews conducted in Hong Kong (n = 30), Taiwan (Taipei, n = 30) and mainland China (Shanghai, n = 30) between 2017 and 2019. More specifically, it highlights the interplay between the state and identity by investigating the intersection and intertwining effects of these young men's sexual and cultural/national identities, revealing three different forms of civic-political activism. The article both demonstrates the way in which sexuality and the state are mutually constituted and provides nuanced analysis of the heterogeneity of contemporary homosexualities in Hong Kong, Taiwan and mainland China. In applying a new sociological approach to understanding sexuality, this research joins the growing body of scholarship within sociology that is decentring the Western formation of universal knowledge.


Higher blood pressure variability (BPV) is associated with poor functional outcome and mortality in acute stroke. This randomized controlled trial was conducted to compare the effect on BPV between fimasartan and valsartan (Boryung Pharmaceutical Co., Ltd., Seoul, Republic of Korea) in patients with acute ischemic stroke. Eighty patients were randomly assigned to receive either valsartan or fimasartan after 7 days of acute ischemic stroke onset, for duration of 8 weeks. Of them, 62 patients completed the study [valsartan (n=31), fimasartan (n=31)]. We measured BP for 24 hours using ambulatory BP monitoring device before and after 8 weeks of starting BP medication. We calculated several indexes such as standard deviation (SD), weighted 24-hour BP with SD (wSD), coefficient of variation (CV), and average real variability (ARV) to assess BPV and to compare indexes of BPV between 2 drugs. SD values of systolic BP in daytime, nighttime, and 24 h period (15.55±4.02 versus 20.55±8.77, P=0.006; 11.98±5.52 versus 16.47±6.94, P=0.007; 17.22±5.30 versus 21.45±8.51, P=0.024), wSD of systolic BP (8.27±3.01 versus 10.77±4.18, P=0.010), and ARV of systolic BP (15.85±6.17 versus 19.68±7.83, P=0.040) of patients receiving fimasartan after 8 weeks were significantly lower than patients receiving valsartan. In paired t-test, SD values of daytime, nighttime, and 24 h period of systolic BP of patients receiving fimasartan were significantly decreased after 8 weeks (15.55±4.02 versus 18.70±7.04, P=0.038; 11.98±5.52 versus 17.19±7.35, P=0.006; 17.22±5.30 versus 20.59±5.91, P=0.015). Our study showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan. Trials registry number is KCT0003254.


Abstract In today's multicultural society, intercultural competence has become a critical component of the health educator's skill portfolio. This competency is required for understanding ourselves and others from different cultures, managing relationships, developing and implementing programs that match the needs of target audiences, and integrating our insights as educators into larger political and economic institutions. Intercultural competence requires knowledge of culture theory; awareness of the impact of culture on health beliefs, health behaviors, and learning styles; and a willingness to change behavior in ways that promote cultural synergy. Health educators can improve their intercultural competence by studying culture theory; participating in cross-cultural simulations; developing insights into the behavior of individuals and groups experiencing cross-cultural tensions; developing personal strategies for responding to cross-cultural conflicts; expanding opportunities to interact with individua...


The operation On 17 August 2006, Atlas Copco AB, a world leader in compressors, generators, construction and mining equipment, industrial tools, assembly systems and equipment rental, notified…


Shoveler breeding and bred in Great Britain tend to move south in autumn and winter, some travelling as far as south-west Spain, the Camargue and central Italy. Few seem to be wholly sedentary. No clear case of abmigration has been found. Ringing in autumn and winter in southern England and Wales reveals differences in the movements of Shoveler caught from August to October and those caught from November to February. While recoveries in winter of birds from both groups show a mainly southerly scatter like that of the breeding birds, the winter-ringed birds have provided a relatively large proportion of recoveries around the Baltic and east into the U.S.S.R. This suggests that winter visitors and passage-migrants from the north-east tend to arrive in England quite late, Shoveler are probably most numerous in England in March, but hardly any have been ringed at that time so that the movements of these late-winter and spring visitors are not yet understood.


Music's 'malleability' (Taylor 1997) has always facilitated its export and import from one location to another. Indeed, such processes are central to the creation and dissemination of new musical forms. Yet in our contemporary globalised world, such processes occur ever more extensively and rapidly giving rise to new forms of appropriation and syncretism. Record companies from the developed world find new audiences in the developing world (Laing 1986). Musicians from the West appropriate non-Western music, sometimes collaboratively (Feld 1994; Taylor 1997). Non-Western musicians and musicians from subaltern groups within the West create new syncretic forms drawing on both Western and non-Western music (Mitchell 1996; Lipsitz 1994, Slobin 1993). The resulting 'global ecumene' produces considerable 'cultural disorder' (Featherstone 1990, p. 6) whose results cannot easily be summarised.


Background: Excess amounts of lead in serum may affect different organ systems and cause lead poisoning. This toxicity mostly happens in chronic and occupational settings. This report comprises the clinical presentation of an acute case of lead toxicity with a much uncommon source of poisoning: opium. Case Presentation: A 25 year old man was presented to us with abdominal pain, nausea and vomiting, severe weight loss, generalized bone pain, and jaundice. He had six years history of addiction to oral and inhalation forms of opium. Pallor and jaundice were observed in his mucosa and bluish pigmentation was evident at the gum-teeth line. Hepatosplenomegaly and lymphadenopathy were not detected. Upper GI endoscopy was normal. Liver enzymes and indirect billirubin were increased; however, alkaline phosphatase was in normal range. Laboratory tests were indicative of hemolytic anemia without autoimmune origin.  Bone marrow aspiration and biopsy were indicative of erythroid hyperplasia. According to the symptoms and the clinical symptoms of lead poisoning, the lead level was measured both in the serum and in the opium sample the patient used to use. 350mcg/dl of lead in the serum and the very high lead content of the opium sample confirmed the diagnosis; therefore, patient was treated with Calcium-EDTA and BAL that caused decrease of lead level and elimination of symptoms.


To determine the nature of the resultant effect on blood pressure when angiotensin converting enzyme (ACE) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension, two randomized, double-blind, crossover trials were conducted. In each trial there were four treatment phases, each 4 weeks in duration, comprising a 2 X 2 factorial experiment. Twenty-one patients completed the first study in which the effects of enalapril (10 mg twice daily) were compared with hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo. All blood pressure parameters were reduced in the three active treatment phases compared with placebo (P less than 0.001). Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive. Sixteen patients completed the second study which compared the effects of enalapril (20 mg daily), atenolol (50 mg daily), the two drugs in combination and placebo. All blood pressure parameters were again reduced in all phases compared with placebo (P less than 0.001). Enalapril and atenolol were also equally effective, but in combination their hypotensive effects were less than fully additive, with attenuation of the potential additive response by 30-50%. These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination. Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide (ANP) concentrations (P less than 0.01), suggesting that ANP could contribute to the hypotensive effects of these two drug classes.


Facial expression recognition is a challenging task when neural network is applied to pattern recognition. Most of the current recognition research is based on single source facial data, which generally has the disadvantages of low accuracy and low robustness. In this paper, a neural network algorithm of facial expression recognition based on multimodal data fusion is proposed. The algorithm is based on the multimodal data, and it takes the facial image, the histogram of oriented gradient of the image and the facial landmarks as the input, and establishes CNN, LNN and HNN three sub neural networks to extract data features, using multimodal data feature fusion mechanism to improve the accuracy of facial expression recognition. Experimental results show that, benefiting by the complementarity of multimodal data, the algorithm has a great improvement in accuracy, robustness and detection speed compared with the traditional facial expression recognition algorithm. Especially in the case of partial occlusion, illumination and head posture transformation, the algorithm also shows a high confidence.


It sounds innocuous compared to war, plague and famine, but flu is actually one of the world's biggest killers. Since the first documented pandemic of an influenza-like disease in 1580, 31 worldwide influenza outbreaks have been recorded, culminating in the pandemic of 1918 that killed an estimated 50 million.This fascinating book explores the havoc caused by the world's most deadly virus - and the destruction left behind in its wake. From its initial identification by the Greek physician Hippocrates in the 4th century BC to the Spanish flu pandemic of 1918, the author explores the social, medical and scientific ramifications of the major outbreaks that have occurred over the centuries - and the potential ramifications should such a pandemic occur in the modern world.The likelihood and consequences of a pandemic occurring in the event of the highly pathogenic H5N1 strain of avian flu jumping species is also explored, along with recent scientific attempts to alter the structure of the virus in order to destroy it or ameliorate its virulence.


Multidrug resistant variants of two human osteosarcoma cell lines (U-2 OS and Saos-2) were selected by continuous exposure to doxorubicin. The in vitro and in vivo growth characteristics of these sublines as well as the expression of osteoblastic markers and of some surface antigens were analyzed. Resistant variants showed a higher doubling time and a lower cloning efficiency, and a lower metastatic ability after i.v. injection than corresponding parental cell lines. All the sublines showed overexpression of p-glycoprotein (referred to as p170). The level of expression of this protein in the different cell lines was directly related to the degree of resistance as shown by the in vitro sensitivity to doxorubicin and other multidrug-related drugs. In sublines showing the highest levels of resistance (over 300-fold), p170 overexpression was associated with mdr 1 gene amplification. These are the first multidrug resistant human osteosarcoma cell lines ever reported. They may be used as a model for further investigations into the mechanisms of drug resistance in osteosarcoma and as a standard for the assessment of chemosensitivity in clinical samples.


Introduction: Anaplastic thyroid cancer (ATC) is a rare refractory disease, found in 1-3% of thyroid cancer. Because of its highly malignant potential, patients often become lethal within 6 months, nevertheless for intensive multimodal therapies. Recent observations indicated the strong efficacy of multi-kinase inhibitor to control disease progression of ATC. Frequent BRAF mutation (40-60%) in tumors of ATC was reported in Japan, indicating BRAF gene alteration as possible molecular target. Moreover, the secretions of VEGF were often found in ATC cell lines, suggesting the important role of VEGF-mediated tumor neo-vascularization in the aggressive progression of ATC. We, thus, examined the antitumor effect of Sorafenib, a multi-kinase inhibitor demonstrating its effect by inhibiting both BRAF and VEGF signal. Materials & Methods: Human ATC cell lines having four different gene mutations were used (OCUT-4; BRAF mutation, OCUT-6, ACT-1; NRAS mutation, OCUT-2; BRAS and PI3KCA mutation). The effect of Sorafenib on cellular viability was evaluated by MTT assay. In order to investigate the mechanism of cellular damage by Sorafenib, cell cycle was evaluated by flowcytometry, and the signal transduction of RAF/MEK pathway was examined by Western blotting. The amount of VEGF secretion from cells was measured by ELISA. Expression of VEGF-receptor in cells was evaluated by Western blotting. Furthermore, the effects of Sorafenib on human vascular endothelial cells were investigated by recruiting HUVEC (Kurabo, Japan) stimulated with VEGF and conditioned medium of the cancer cells. Results: The effect of Sorafenib appears most strongly in OCUT-4 cell with BRAF mutation compared with other cell lines. However, the impairment of cellular viability was shown at relatively high concentration (>100 nM). OCUT-4 showed G1 phase arrest by Sorafenib exposure. The specific effect of BRAF inhibition was confirmed by the suppression of MEK and ERK phosphorylation in OCUT-4. The suppression was not observed in OCUT-6, a cell line with NRAS mutation. The paradoxical increase of MEK phosphorylation was found in this cell line, instead. Every cell line secreted different amount of VEGF, and the proliferation of HUVEC was stimulated by their conditioned mediums similarly as by VEGF. The stimulation of proliferation was suppressed both by anti-VEGF antibody and Sorafenib. Discussion: In the present study, we clearly demonstrated that Sorafenib inhibits growth of human vascular endothelium mediated by VEGF secretion from cancer cells, as well as direct cell cycle arrest on ATC cells. A high concentration of Sorafenib may be needed to show inhibition on the RAF/MEK pathway. Furthermore, the inhibition of the pathway was not effective when additional growth stimulatory pathway than RAF was activated as in case of OCUT-2, or RAS gene were mutated. However, in any case, cancer cell growth mediated by autocrine system was inhibited clearly by Sorafenib. Citation Format: SAE ISHIHARA. Mechanism of antitumor effect of Sorafenib in anaplastic thyroid cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1025.