A computational study using a hybrid DFT method (M06) on the cyclopropanation of endo-dicyclopentadiene with Simmons-Smith zinc carbenoids is reported. Each channel proceeds via the methylene-transfer mechanism with a reactant complex (RC) and subsquently a asynchronous transition state (TS). The channels with monomeric IZnCH(2)I attacking the double bonds from the exo-face have a much lower barrier (about 16.17-18.43 kcal/mol) in the gas phase, compared with the channels from the endo-face (21.80-31.13 kcal/mol). Thus, P1 and P3 are the primary cyclopropanated compounds, and P5 is the sole final product, representing remarkable stereospecificity. When considering the bulk solvent effect of diethyl ether, the barriers are decreased about 0.50-7.77 kcal/mol due to more "destabilization" of RC than TS. The solvated (ICH(2))(2)Zn can further reduce the barriers about 0.18-2.30 kcal/mol. In addition, the solvated IZnCH(2)I and (ICH(2))(2)Zn do not change the reaction pathways and retain the stereospecificity. Our computational results agree with the experimental observations quite well and suggest that both IZnCH(2)I and (ICH(2))(2)Zn might be the active species in the real reaction system. Regarding the solvent effect, the polar continuum model is more realistic than the direct involvement of diethyl ether molecules.


The method of self-propagating high-temperature synthesis of submicron powders with subsequent vacuum sintering was used to produce a series of optical ceramics based on dysprosium oxide (DyxY0.95-xLa0.05)2O3, where x=0.7, 0.85, and 0.9. The influence of ceramics composition on optical transmission of the obtained samples was investigated. The studied materials had several transparency windows in the visible 500-730 nm, near-IR 1900-2300 nm, and mid-IR 3500-7500 nm ranges. The dependence of the Verdet constant on wavelength in the 400-1940 nm range was measured for each ceramics composition, and analytical approximations were obtained. When Y and La dopants were used, the Verdet constant depended linearly on the concentration of Dy3+ ions, and its value in the visible wavelength range was about twice that of the analogous value for a terbium gallium garnet crystal. The high transmission and relatively high Verdet constant make the produced materials highly promising for fabricating Faraday devices for Tm3+ and Ho3+ lasers and for lasers emitting in the visible spectrum.


This document is the EUROCONTROL Specification, developed under the EUROCONTROL Regulatory and Advisory Framework (ERAF), for Aeronautical Information Exchange (AIX). It enables the standardised encoding and the distribution in digital format of the aeronautical information/data that is in the scope of Aeronautical Data Quality (ADQ) Regulation (EU) 73/2010, developed in accordance with the interoperability Regulation in the framework of the Single European Sky (SES). The Specification also sets out the use of the Aeronautical Information Exchange Model (AIXM) complying with requirements listed in the document.


Abstract The present paper considers the problem of selecting a set of high representative laboratory experiments among an important number of already executed ones, to build a model which can be used to guide the production efficiency maximization of a biochemical production process. This problem was identified in the context of the research for an efficiency system production of a biochemical product. The main idea is to take, from a large number of realized laboratory experiments, the most representative data to model the system with a mathematical formulation. It must include the more influent factors on the production efficiency. This model can be taken to identifies a theoretical near optimal production conditions in order to maximize the production efficiency. Experimental data are obtained from several experiments that were conducted on the research laboratory. Data are accrued historically since the research was concentrated on the efficiency increasing, but never a global analysis has been performed for this real case. The conducted experiments were not orthogonally designed. To select the experiments, given the fact that the system can be altered by many factors, a metaheuristic method was employed.


The photoelectron spectrum of sulphur trioxide has been recorded and extensive fine structure resolved. In three bands of the spectrum there is evidence for Jahn-Teller distortion. This has been interpreted quantitatively using the model of Longuet-Higgins, Opik, Pryce & Sack (1958). It also provides definite evidence that the three bands correspond to degenerate electronic states of SO+3. Four ionization potentials were found with values 12.8, 13.8, 14.9 and 17.9 eV. In two cases approximate changes in the S—O bond length have been calculated from the experimental data. The order of the first three electronic states of SO+3 is unexpected, the ground state being degenerate. This result is compared with other data from photoelectron, ultraviolet and electron spin resonance spectra of isoelectronic species.


The impact of the South China Sea summer monsoon (SCSSM) on the Indian Ocean dipole (IOD) has been systematically investigated in observations. This study focuses on the ability of climatemodels participating in phase 5 of the Coupled Model Intercomparison Project (CMIP5) to reproduce the observed relationship between the SCSSM and IOD and the relevant physical mechanisms. All 23 models reproduce significant correlations between the SCSSM and IOD during boreal summer [June–August (JJA)], whereas the influence of the SCSSMon the IOD varies considerably across the CMIP5 models. To explore the causes, all models are divided into two groups. Models that successfully simulated both the correlations between the SCSSM and JJA IOD and of the SCSSM and JJA IOD with precipitation over the western North Pacific and Maritime Continent are classified as Type I, and these produce stronger low-level wind anomalies over the tropical southeastern Indian Ocean. The stronger low-level wind anomalies enhance local sea surface temperature (SST) anomalies via positive wind–evaporation–SST (WES) and wind–thermocline–SST (Bjerknes) feedbacks. This corresponds to a strengthening of IOD events due to the increased zonal gradient of SST anomalies over the tropical Indian Ocean. In contrast, Type II models perform poorly in representing the relationship between the SCSSM and JJA IOD or relevant physical processes, corresponding to weakerWES and Bjerknes feedbacks, and produce weaker IOD events. These results demonstrate that the better the model simulation of the critical physical processes, the larger contribution of the SCSSM to the IOD.


Current problems and developments in the theory of the large-scale expansion of the solar corona are reviewed. The outstanding question is whether the energy supply to the quiet corona is mainly thermal conduction outward from a region of active heating at its base or mainly wage propagation outward from the base. It is suggested that the question can be settled only when the properties of the wind can be sampled over a wide range of radial distance from the sun, from far inside the orbit of earth to well beyond. It has been suggested that hydromagnetic waves may drive the expansion of the active corona by direct transfer of momentum as well as energy.


The purpose of this study is to investigate children"s liquid conservation concept according to their ages and task-situations in the water evaporation phenomenon. Thirty from each 4-, 6- and 8-year-old age groups (total of 90 subjects) were selected for this study. The subjects were recruited from two day-care centers, a kindergarten, and an elementary school, in Seoul. Statistical methods used for data analysis were frequencies, percentiles, means, standard deviations and repeated measures ANOVA. As a result, there was a significant difference in children"s liquid conservation concept in the evaporation of water according to their ages and task-situations. 8-year-old children showed levels of cognition than 4- and 6-year-olds. Children showed higher levels of cognition in the task of drying than in the task of water level changes.


REPORT OF A CASE In January 1992, a 64-year-old man with a 1-year history of carcinoma of the colon (Duke's C2) began systemic chemotherapy with fluorouracil, leucovorin, and interferon alfa. His history was also remarkable for multiple actinic keratoses, basal cell carcinomas, and squamous cell carcinomas previously diagnosed and treated. The patient tolerated the first 3 days of treatment without complaint except for fever at the time of interferon alfa administration. On the fourth day, intermittent low- grade fevers and pruritic erythematous scaly papules developed over sun-exposed areas of his face, chest, back, and arms ( Figure 1 and Figure 2 ). The patient successfully completed the full course of chemotherapy. Triamcinolone ointment (0.1%) controlled the cutaneous inflammation and pruritus. The eruption completely cleared 1 week after the end of chemotherapy. A 3-mm punch biopsy specimen was obtained from a representative lesion on the chest ( Figure 3 and Figure 4 ). What is


This paper, the first of two, introduces an observational study of spiral structure in galaxies chosen from the Spitzer Infrared Nearby Galaxies Survey (SINGS). Near-infrared (NIR) and optical data are used to produce mass surface density maps, and from these the morphology of the disc is examined. The aim of this work is to characterize the prevalence of spiral structure in this sample and, in the cases where a clear spiral pattern is found, include the findings in a comparative study (reported in Paper II). A two-armed ('grand design') spiral pattern is found in approximately half of the galaxies studied, including all those that are designated as grand design in the optical, but also including some, but not all, optically flocculent galaxies. It is found that the level of non-axisymmetric structure in the galaxies' mass distributions is only modestly higher in those galaxies that are classified as 'grand design' compared with those that are not, implying that non-grand design galaxies possess significant power in higher order modes. There is no evidence that bars preferentially trigger the spirals, but they do appear to stir up non-axisymmetric structure in the disc. In contrast, there is evidence that strong/close tidal interactions with companion galaxies are associated with strong two-armed spiral structure in the IR, though there are a number of galaxies with relatively weak IR spiral structure that do not possess such companions.


The simplifying original shoreline of vector data into direction-line is the source of picture of baselines of the shape detection. Applying standard algorithms of vector data confining, such as the Douglas-Peucker algorithm, to analyze the real shoreline within direction-line, disregards the specific elements of a guarantee of general marine interests .To solve this problem, this research suggested an improved Douglas-Peucker algorithm. First, determine the curved vertices of the original shoreline as a choice set of points; later filter division points from curved vertices based on corner and length; ultimately, separate the data into different parts in order to complete the Douglas-Peucker algorithm, and compare the threshold of each part to efficiently select specialty points and protect shape detection. This research uses Python language to carry out the algorithm design, and openCV2. The results show that, compared with the Douglas-Peucker algorithm, the improved Douglas-Peucker algorithm improves how detect the contours, and shape detection, and the accuracy of curve simplification also fixed.


Efflux transporters such as ABCB1 (P-gp) and ABCC2 (MRP-2) expressed on the apical membranes of epithelial cells of the intestine represent a formidable barrier for the effective delivery of a plethora of pharmaceutically relevant compounds. Excipients have attracted significant interest in their role as efflux protein inhibitors. To this end, the aim of this study was to examine the biological effects of commonly used excipients, and utilise this information in the design and manufacture of orally disintegrating tablets (ODT) using a design of experiments (DoE) approach. The 'gold standard' model of assessing intestinal efflux modulation remains the Caco-2 Transwell® model. As this method is time and resource consuming, a novel high-throughput screening assay was developed to screen excipients for activity against the ABCB1 and ABCC2 transporters using the specific fluorescent probes rhodamine 123 (R-123) and 5(6)-carboxy-2′,7′-dichlorofluorescein (CDF) respectively. Of all the excipients screened, surfactants showed the highest efficacy against ABCB1 with some materials showing lower IC50 values than the established inhibitors verapamil (VER) and ciclosporin (CsA). One of the lead candidate excipients, poloxamer 407, was incorporated into a high-dose (795 mg) and a low-dose (295 mg) paracetamol (acetaminophen, APAP) formulation at 2 % (w/w). Whilst the development of the high-dose tablets was terminated with a disintegration time of 37 s, conforming to European Pharmacopeia specifications, the low-dose tablets were selected for manufacture using a rotary tablet press. These final formulations had disintegration times of 9-43 s over a range of compressions (6-23 kN), providing tablets that conform to both the European Pharmacopeia and United States Pharmacopeia. Taken with a 250 mL glass of water, these tablets are capable of delivering 5.9 mg of poloxamer 407 to give a final concentration of 2.36 x 10 -3 % (w/v), 2.7 times higher than the determined IC50 value for this excipient. To investigate an additional method of incorporating surfactants into ODTs, granules containing ibuprofen were coated in a Kollicoat IR solution containing 2 % (w/v) PEG 2000, poloxamer 407 or Cremophor EL. The ODTs made from these granules by direct compression produced tablets with disintegration times below 30 seconds, showing the viability of this complementary method of propagating the surfactant content of oral dosage formulations.


Background Providing Psychotherapy, particularly for youth, is a pressing challenge in the health care system. Traditional methods are resource-intensive, and there is a need for objective benchmarks to guide therapeutic interventions. Automated emotion detection from speech, using artificial intelligence, presents an emerging approach to address these challenges. Speech can carry vital information about emotional states, which can be used to improve mental health care services, especially when the person is suffering. Objective This study aims to develop and evaluate automated methods for detecting the intensity of emotions (anger, fear, sadness, and happiness) in audio recordings of patients' speech. We also demonstrate the viability of deploying the models. Our model was validated in a previous publication by Alemu et al with limited voice samples. This follow-up study used significantly more voice samples to validate the previous model. Methods We used audio recordings of patients, specifically children with high adverse childhood experience (ACE) scores; the average ACE score was 5 or higher, at the highest risk for chronic disease and social or emotional problems; only 1 in 6 have a score of 4 or above. The patients' structured voice sample was collected by reading a fixed script. In total, 4 highly trained therapists classified audio segments based on a scoring process of 4 emotions and their intensity levels for each of the 4 different emotions. We experimented with various preprocessing methods, including denoising, voice-activity detection, and diarization. Additionally, we explored various model architectures, including convolutional neural networks (CNNs) and transformers. We trained emotion-specific transformer-based models and a generalized CNN-based model to predict emotion intensities. Results The emotion-specific transformer-based model achieved a test-set precision and recall of 86% and 79%, respectively, for binary emotional intensity classification (high or low). In contrast, the CNN-based model, generalized to predict the intensity of 4 different emotions, achieved test-set precision and recall of 83% for each. Conclusions Automated emotion detection from patients' speech using artificial intelligence models is found to be feasible, leading to a high level of accuracy. The transformer-based model exhibited better performance in emotion-specific detection, while the CNN-based model showed promise in generalized emotion detection. These models can serve as valuable decision-support tools for pediatricians and mental health providers to triage youth to appropriate levels of mental health care services. International Registered Report Identifier (IRRID) RR1-10.2196/51912


Growing industry demands low manufacturing cost, saving of material, low cost material, ease of transportation etc. This demand leads to use different type of material and various techniques to increase productivity. The time factor is very important during loading and unloading of job/pallet. In this research critical parts like Pallet considering machining force taking weight of the work piece into the account. Analysis of pallet is carried out by using finite element package.


Abstract Three augite crystals with differing chemical compositions [Fonualei dacite lava flow, Tonga (Fon39) (En36Fs27Wo37), Alicudi andesitic dike (KC) (En46Fs11Wo43), and Vulcano basalt dike (PD30) (En42Fs12Wo46)] were equilibrated over the temperature range 700-1100 °C through both disordering and ordering reactions ("reversal technique") and then quenched at room temperature. Following each experiment, the partitioning of Fe2+-Mg between M1 and M2 sites of clinopyroxene was determined by single-crystal structure refinement. The Fe2+-Mg partitioning data of the order-disorder reaction, Fe2+M2 + MgM1 = Fe2+M1 + MgM2, in terms of the partition coefficient KD{= [(Fe2+M1)(MgM2)/(Fe2+M2)(MgM1)]}, were then used to calibrate the following geothermometric equations: -lnKD = 2727 (±132)/T(K) - 0.383 (±0.113); (r = 0.99) -lnKD = 4204 (±214)/T(K) - 1.570 (±0.183); (r = 0.98) -lnKD = 5305 (±351)/T(K) - 2.428 (±0.289); (r = 0.98) respectively for Fon39, KC, and PD30. A situation in which thermodynamic parameters depend on crystal composition may be envisaged. It should be noted that such dependence is essentially controlled by the (Ca+Na) and R3+ contents of the clinopyroxene. On the basis of compositional dependence, the following geothermometric equation is proposed: T(K) = [12100 (750) - 27700 (1700)(Ca + Na + R3+) + 20400 (1000)(Ca + Na + R3+)2]/[-lnKD + 7.1 (0.6) - 20.3 (1.4)(Ca + Na + R3+) + 15.2 (0.8)(Ca + Na + R3+)2]


Space-time cluster detection has important applications in public health management and epidemiology to devise disease prevention strategies and to find the causes of a particular disease outbreak in a country. This study introduced a new method to detect the potential space-time clusters with no restriction on cluster shape and size and further visualize them distinctly on the heat map. The proposed algorithm is based on matrix factorization technique to find the significant components in spatial as well as temporal dimension. Applications to malaria data in Khyber Pakhtunkhwa, Pakistan shows that the proposed method is effective in detecting the potential clusters.


The EU has argued that some agricultural subsidies are needed to provide the optimal amount of externalities (both positive and negative) produced by agriculture. The argument is that agriculture is "multifunctional" and externalities such as rural development and landscape would be underproduced, while some forms of pollution (such as nitrogen runoff) would be overproduced without government intervention. Meanwhile, the United States has raised the concern that multifunctionality is primarily an argument to transfer income to producers. In this paper, we discuss the motivation for the EU agri-environmental measures and empirically test for those underlying causes. We find that the programs are not targeted at those regions with the highest environmental need, but neither are they purely a substitute for traditional forms of agricultural subsidies. Demand for general environmental expenditure does influence agri-environmental expenditure as well, as does political structure.


Resting-state functional connectivity is a growing neuroimaging approach that analyses the spatiotemporal structure of spontaneous brain activity, often using low-frequency (<0.08 Hz) hemodynamics. In addition to these fluctuations, there are two other low-frequency hemodynamic oscillations in a nearby spectral region (0.1–0.4 Hz) that have been reported in the brain: vasomotion and Mayer waves. Despite how close in frequency these phenomena exist, there is little research on how vasomotion and Mayer waves are related to or affect resting-state functional connectivity. In this study, we analyze spontaneous hemodynamic fluctuations over the mouse cortex using optical intrinsic signal imaging. We found spontaneous occurrence of oscillatory hemodynamics ∼0.2 Hz consistent with the properties of Mayer waves reported in the literature. Across a group of mice (n = 19), there was a large variability in the magnitude of Mayer waves. However, regardless of the magnitude of Mayer waves, functional connectivity patterns could be recovered from hemodynamic signals when filtered to the lower frequency band, 0.01–0.08 Hz. Our results demonstrate that both Mayer waves and resting-state functional connectivity patterns can co-exist simultaneously, and that they can be separated by applying bandpass filters.


Strongyloides stercoralis is an intestinal nematode with a complex life cycle that involves colonizing and reproducing in the upper small intestinal mucosa. In a healthy host, the parasite usually does not cause any symptoms. We report a gastric infection case of S. stercoralis. A 72-year-old Turkish man was admitted to the Department of General Surgery with complaints of epigastric pain, nausea and vomiting for five days. Upper gastrointestinal endoscopy evidenced a diffuse infiltrate in the stomach, causing decreased distensibility. Microscopically, superficial chronic inflammation with hyperplastic reactive changes and damaged surface was observed. Histopathological examination of the gastric mucosa showed numerous cross-sections of adult worms, eggs and rhabditiform larvae of S. stercoralis developing in the gastric crypts.


Presented is a new clustering algorithm with approximate distributed clustering over a peer-to-peer (P2P) network. The Fisher discriminant ratio is used to dynamically learn the confidence radius based on the data distribution in every local peer. Experimental results show that the proposed approach can achieve better clustering accuracies than the DFEKM algorithm while preserving much lower bandwidth consumptions.


Based on our results, forced diuresis seems to be the method of choice for toxin removal in patients poisoned by A. phalloides; extrarenal removal procedures (such as plasmapheresis) should be considered complementary and are only effective 36 to 48 hours after mushroom consumption. J. PIQUERAS, M D J. R. DURAN-SUAREZ, M D L. MASSUET, M D J. M. HERNANDEZ-SANCHEZ, M D Department of Hematology and Hemotherapy Hospital General " Val1 d'Hebrdn " E-08035 Barcelona Spain


Ruminant Genomics
Ruminants are a diverse group of mammals that includes families containing well-known taxa such as deer, cows, and goats. However, their evolutionary relationships have been contentious, as have the origins of their distinctive digestive systems and headgear, including antlers and horns (see the Perspective by Ker and Yang). To understand the relationships among ruminants, L. Chen et al. sequenced 44 species representing 6 families and performed a phylogenetic analysis. From this analysis, they were able to resolve the phylogeny of many genera and document incomplete lineage sorting among major clades. Interestingly, they found evidence for large population reductions among many taxa starting at approximately 100,000 years ago, coinciding with the migration of humans out of Africa. Examining the bony appendages on the head—the so-called headgear—Wang et al. describe specific evolutionary changes in the ruminants and identify selection on cancer-related genes that may function in antler development in deer. Finally, Lin et al. take a close look at the reindeer genome and identify the genetic basis of adaptations that allow reindeer to survive in the harsh conditions of the Arctic.

Science , this issue p. [eaav6202][1], p. [eaav6335][2], p. [eaav6312][3]; see also p. [1130][4]

 [1]: /lookup/doi/10.1126/science.aav6202
 [2]: /lookup/doi/10.1126/science.aav6335
 [3]: /lookup/doi/10.1126/science.aav6312
 [4]: /lookup/doi/10.1126/science.aax5182


We numerically determine the state of stress in two-dimensional Stranski-Krastanow islands having equilibrium shape. These calculations reveal important generic characteristics and quantitative details of the stress state in equilibrium islands, including stress relaxation and stress concentration. We also use the stresses to determine the first-order energy of introducing dislocations of different Burgers vectors into Stranski-Krastanow islands. These results characterize the ``energy wells'' sought by dislocations to relieve the misfit stress, and suggest that misfit dislocations in islands segregate according to the orientation of their Burgers vector. This segregation allows for more efficient relief of the nonuniform strain in misfitting islands.


Being conductive and flexible, MXenes, including transition metal carbides and nitrides, are expected to compete with, or even outperform graphene as 2D substrates serving in versatile applications. On the other hand, the extraordinary electrochemical activities of MXenes make them promising candidates as electrode materials in rechargeable batteries and supercapacitors, or as electrocatalysts in water splitting. However, MXenes are inclined to self-restack due to hydrogen bonding or van der Waals interactions, which may lead to substantial loss of electroactive area as well as inaccessibility of ions and electrolytes. In this sense, hybridizing 2D MXenes and low-dimensional inorganic nanostructures in elaborately designed architectures is of utmost significance, and provides a chance to integrate their unique properties in a complementary way. As such, this review is dedicated to highlighting recent progress in this regime, putting emphasis on the methods, structural and functional synergies, and energy-related applications. Moreover, the present challenges and the future development directions are also discussed in depth.


The influence of sludge on the groundwater's quality has been shown on the bases of the agricultural exploitation of the sludge from a sewage-treatment plant. Little thickness of unsaturated zone (8.8 m) is not effective protection against the infiltration of the pollution from the surface. Unsaturated zone consist of sand of permeability coefficient k=0,68 m/h. The time of the vertical infiltration into the aquifer has been estimated at t=14,4 days. The investigations carried out during fertilization with the sludge have revealed an undoubted increase in the concentration of some ions as well as the increase in pH of the groundwater. The increase in the amount of some ions (e.g. N-NO3, SO4, Zn) as well as detergents indicates the possibility (as function of time) of reaching higher values than the ones permissible for drinking water. The phenomenon of the increase in the concentration of the particular ions will be accelerated after depletion of sorption of the soil in the unsaturated zone. The time can be estimated for not more than several years, taking into account a small area of the fertilized fields and high contents of "pollution" in the sludge (the total of the heavy metals reaches up to 1,5 g/kg)


Inflammation represents the consequence of capillary dilation with accumulation of fluid (edema) and the immigration of leukocytes. By the end of the last century, Metchnikoff noted the power of certain blood cells to move toward bacteria and foreign substances and ingest them. In fact, leukocytes adhere to the vascular endothelium, and subsequently leave the circulation by transendothelial migration driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to endothelium, basement membranes, and other surfaces on which they crawl is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation can become chronic. The acute process, characterized by neutrophil infiltration and edema, gives way to a subsequent predominance of mononuclear phagocytes or lymphocytes. Insulin-dependent diabetes mellitus is the result of organ-specific autoimmune destruction of the insulin secreting beta-cells in the pancreatic islets of Langerhans. It has become evident that diabetes mellitus is a multifactorial disease caused in part by infiltrating T-lymphocytes, comparable to situations of inflammation. After presentation of the different effectors of the immune system and their fluxes through the body, this review will propose a general model of adhesion between leukocytes and endothelial cells. It will emphasize how the homing specificity of lymphocyte subsets to different lymphoid organs is ensured, and how leukocyte migration to sites of inflammation is regulated. Finally, general therapeutic perspectives based on adhesion molecules leading to cure or prevention of chronic inflammation will be discussed.


A unique, platinum-catalyzed, direct C-H acylation of 2-(aryloxy)pyridines with acyl chlorides is discovered. The reaction requires neither an oxidant nor other additives. When both ortho positions of the aryl group are accessible, the double acylation occurs readily to produce the diacylated products. Aliphatic, aromatic, and α,β-unsaturated acyl groups can all be introduced. The acylation reaction may proceed through an analogous aromatic electrophilic substitution triggered by the nucleophilic attack of the platinum at the acyl chloride.


Two versions of a capture theory that both satisfy Coulomb boundary conditions but differ in short-range distorting potential are compared. Rigorously calculated differential and total cross sections in first- and second-order perturbation theory are discussed for p+H collisions at projectile energies of 125, 1000 and 5000 keV. It turns out that the inclusion of second-order contributions leads to a satisfactory agreement with the experimental angular distributions.


I. INTRODUCTION The purpose of this paper is primarily to present a "state of the art" survey of the role played by static electricity in the textile and fiber industries. The current situation, including the problems and suggested solutions, both successful and unsuccessful, will be reviewed. Finally, useful applications of electrostatics in the industry will be described.


We investigated the causal effect of college education on smoking, drinking, sleeping, and cancer screening behavior in Japan. To estimate said effect, we leveraged a unique instrument in which a mismatch between Japanese superstition and school year in 1967 leading to an increase in college attainment. We found that a longer year of college education was associated with reductions in smoking and drinking and improvements in sleeping and the use of cancer screening. We also explored heterogeneity across genders and found that women drive the causal relationship between college education and health behavior in Japan.


During videolaparoscopic operations on bile eliminating pathways when the patent cystic duct is catheterized for cholangiography or drainage of choledochus by the Halsted-Pikovsky method there appear problems with the introduction of the tube into the cystic duct. In order to facilitate the cystic duct catheterization the authors propose to use a fishing-line conductor with the diameter of 0.8-1.0 mm. The method is simple, accessible, facilitates and accelerates the catheterization of the cystic duct and prevents compression of the tube lumen when fixing it with the endoclamp.


This paper presents an experimental determination of energy requirement for greenhouse heating. The overall heat loss coefficient, heat input, the control factor for air‐tightness, the rate of heat loss and the thermal screen effectiveness were calculated. The relationships between the overall heat loss coefficient and the wind speed, and the outside temperature were modelled, including the measured and calculated values. It was found that the thermal screen effectiveness was 16 and 19.8% for the polyethylene (PE) and polyester screens, respectively. Copyright © 2005 John Wiley & Sons, Ltd.


Our current understanding of the core-collapse supernova (CCSN) explosion mechanism is incomplete, with multiple viable models for how the initial shock wave might be energized enough to lead to a successful explosion. Detection of a gravitational wave (GW) signal emitted in the initial few seconds after stellar corecollapse would provide unique and crucial insight into this process. With the Advanced LIGO and Advanced Virgo detectors expected to soon approach their design sensitivity, we could potentially detect this GW emission from a supernova within our galaxy. In anticipation of such a scenario, we study how well the BayesWave algorithm can recover the GW signal from CCSN models in simulated advanced detector noise, and optimize its ability to accurately reconstruct the signal waveforms. We find that BayesWave can confidently reconstruct the signal from a range of supernova explosion models in Advanced LIGO-Virgo for network signal-to-noise ratios & 30, reaching maximum reconstruction accuracies of ∼ 90% at SNR ∼ 100. For low SNR signals that are not confidently recovered, our optimization efforts result in gains in reconstruction accuracy of up to 20-40%, with typical gains of ∼ 10%.


The present work deals with a project aiming to increase the value of photovoltaic (PV) solar production for applications in residential building. To investigate this issue, this paper focuses on the optimal operation of a PV-based multi-source system and energy management. It is composed of two principal mechanisms of control: anticipation and reactive management. The anticipation, based on forecast information concerning load, electric prices, and meteorological conditions calculates an optimum planning for the allocation of the sources and the load rescheduling to satisfy the demand of user and also to minimize the energy cost. The reactive management procedure aims to realize the calculated plan and to take the appropriate correcting actions to handle possible unpredicted disturbances. The problems are formulated by using the Mix Integer Linear Programming (MILP) algorithm, considering various constraints. An example is given to illustrate the solution approach.


ABSTRACT Cells of Escherichia coli undergo a metabolic switch associated with the production and utilization of acetate. During exponential growth on tryptone broth, these cells excrete acetate via the phosphotransacetylase-acetate kinase (Pta-AckA) pathway. As they begin the transition to stationary phase, they instead resorb acetate, activate it to acetyl coenzyme A (acetyl-CoA) by means of the enzyme acetyl-CoA synthetase (Acs) and utilize it to generate energy and biosynthetic components via the tricarboxylic acid cycle and the glyoxylate shunt, respectively. This metabolic switch depends upon the induction of Acs. As part of our effort to dissect the mechanism(s) underlying induction and to identify the signal(s) that triggers that induction, we sought the sigma factor most responsible foracs expression. Using isogenic strains that carry a temperature sensitivity allele of the gene that encodes ς70 and either a wild-type or null allele of the gene that encodes ςS, we determined by immunoblotting, reverse transcriptase PCR, and acs::lacZtranscriptional fusion analyses that ς70 is the sigma factor primarily responsible for the acs transcription that cells induce during mid-exponential phase. In contrast, ςS partially inhibits that transcription as cells enter stationary phase.


Engineering behavior of fine-grained soils is mainly influenced by its fabric structure, which is the arrangement of soil particles and distribution of the pores. For determination of soil fabric, earlier researchers have relied on instrumentation techniques such as scanning electron microscope (SEM) and mercury intrusion porosimetry (MIP). However, due to small sample size, complexities involved with the sample preparation, and destructive nature of these techniques, precise interpretation of the results becomes a challenging task. In order to overcome this, efforts were made by the authors to explore the potential of impedance spectroscopy, which is a non-destructive and non-invasive technique of characterizing the soil mass, for determining its fabric. Details of the methodology adopted to achieve this are presented in this paper, which also elaborates the setup employed to determine the electrical conductivity of the marine clay samples in their undisturbed and remolded states. Further, the observed directional dependency of electrical conductivity, i.e., electrical anisotropy, has been expressed as the anisotropy coefficient, Ae, and its potential in defining the fabric anisotropy has been demonstrated. The results have been critically examined vis-a-vis the observations from the SEM and MIP studies. The study reveals that the higher the deviation of Ae from unity, the higher would the fabric anisotropy be, which is indicative of the fabric of the fine-grained soils.


This book presents the main findings of a research report that was conducted in November 2012. It addressed the impacts of the Austerity Measures on the livelihoods of the citizens of Jonglei State in the Republic of South Sudan. It gives explanations on critical economic measures that were taken by the Government of South Sudan in response to it decision of shutting down the oil production of which the pipeline was based in Port Sudan- Khartoum. The thought for the government in doing this was to counterbalance it fragile economy which is 98% depending on the oil. This led to the reduction of the salaries, allowances and incentives of the civil servants in the country. The government of South Sudan accused Sudan of stealing it oil, thus leading to the shutdown of the oil. This was seen when clashes broke out along the disputed areas of Abyiei and Heglig. Though the International community later intervened in a timely manner. Furthermore, this research cautioned that, before taking Austerity Measures, socio-economical research should have been conducted by the government in order to acquaint with the effect of its implementation on public servants, and the citizens of South Sudan


CD8 T-cell responses are critical for protection against intracellular pathogens and tumors. The induction and properties of these responses are governed by a series of integrated processes that rely heavily on cell–cell interactions. Intercellular adhesion molecule (ICAM)-1 functions to enhance the strength of antigenic stimulation, extend the duration of contact with antigen-presenting cells, and augment cytokine signals, which are all factors that influence peripheral CD8 T-cell differentiation. Although previous studies suggest that ICAM-1 is essential for establishing memory T-cell populations following peptide immunization, the roles of ICAM-1 in antiviral cellular immunity are less well understood. Here we show that, following a prototypic acute viral infection, the formation and maintenance of memory-phenotype CD127hi, KLRG-1lo CD8 T cells does not require ICAM-1. Nevertheless, ICAM-1 expression on nonlymphocytes dictates the phenotypic and functional attributes of the antiviral CD8 T-cell populations that develop and promotes the gradual attrition of residual effector-like CD127lo, KLRG-1hi CD8 T cells during the memory phase of the response. Although memory T cells do emerge and are maintained if ICAM-1 expression is abolished, the secondary proliferative capacity of these T cells is severely curtailed. Collectively, these studies reveal potential dual roles for ICAM-1 in both promoting the decay of effector responses and programming the sensitivity of memory CD8 T cells to secondary stimuli.


A new stroboelectric tuner for musical instruments is claimed to be simpler to construct and to use than devices so far described. A single strobo disk rotates at a very constant speed. It is marked out in 12 concentric tracks, each representing a semitone of the musical scale. Each track is divided up into a number of equal divisions such that the ratios of the number of divisions from track to track are almost equal to the ratios of frequencies of successive semitones of the equal tempered scale. The rotating disk is illuminated by a pulse-fed neon lamp. The incoming sound wave is amplified, passes through a zero crossing detector, is then differentiated; the resulting pulses are amplified and fed the neon lamps via a step-up transformer. The lamp thus emits short-duration flashes at the fundamental frequency of the incoming sound wave. When this frequency is any submultiple of one of the track frequencies, the divisions in that track appear stationary. Due to the pulsed illumination these divisions appear perfectly crisp at all frequencies. Sharp or flat misintonation causes the divisions to appear to move clockwise or anticlockwise. No switching or other manual action is required when moving from semitone to semitone, nor from octave to octave. A maximum error of less than 1 cent can be achieved.


Innovative course design in higher education:
Applying service-dominant logic to an operations management course

Abstract

Purpose
Since the ground-breaking article "Evolving to a New Dominant Logic for Marketing" (Vargo & Lusch, 2004), the service-dominant logic (S-D logic) has received a great deal of attention in particular within marketing, arguing that service is the basis of economic exchange, instead of a focus on goods as outputs. Living in a service and knowledge intense society, the trend towards a focus on services also includes industries formerly focused on products. The trend of servitization, referring to a transition towards an increased focus on services in the overall offering (Vandermerwe & Rada, 1988; Baines & Lightfoot, 2013), affects the way business are made and the operations within the organisation. The S-D logic is argued to correspond well to this service-intense society (Ford & Bowen, 2008), and offers a way to understand value creation where S-D logic argues that service is the process of actually using competences to create benefit for some actor (Vargo & Lusch, 2004).
Aligned with this trend in society, we can see development within higher education, e.g. the raise of MOOCs (Sultan, 2014). To respond to societal development, higher education need to adress new requirements and changing expectations from students while providing increased value for students.
However, research on S-D logic in higher education is scarce (Kryvinska et al., 2013) and the existing contributions focus on the importance to include S-D logic as a subject into business school courses (e.g. Ford and Bowen, 2008), for example courses in operations management (OM). To our knowledge there are no publications that applies the S-D logic to the design of education rather than to include the subject.
This paper aims to bridge this gap by proposing an S-D logic adapted analytical tool for education activities.
The analytical tool combines a knowledge dissemination (KD) framework by Paulin (2013) with the foundational premises of S-D logic as described by Vargo and Lusch (2004, 2008). The KD framework consists of five components, or groups of factors influencing how knowledge is disseminated. These components are Actors (including sources and recipients), Media, Content, Context, and Activity. The premises of S-D logic (or the axioms) include "service is the fundamental basis of exchange", "the customer is always co-creator of value", "all economic and social actors are resource integrators" and "value is always uniquely and phenomenologically determined by the beneficiary" (Lusch and Vargo, 2014; 15-16).

Design/methodology/approach
In this paper we use the activities in one OM course given at Chalmers University of Technology to exemplify how the proposed analytical tool can be applied. The course was selected since it is perceived as a traditionally designed course regarding content and teaching activities.
In order to understand formal prerequisites for course design documents covering formal requirements, including Standards and Guidelines for Quality Assurance in the European Higher Education Area (ESG), the Swedish Higher Education Ordinance and programme syllabi, were analysed.
Information regarding the particular course design was collected via two semi-structured interviews with the course examiner and one additional teacher and by studying official course documentation including syllabus, lecture material, and examination documents. Triangulation of data was obtained by including the student perspective via analysis of course evaluations plus one group interview with five previous students.

Findings
We have found that when the proposed tool is used to analyse course activities, it highlights potential development areas to better align education activities with S-D logic.
We have also found that certain teaching activities such as lectures are limited in their alignment with the S-D logic, while other activities such as experiential learning projects correspond well with the S-D logic. The primary media used in most activities analysed is face-to-face communication which enables alignment with axioms 1 to 3. We have indications based on the examiners' underlying pedagogical philosophy that the axioms of S-D logic was not consciously followed when the course was originally designed.

Relevance/contribution
This paper applies S-D logic to a new setting; design of higher education. One contribution from this paper is to advance the understanding of knowledge dissemination in higher education, through the proposed analytical tool combined of service-dominant logic axioms and a knowledge dissemination framework. Further, the findings offer opportunities for development of higher education activities by, for example, novel and additional approaches to knowledge co-creation and resource integration compared to traditional activities.


Water vapor mixing ratios in the upper troposphere and lower stratosphere measured by the Aura Microwave Limb Sounder (MLS) version 2.2 instrument have been compared with Global Forecast System (GFS) analyses at five levels within the 300‐100-hPa layer and North American Mesoscale (NAM) model analyses at six levels within the 300‐50-hPa layer over the two years of 2005 and 2006 at four analysis times (e.g., 0000, 0600, 1200, and 1800 UTC). Probability density functions of the vapor mixing ratios suggest that both analyses are often moister than Aura MLS values, but NAM model analyses agree somewhat better with Aura MLS measurements than GFS model analyses over the same North American domain at the five common levels. Examining five subsets of the global GFS domain, the GFS model analysis is moister than Aura MLS estimates everywhere but at 150 and 100 hPa in all regions outside of the tropics. NAM model analysis water vapor mixing ratios exceeded the Aura MLS values at all levels from 250 to 150 hPa in all four seasons of both years and some seasons at 100 and 50 hPa. Moist biases in winter and spring of both years were similar at all levels, but these moist biases in summer and fall were smaller in 2005 than in 2006 at all levels. These differences may be due to the change in the NAM from using the Eta Model to using the Weather Research and Forecasting model (WRF) in June 2006.


Emollient preparations play a central role in the treatment of people with dry skin associated with conditions such as atopic eczema.1,2 As well as being advised to apply emollient creams or ointments directly to the skin, people with atopic eczema are commonly prescribed bath emollients.3 Each year, the NHS spends over £16million on bath emollients (at an average cost of £6.29 per item).4 This represents 38% of the total cost of treatments prescribed for preschool children with eczema, matching the proportion spent on emollients for application directly to the skin.5 What clinical contribution do bath emollients make in the treatment of people with atopic eczema?


Two different methods for the numerical simulation of steady, invisced, nonequilibrium reactive flow governed by Euler equations augmented by a 5-species 17-reaction finite-rate dissociation model are studied. The employed approximations are based on a conservative mixed finite-volume/finite- -element upwind formulation. The study concentrates on the efficiency of the pseudo-time integration methods as iterative algorithms. The iterative properties of the basic method are demonstrated by various computations of flow fields arount blunt bodies. In particular, the effect of varying the global Damkholer number (i.e. the size of the geometry ) is illustrated. A variant of the basic method is proposed. We know that for steady (external) flows with uniform free-stream, the total enthalpy is constant throughout the domain. Hence, an algorithm which conserves this quantity has been implemented in which the energy equation ( in differential form ) is not solved but replaced by its (algebraic) first integral. The extension of existing flux-vector splittings (FVS) to this context where one less PDE is solved and one algebraic constraint is enforced, is examined in Section 4 in which the FVS is demonstrated to be proper. Finally, the efficiency of the proposed new approach is assessed by numerical experiments for first and second order approximation schemes.


Background: Goldsmiths are known for using potent toxic chemicals which pose a health risk to workers which occur either by inhalation or by dermal contact. Chemicals taken up by the body causes damage to vital organs of body such as kidneys, lungs etc., there by affecting their normal physiology and function.   Objective: Present study reports the assessment of Nephrotoxicity among goldsmiths who are employed from 4 years-50years in jewellery making units.  Methods: The study involved various environmental parameters such as determination of TSPM for air pollutant analysis, biological parameters such as urinary β-2-microglobulin, urinary Creatinine, urinary albumin, urinary total protein concentrations, and serum concentrations of Glutathione-S-Transferase, Catalase, extracellular Super Oxide Dismutase and total protein in both control and test samples. Result: Environmental, biological parameters of exposure and renal dysfunction were examined in a group of goldsmith workers (n=22) and in an un-exposed control group (n=22).The parameters examined were compared between the two groups and related to different exposure parameters. The TSPM concentrations ranged between 75-664 µg/m3. The concentrations of β-2-microglobulin were 0.14-1.2 mg/g of Creatinine, In exposed group Serum concentration of Glutathione-S-Transferase was 1.19 ± 0.48, Catalase 5.1 ± 0.61, extracellular Super Oxide Dismutase 281.2 ± 90.8, and total protein 5.9 ±0.83. However there were no significant changes in the urinary albumin and urinary total protein concentrations between the exposed and the control population.


We interviewed six people who led teams that created web sites ena- bling Hurricane Katrina survivors to report their status. We learned that inter- viewees did not discover and communicate with other teams when they started their projects, which resulted in redundant sites. The absence of a shared task impeded trust between teams, ultimately inhibiting data collection and aggrega- tion. Moreover, communication within teams was problematic; developers who had adequate technical skills to work alone were more positive about their sites' success compared to developers who had to shore up skill weaknesses through collaboration. These problems did not simply result from team leaders' over-sized egos, since site creators were generally motivated by concern for other people instead of self-interested motivations. Rather, these problems highlight the need for improved development methods and systems to help de- velopers discover and communicate with other teams' leaders in order to col- laborate on widely distributed, time-critical projects.


Waste water is disposed to sewage disposal plant by underground PE double wall pipes. Various processes have been introduced to join PE pipes, but most of these methods have many disadvantages such as costs, lack of reliability and difficulties in joining, etc. Recently butt welding has been paid much attention to joint PE pipes as this process has many advantages such as cost, safety and reliability. In this study, newly developed heat plate, a patent-pending heat plate with a groove, was used to butt-weld PE double wall pipes with different misalignment gaps to simulate real underground conditions, and the butt welding temperature of PE pipe was determined by thermal analysis (Thermal Gravimetric Analysis, Differential Scanning Calorimetry and Dynamic Mechanical Analysis). The resulting joining characteristics of double wall pipes were compared with those from a conventional heat plate, in terms of stiffness, flattening and leakage tests. The results from the stiffness and flattening test showed that there were no big differences between the butt-welded joints made from these two plates. From the leakage test, although PE pipes welded with a conventional heat plate did leak below the required test conditions (10 min. at 0.75kgf/cm2), the pipes welded with a patent-pending grooved heat plate did not show any leakage even at a pressure 1.5 times higher than the required conditions. It was noted that by utilizing a grooved heat plate more complete fusion at the pipe joints could be obtained, which in turn induced a high quality joints.


I OFFER THIS ESSAY AS A CONTRIBUTION TO A DISCERNIBLE MOVEMENT in Shakespeare studies which is once again raising the question of the relation of the plays to early modern religious discourse. For a long time this relationship was addressed in the context of biographical criticism, with the texts being read as cryptic testimonials to Shakespeare's Catholicism, his royalist Anglicanism, his agnosticism, his hostility to Puritanism, and so on. In the new assessment of Shakespeare's work and religion, biographical concerns have been displaced by a focus on the texts as part of a broad cultural order and on the great variety of contemporary discourses that nourish the plays and the dramatic conflicts they represent. The interpretive process is complicated by the issue of censorship, a force difficult to assess but undeniable, and, in the case of Hamlet, by the existence of three different texts with their vast number of variants. Religious discourse is integral to Hamlet, but Shakespeare's representation of religion in the play is oblique and inconsistent, and critics have come to many different conclusions about Hamlet's religious content. The play's inconsistent representation of religion is interesting in itself, and I would argue that to a certain extent the forces producing this instability and the role of religion in the play's ideological drama are accessible to historicist criticism. We can, for example, illuminate the representation of religion in the play by viewing it in relation to Hamlet's subjectivity, which is a principal site of ideological contention. We can also engage with specific religious discourses in the text, among them Roman Catholicism, neo-Stoicism, and Protestantism, and with Shakespeare's representation of their historical and institutional affiliations. To classify Stoicism as a religious discourse is arguable, but it clearly functions as an important constituent in the contemporary synthesis of humanism and Christianity. Considering Stoicism within a religious context illuminates Hamlet's involvement with comprehensive ideological systems and helps to prepare the way for an analysis of his subjective transformation at the end of the play. The language and theology of Roman Catholicism emerge most clearly in Hamlet in the prince's encounter with his father's spirit, where the Christian and specifically purgatorial context that Shakespeare creates for the Ghost is rather surprising. The play contrasts sharply in this respect with The Spanish Tragedy, where the ghost of Don Andrea inhabits a classical underworld derived from the sixth book of Virgil's Aeneid, a strategy that allows Kyd to avoid the ideological pitfalls of representing a Christian afterlife. The spirit of old Hamlet explicitly identifies his situation beyond the grave, speaking of the "sulph'rous and tormenting flames" to which he must render himself, and of the "certain term" of penance he must endure until "the foul crimes done in my days of nature / Are burnt and purged away"


Given a finite totally ordered set of linguistic terms, the operations intersection and connected union provide a lattice structure to the set of hesitant fuzzy linguistic term sets. In this framework, hesitant fuzzy linguistic descriptions of a given set of alternatives are considered. A distance between hesitant fuzzy linguistic descriptions is introduced based on the properties of the lattice. This metric structure allows distances between decision makers to be computed. A centroid or group representative is defined in group decision-making processes where decision makers are assessing different alternatives by means of hesitant fuzzy linguistic term sets.


Malaysia has undergone a transformation over the past few decades as they move from a primarily agrarian society to modern industrial society. These economic changes have important implications on demographic and labour issues. Even though an increase in demand for a highly skilled workforce has seen more women enter the labor force, but the number of women at top management level is considerably very low. "Glass ceiling" in this study represents the barriers that women face to enter top management positions in the organization. Glass ceiling is categorized into two main categories in this study: (1) personal challenges that consist of demographic factors, family commitment and family support; and (2) work challenges that consist of negative stereotype, workplace arrangement, organizational culture and career development opportunities. The implications of this issue range from micro level, such as women's dissatisfaction over the job opportunities and exiting from the labor force to macro issues such as brain drain and migration. This study aims to identify the main challenges that women face to enter top management positions in Malaysia either it is from personal challenges or work challenges. 300 respondents were selected in order to collect the data. Using cross-tabulation analysis and descriptive analysis, it was found that demographic factors, family commitment, organizational culture and career advancement opportunities have a more significant influence on women's intention to enter top management. While family support, negative stereotype and workplace arrangements have less significant influence on women's intentions to move up the career ladder. From the findings of this study, it can be concluded that the "glass ceiling" phenomenon that hinder women's intention to enter top management in Malaysia come from both personal and employers' challenges.


Summary The fraction of human serum precipitated by 45% saturated ammonium sulphate has been submitted to immunochemical analysis. "Fraction 45" was separated by ammonium sulfate in the presence of phosphate buffer into seven main subfractions. A number of immune serums were prepared against a part of these subfractions and against other fractions of human serum. The reactions in gelled media (simple diffusion in tubes) of these immune serums with Fraction 45, its subfractions (brought to the same nitrogen concentration), and other fractions, were carried out and analyzed. The identification of the precipitation zones of sufficient density and penetration given by the same antigen in these multiple reactions was mainly carried out by a procedure previously described which involves only the comparison of the tubes. Fifteen distinct antigens and a family of at least three antigens with similar properties of solubility and immunogenic power, making a total of 18 antigens could be distinguished. It was demonstrated that the 18 antigens found in Fraction 45 were different from the seven antigens already described in the fraction soluble in 65% saturated ammonium sulfate. Consequently, the number of antigenic components of human serum that we have described to date is not less than 25—the components of certain fractions remaining to be described. Unispecific immune serums against six major components of Fraction 45 and two major components of other fractions were prepared.


"Not-specified interstitial" lesions represented mostly cryptogenic fibrous alveolitis, extrinsic allergic bronchioloalveolitis prevailed among "disseminated" lesions, "infiltrative" lesions were proved to be extrinsic alveolitis or disseminated carcinoma. Among more definitely formulated suppositions of the clinician, cryptogenic alveolitis was proved in more then 50% of cases often modified by extensive fibrosis, organized pneumonia, cholesterol pneumonia or minute desquamative pattern. A similar relation of diagnostic correctness was found in allergic bronchioloalveolitis suprisingly often modified again by fibrosis and cholesterol pneumonia. Valid diagnoses were found in sarcoidosis, presumed Goodpasture syndrome harboured only pneumoconiotic stigmatization. In brief: Bioptical diagnosis nearly always replaced a vague clinical evaluation whereas definite nosological formulations were proved, turned more exact or changed in equal proportions, biopsy was not found contributory but in two cases.


This chapter deals with the 'other causes of parkinsonism with the exclusion of idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration. It is a cursory glance over the endless list of 'secondary' causes of parkinsonism or parkinsonism due to acquired and inherited metabolic and neurodegenerative diseases. With the exception of drug-induced parkinsonism and 'vascular' parkinsonism, most such cases are rare. However, single rare causes must not be overlooked as there can be specific therapeutic consequences. Parkinsonism is often present amid a constellation of other symptoms. Careful evaluation of the personal, familial and environmental context, mode of onset and progression, clinical features, and drug response, together with imaging, biochemical and molecular tests, help in determining the underlying disease.


Using NMR inversion recovery experiments and XPLOR distance restraint calculations, we recently deduced the structure of ferriprotoporphyrin IX (FPIX) heme mu oxo dimer-antimalarial drug complexes for chloroquine (CQ), quinine (QN), and quinidine (QD) at atomic resolution [A. Leed et al., Biochemistry 2002, 41, 10245-55]. Using similar methods, we now report an unexpected structure for the complex formed between FPIX and the related drug amodiaquine (AQ). The deduced structure is further supported by comparing AQ chemical-shift data to restricted Hartree-Fock calculations. The structure further highlights the critical nature of quinoline drug side-chain composition in stabilizing noncovalent association to FPIX. Heme Fe-AQ proton distances are longer, relative to those of the CQ complex, and the AQ aromatic side chain seems to have a significant role in stabilizing the complex. Relative to the FPIX-CQ complex, a similar 2:1 stoichiometry was determined for the AQ complex, in contrast to a 4:1 stoichiometry previously suggested from calorimetry data. These solution structures add to our rapidly growing understanding of the mechanism of quinoline antimalarial drug action and will help elucidate the mechanism(s) of quinoline antimalarial drug resistance phenomena.


The overall goal of this chapter is to give the reader insights into the human factors issues related to the use of tactile displays. Torso-mounted displays, which are particularly suited for direction and orientation cues, are emphasized. First, perceptual issues relevant to tactile stimulation are discussed. These include issues regarding spatial acuity and absolute localization of tactile cues on the torso, such as internal reference points, anchor points, and spatial accuracy. In addition, tactile illusions, burst durations, and temporal effects are discussed in relation to tactile torso display design. A second section focuses on issues related to coding principles; that is, how best to develop tactile patterns to be intuitively understood within a specific operational context. Cognitive issues are then addressed, such as how tactile stimulation can either alleviate or exacerbate attention tunneling, and the extent to which multiple tactile patterns can be used effectively. Cognitive processes related to tactile cueing are described, followed by issues related to multisensory integration and multifunction displays. Finally, issues related to user acceptance are discussed.


Hypothesis To characterize transcanal endoscopic landmarks of the medial labyrinthine wall and correlate these with anatomical features of the fundus of the internal auditory canal (IAC). Background The transcanal transpromontorial approach (TTA) enables minimally invasive access to the IAC. The establishment of a landmark-based dissection technique for the approach is crucial to avoid injury to the facial nerve. Methods Twenty temporal bones were dissected endoscopically through the TTA. Furthermore, high-resolution computed tomography (CT) scans from ten adult normal temporal bones were analyzed and three-dimensionally reconstructed. Results A stepwise dissection technique for the TTA was demonstrated depending on a newly described landmark used in the identification of the facial nerve. The proposed landmark, which was named the intervestibulocochlear crest (IVCC), is an integrated part of the otic capsule. It can be differentiated after the excision of the lateral labyrinthine wall as a laterally based bony pyramid between the cochlea and the vestibule. Its medially directed apex blends with the central part of the falcifrom crest and points to the distal part of the meatal facial nerve. The IVCC is best detected on axial CT images at the level of the tympanic facial nerve. The union between the IVCC and the falciform crest appears radiologically as a short stem or mini-martini glass. Conclusion The proposed IVCC is a novel landmark with a consistent relationship to the IAC fundus and the facial nerve. It may be utilized in conjunction with the falciform crest to identify the facial nerve during minimally invasive transcanal surgeries.


Two growth experiments were conducted to estimate the minimal dietary vitamin A requirement for juvenile grass shrimp, Penaeus monodon. In expt. 1, purified diets containing 0, 1,500, 3,000, 15, 000, 30,000, 45,000 and 60,000 retinol equivalent (RE)/kg (i.e., 0, 5,000, 10,000, 50,000, 100,000, 150,000, 200,000 IU/kg) of supplemental vitamin A (retinyl acetate) were fed to P. monodon (mean initial weight 0.97 +/- 0.01 g) for 8 wk. In expt. 2, diets with 0, 600, 1,200, 1,800, 2,400, 3,000, 3,600, and 4,500 RE/kg (i.e. , 0, 2,000, 4,000, 6,000, 8,000, 10,000, 12,000, 15,000 IU/kg) of supplemental vitamin A were fed to the shrimp (mean weight 0.68 +/- 0.01 g) for 6 wk. The basal unsupplemented diet contained 54 RE vitamin A/kg, and supplemental levels were confirmed by analysis. Each diet was fed to three replicate groups of shrimp. In expt. 1, shrimp fed diets supplemented with 300 RE vitamin A/kg had significantly greater weight gain (P < 0.05) than those fed the unsupplemented control diet and diets supplemented with >===" BORDER="0">30,000 RE vitamin A/kg. Survival rate was higher in shrimp fed diets supplemented with 1,500-30,000 RE vitamin A/kg than shrimp fed the control diet. Highest blood triglyceride concentration and body lipid concentration were in shrimp fed diets supplemented with 45,000 and 60,000 RE vitamin A/kg, respectively. Eye vitamin A concentration and hepatopancreatic total lipid concentration in shrimp generally increased as dietary vitamin A supplementation increased. In expt. 2, feed efficiency was highest in shrimp fed diets supplemented with 2,400, 3,000, 3,600 and 4,500 RE vitamin A/kg, followed by shrimp fed diets with 600 and 1,200 RE vitamin A/kg and finally the unsupplemented control group. Shrimp fed diets supplemented with vitamin A had significantly higher survival percentages than those fed the unsupplemented control diet. Weight gain percentage of the shrimp analyzed by broken-line regression indicated that the minimal dietary vitamin A concentration in growing P. monodon is 2,511 RE/kg ( approximately 8, 400 IU/kg).


Saltcedar (Tamarisk spp.) is a non-native facultative phreatophyte that has infested riparian floodplains, fallow farmlands, reservoir deltas and ephemeral washes throughout the southwestern United States. Land and water managers throughout the region are implementing aggressive programs to eradicate this tree in hopes of achieving water savings and restoring native vegetation communities and wildlife habitat. In 1941, Saltcedar began aggressively colonizing the I 00-year floodplain along the middle Rio Grande on the Pueblo of Santa Ana ("the Pueblo") in central New Mexico. Dense thickets formed in areas previously occupied by salt tolerant grass and riparian shrub communities. Soil assessments were conducted in 1999 on a 115-acre site to evaluate the potential for re-establishing native plant communities to the site. A soil survey was performed by evaluating soil profiles along transects systematically established throughout the study site. Textural class, pH, saturation percent, calcium, magnesium, sodium, sodium adsorption ratio (SAR) and soil apparent electrical conductivity (EC) were determined. Analyses revealed highly variable SAR values ranging between 4.1 and 78.9, with the higher values associated primarily with fine textured soils. Saltcedar was mechanically removed from the 115-acre field in winter 1999, followed by "deep-ripping" clay layers with a slip plow. Gypsum was applied to the soils at rates ranging between 10-30 t ,c-,, depending upon SAR values. A permanent sprinkler irrigation system was installed in March 2000 on 65-acres that was seeded with seven native grasses and a sterile cover crop, (Triticum elongatus). The 65-acre field was irrigated daily from June 15 September 30, 2000, for salt leaching purposes. Three vegetation plots were established in each of the I 0, 20 and 30 t eo-i gypsum zones (9 plots total) in September 2000 and were analyzed for species establishment and relative cover. This case study has demonstrated that soil reclamation for revegetation of native grasses is possible using techniques developed in agriculture. However, our study also confirms that reclamation of sodic and saline soils is an expensive undertaking. Additional


This paper introduces a novel adaptive continuous beam steering (ACBS) solution for quasi-optical antenna technologies. The main advantages of this solution compared to discontinuous beam switching approaches are small steering angle steps (high resolution), improved beam crossing level and lower RF losses. This solution is based on a phase correcting aperture transfer function and the relation between a focal array amplitude tapering and its phase center displacement. The proposed solution is verified by comparing its calculated results with 3D full-wave simulations. Using a 2×2 focal source array illuminating a Fresnel dielectric lens, it is possible to achieve a scanning range of 1.6° with a steering angle step of 0.3° and a beam crossing level of 0.2 dB. The ACBS solution can be integrated into active antennas for self-alignment purposes.


The concept of a cognitive radio assumes that the receiver is able to determine the activity level across a large range of spectrum in order to assign a channel for its use. Hence a key function is a spectrum monitor to detect the spectrum availability as a first step. This thesis explores the requirements and design issues for the spectrum monitor receiver. The main challenge of this receiver design is to draw a spectrum map covering a wide range of frequency that is fast and accurate enough while consuming low power compared with the main transceiver circuits. The history and applications of the concept of cognitive radio (CR) are overviewed, followed by a wideband receiver architecture review, giving a wide range of scheme options for the proposed spectrum monitor. The concept of figure of merit (FoM) is then introduced. This concept helps to predict the performances versus power consumptions for active components over the next few years. By exploring the trend and relationship among FoMs, performances and time scales, a design approach is obtained to be used as a guide for system level receiver budget design. Then the spectrum monitor architecture is explored depending on the application and the figures of merits. For a representative cognitive radio application it is shown that the dual-down conversion architecture is suitable for the spectrum monitor, and the system specifications are given. Using these system specifications, the circuit level design of two of the key blocks is explored, where the requirements are significantly different from conventional designs reported in literature. A wide tuning range ring oscillator based PLL that is suitable for the frequency conversion and tuning functions is designed, fabricated and tested. A design method for high frequency on-chip bandpass filters is presented and experimentally tested. Comments on this research and future works are finally discussed.


This article presents an in-depth analysis of the Private Finance Initiative (PFI) procurement system for the construction of major highway works in the United Kingdom under the principles of design, build, finance, and operate (DBFO). This purpose of the article is to determine whether PFI/DBFO is a successful procurement route in providing value for Money (VfM) for the development of major highway works. Thereafter, by careful analysis of the results of the research, the future of major highways work under PFI/DBFO forms of procurement can be predicted along with any relevant recommendations for further research, in order to improve the performance of PFI/DBFO VfM systems.


Background:Consumer assessment of health care is an important metric for evaluating quality of care. These assessments can help purchasers, health plans, and providers deliver care that fits patients' needs. Objective:To examine differences in reports and ratings of care delivered to adults and children and whether they vary by site. Research Design:This observational study compares adult and child experiences with care at a large west coast medical center and affiliated clinics and a large mid-western health plan using Consumer Assessment of Healthcare Providers and Systems Clinician & Group 1.0 Survey data. Results:Office staff helpfulness and courtesy was perceived more positively for adult than pediatric care in the west coast site. In contrast, more positive perceptions of pediatric care were observed in both sites for coordination of care, shared decision making, overall rating of the doctor, and willingness to recommend the doctor to family and friends. In addition, pediatric care was perceived more positively in the mid-west site for access to care, provider communication, and office staff helpfulness and courtesy. The differences between pediatric care and adult care were larger in the mid-western site than the west coast site. Conclusions:There are significant differences in the perception of care for children and adults with care provided to children tending to be perceived more positively. Further research is needed to identify the reasons for these differences and provide more definitive information at sites throughout the United States.


ObJEctIVES: Kidney biopsy is a valuable tool for both diagnosis and to guide treatment of renal diseases. In this report, we aimed both clinical and pathological evaluation of the kidney biopsies in our institution. MAtErIAl and MEtHODS: Kidney biopsies in adult patients performed between 2002-2011 at the Department of Nephrology were analyzed. Biopsies were performed with the guidance of ultrasonography, and 16 and 18 G needles for two cores were used. At least seven glomeruli and one artery was accepted as adequate for diagnosis. rESultS: Five hundred thirty six kidney biopsy reports was evaluated. The mean age of the patients at presentation was 42.80±16.66 years (16-85 years old), and 55.4% of the patients was male. The most frequent indication of the kidney biopsies were nephrotic range proteinuria with 63.43%. The most common histopathological diagnosis in primary and secondary glomerular diseases was membranous nephropathy (n=88, 16.4%) and amyloidosis (n=96, 17.9%) respectively. The most frequent diagnosis of the biopsies performed due to acute kidney injury was rapidly progressing glomerulonephritis (n=20, 3.7%). The major complication rate was low (0.18%). cOncluSIOn: Nephrotic range proteinuria was the most frequent indication for the kidney biopsy in our institution. Membranous nephropathy and amyloidosis were the most frequent primary and secondary glomerular diseases. Complication rate in percutaneous kidney biopsy with the guidance of ultrasonography is low. kEY wOrDS: Acute kidney injury, Chronic kidney disease, Glomerulonephritis, Proteinuria, Renal biopsy doi: 10.5262/tndt.2012.1002.11


We examined the role of feature matching in motion perception. The stimulus sequence was constructed from a vertical, 1 cycle deg–1 sinusoidal grating divided into horizontal strips of equal height, where alternate strips moved leftward and rightward. The initial relative phase of adjacent strips was either 0° (aligned) or 90° (non–aligned) and the motion was sampled at 90° phase steps. A blank interstimulus interval (ISI) of 0 to 117 ms was introduced between each 33 ms presentation of the stimulus frames. The observers had to identify the direction of motion of the central strip. Motion was perceived correctly at short ISIs, but at longer ISIs performance was much better for the non–aligned sequence than the aligned sequence. This difference in performance may reflect a role for feature correspondence and grouping of features in motion perception at longer ISIs. In the aligned sequence half the frames consisted of a single coherent vertical grating, while the interleaved frames contained short strips. We argue that to achieve feature matching over time, the long edge and bar features must be broken up perceptually (segmented) into shorter elements before these short segments can appear to move in opposite directions. This idea correctly predicted that overlaying narrow, stationary, black horizontal lines at the junctions of the grating strips would improve performance in the aligned condition. The results support the view that, in addition to motion energy, feature analysis and feature tracking play an important role in motion perception.


Macrobrachium is one of prawn genera which has largest species number in family Palaemonidae, with some species of this genus being important commodity in aquaculture. Morphological characters for identification of this genus depend on environmental condition, growth phase, sex, and social dominance. This makes morphological identification on this genus quite difficult and tricky. Alternative approaches are required for better methods of Macrobrachium identification. DNA barcoding using 16S mitochondrial rRNA appears to be one promising method for Macrobrachium identification. This research aims to identify Macrobrachium from Tegenungan Waterfall using morphological and molecular analysis. Samples were taken from 4 sampling sites beneath the waterfall. All specimens were identified using several morphological identification methods. Specimen CR 07a and CR 10 were identified using molecular method. The molecular analysis utilized 16Sar (5'-CGCCTGTTTATCAAAAACAT-3') as forward primer and 16Sbr (5'-CCGGTCTGAACTCAGAT-CACGT-3') as reverse primer. From 11 specimens, 10 were identified as Macrobrachium . Specimen CR 07a was identified morphologically as M. horstii . According to BLAST analysis, specimen CR 10 was recognized as M. horstii with similarity up to 99% to GenBank specimens (JF310718.1 dan FM986616.1). Specimen CR 07a only reach 97% similarity to both GenBank specimens. Genetic distance analysis between specimen CR 07a and CR 10 assumed high genetic diversity, or even cryptic species indication in M. horstii population of Tegenungan Waterfall.


Oral cavity cancer is sixth most frequent cancers in the world. The oral cavity is constantly under the influence of external food and drinks, as well as substances such as alcohol, tobacco products, nicotine, and dental materials. Antioxidants terminate the chain reaction caused by free radicals of oxidation reaction, preventing cell damage or death of the cells. Antioxidants such as α and β carotene, pro- vitamin A, vitamin C, vitamin E, zinc, selenium and spirulina are believed to have a preventive role against oral cancer. Maintaining a good balance of oxidants and antioxidants is very essential for maintaining oral health.


The highly specialized feeding apparatus of modern birds is characterized in part by paraglossalia, triangular bones or cartilages in the tongue that constitute part of the rarely fossilized hyobranchial apparatus. Here, we report on a new, juvenile specimen of the ankylosaurid dinosaur Pinacosaurus grangeri Gilmore, 1933 that provides the first evidence of paraglossalia outside of crown group Aves. The specimen is remarkable in preserving a well-ossified hyobranchial apparatus, including paired paraglossalia, first and second ceratobranchials, epibranchials, and evidence of a median cartilaginous basihyal. Reassessment of Edmontonia, another ankylosaur, also reveals evidence of bony paraglossalia. Ankylosaur paraglossalia closely resemble those of birds, but are relatively larger and bear prominent muscle scars, supporting the hypothesis that ankylosaurs had fleshy, muscular tongues. The other hyobranchial elements, surprisingly, resemble those of terrestrially feeding salamanders. Ankylosaurs had reduced, slowly replacing teeth, as evidenced from dental histology, suggesting that they relied greatly on their tongues and hyobranchia for feeding. Some curved, rod-like elements of other dinosaur hyobranchia are reinterpreted as second ceratobranchials, rather than first ceratobranchials as commonly construed. Ankylosaurs provide rare fossil evidence of deep homology in vertebrate branchial arches and expose severe biases against the preservation and collection of the hyobranchial apparatus. In light of these biases, we hypothesize that paraglossalia were present in the common ancestor of Dinosauria, indicating that some structures of the highly derived avian feeding apparatus were in place by the Triassic Period. © 2015 The Linnean Society of London


The present research study assesses the accuracy of the SRTM X band DEM with respect to high accuracy photogrammetric Digital Elevation Model (DEM) for parts of the Himalaya. The high resolution DEM was generated for Manali and nearby areas using digital aerial photogrammetric survey data of 40 cm Ground Sampling Distance (GSD) captured through airborne ADS80 pushbroom camera for the first time in Indian Himalayan context. This high resolution DEM was evaluated with Differential Global Positioning System (DGPS) points for accuracy assessment. The ADS80-DEM gave root mean square error (RMSE) of ~<1m and linear error of 1.60 m at 90 % confidence (LE 90) when compared with the DGPS points. The overall RMSE in vertical accuracy was 73.36 m while LE 90 was 75.20 m with regard to ADS80 DEM. It is observed that the accuracy achieved for part of Himalayan region is far less as compared to the values officially claimed. Thus, SRTM X band DEM should be used with due care in mountainous regions of Himalaya.


Polish municipalities have the competence to initiate and guide own socio-economic development. Local public investment is a particularly important factor that supports the development of every municipality. However, local public investment depends on several conditions, including the current socio-economic status of a municipality, which in turn is influenced by the municipality's investment activity. The investment activity pursued by municipalities, as suggested by many authors, is of special importance in the development of municipalities situated in both socially and economically less developed areas, such as Eastern Poland. The purpose of this study has been to identify the determinants of investment activity carried out by municipalities situated in the provinces of Eastern Poland, in the context of local socio-economic development and the efficiency of local governments, and to assess the strength and direction of relationships between these determinants and the investment activity of municipalities. A multiple linear regression method was chosen to identify determinants of investment activity, as it enables the user to assess the presence of a relationship between a response (dependent) variable and explanatory (independent) variables as well as the strength and direction of such relationships. The time period for most of the analysed variables spanned the years from 2004 to 2020, and the territorial scope was composed of municipalities located in the Polish provinces: Lubelskie, Podkarpackie, Podlaskie, Swictokrzyskie and Warminsko-Mazurskie. The study confirmed that the investment activity of municipalities depends on factors involved in local socio-economic development. Among these factors, the ones that play a significant role in the municipalities situated in Eastern Poland's provinces are demographic issues, especially internal migrations, economic activity, unemployment and other budget expenses which are competitive to investment outlays, for example expenditure on education and upbringing, or on social welfare. The factors mentioned above implicate the areas worthy special attention of local authorities for the sake of attaining improved socio-economic development of a given area.


Background:Randomized controlled trials (RCTs) suggest that the efficacy of tenofovir-based preexposure prophylaxis (PrEP) strongly depends on the consistency of PrEP use. We explore how the patterns of pill taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention. Methods:A 2-arm RCT was simulated by mathematical models assuming that the prescribed daily doses were skipped periodically, randomly, or in large blocks. Risk-driven adherence, in which PrEP was taken when sex was expected, was also investigated. Three temporal PrEP protection profiles were explored: long (5 days), intermediate (3 days), and short (24 hours). Modeling results were compared to the efficacy observed in completed RCTs. Results:The expected PrEP efficacy was 60% with periodic, 50% with random, and 34% with block adherence when PrEP had a long protection profile and pills were taken only 50% of the days. Risk-driven pill taking resulted in 29% and 37% daily pills taken and efficacy of 43% and 51%, respectively, for long protection. High PrEP efficacy comparable with that observed in Partners PrEP and Centers for Disease Control and Prevention Botswana trials was simulated under long protection, high overall adherence, and limited block pill taking; the moderate efficacy observed in iPrEx and Bangkok trials was comparable with the 50% adherence scenarios under random pill taking and long protection. Conclusions:Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken. When PrEP retains protection for longer than a day, pill-taking patterns can explain a broad range of efficacies observed in PrEP RCTs.


It has been known since 1924 that a proportion of females in the butterfly H. bolina produce only daughters, whereas others produce a 1:1 sex ratio. The present results confirm this, and show also that occasionally a few males are produced. The production of broods with a disturbed sex ratio is inherited entirely through the female line. By sexing the embryos and larvae cytologically and observing mortality in the embryos and late pupal stage we have obtained evidence that the deficiency of males is due to their very high mortality in the pre-adult stage. It is suggested that the abnormal sex ratio is due to an infective cytoplasmic factor (the presence of spirochaetes, as in Drosophila, having been ruled out), in contrast to Acraea encedon where meiotic drive of the Y chromosome has been postulated. The view is put forward that the polymorphism in H. bolina is maintained by the 'infected' females being at a slight disadvantage and that their numbers are maintained by contagion from an unidentified reservoir species.


Objectives and study Fulminant liver failure (FLF) is a syndrome defined by a rapid decline of hepatic function, characterised by jaundice, coagulopathy (INR> 1.5) and hepatic encephalopathy in patients with no evidence of prior liver disease. After viral hepatitis, liver injury due to toxins and drugs is the most common aetiology of FLF in children. In our country mushroom poisoning is frequent, especially in rural area where the socioeconomic status is low. Acetaminophen is probably the most used analgesic/antipyretic drug in our country and causes severe hepatic necrosis (sometimes after suicidal overdoses). The aim of our study was to analyse the main causes of toxic FLF in children hospitalised in our hospital during the last 16 years. Methods We have analysed retrospectively all patients who developed FLF after mushrooms/drugs exposure, hospitalised between January 2000 and October 2016 in our hospital, the main Toxicology Centre in Nord-Western Romania. Results During the last 16 years, 99 cases were admitted to our clinic with FLF after toxic ingestion (85 cases secondary to mushrooms ingestion and 14 cases after drugs exposure). During 2000–2012 the leading cause of FLF was accidental mushrooms poisoning. During the last years the number of cases of voluntary drugs ingestion increased. The mean age of patients with mushroom poisoning was 7.82 years compared with 16.4 years for children who ingested drugs. FLF was more frequent in 2001 (32 cases) and 2010 (16 cases). During the last 5 years the number of drug-induced FLF increased dramatically: 14 cases (one case in 2012, two cases in 2013, three cases in 2014 and four cases each in 2015 and 2016). The most commonly drug involved was acetaminophen (12 cases), the other cases being with FLF induced by valproate (one case) and colchicine (one case). The mortality was increased (46.5%) despite the intensive care management, but without the possibility of liver transplantation: 45 cases with mushroom poisoning and only one after Colchicine exposure. Conclusions FLF due to mushroom poisoning is associated with a high mortality in children, despite optimal medical therapy but without emergency liver transplantation. FLF due to mushrooms poisoning in children was present more frequent between 2001 and 2010. Fortunately, in the last 4 years the incidence of mushrooms intoxications decreased in our area. In the same time, cases with drug-induced FLF increased due to voluntary drug overdoses among adolescents.


In the third of three related papers, the authors discuss rules and mechanisms that could facilitate the expansion of the North American Free Trade Agreement (NAFTA) and promote freer trade and investment in the Americas. These mechanisms include macroeconomic policies that open trade and capital flows, and institutional policies that specify standards and requirements to protect investments and lower risks.


A prescreening system for the early detection of uterine cancer was developed. For the diagnosis of each input specimen (PAP-stained), a figure of malignancy has to be calculated automatically. Methods, problems and results of the system are summarized in this paper. Some thousand microscopic subfields of a specimen are successively scanned by an optimized TV-camera with high spatial resolution. The automated specimen analysis can be described by a two step procedure: single cell classification and evaluation of cell population. For the single cell classifier only features derived from the nucleus are used. The pattern recognition procedures are based on a processor-oriented strategy, and can be adapted to other cytological specimen. The algorithms have been tested with 3 . 10(5) cell images of about 300 specimens.


In 2016 the United States Preventive Services Task Force (USPSTF) updated their screening recommendations for colorectal cancer (CRC). In 2002 they initially recommended CRC screening for the average -risk population, but had insufficient evidence to recommend an age to begin or end screening, or to recommend any particular test or interval of testing. For their 2008 update of the 2002 recommendation, the USPSTF requested a decision analysis using two of the three CRC models funded by the NCI9s Cancer Intervention and Surveillance Modeling Network (CISNET) to inform the ages to begin and end screening, and intervals of testing. Based on the evidence review and decision analysis, in 2008 the USPSTF again recommended CRC screening, this time from ages 50 through 75, and listing the following recommended strategies: colonoscopy every ten years, flexible sigmoidoscopy ever five years with intermittent fecal occult blood test (FOBT), or annual high sensitivity FOBT. For the 2016 recommendations, the USPSTF once again requested a decision analysis from CISNET. This time, all three CRC CISNET models were used to inform the recommendation process. The models were tasked with evaluating the benefits, burden, and harms of CRC screening strategies, estimating the optimal ages to begin and end screening, and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden. Ages to begin screening included 45, 50, and 55 and ages to end included 75, 80, and 85. Screening modalities, or combinations of modalities, included seven strategies: a high sensitivity guaiac-based fecal occult blood test (gFOBT), a fecal immunochemical test (FIT), a multi-target stool DNA test that includes a FIT (FIT-DNA), flexible sigmoidoscopy (SIG), flexible sigmoidoscopy with interval gFOBT (SIG+gFOBT), flexible sigmoidoscopy with interval FIT (SIG+FIT), computed tomographic colonography (CTC), and colonoscopy. Screening intervals varied by modality. Full adherence for all strategies was assumed. CISNET modeled 204 unique screening strategies for a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis. Estimates of test sensitivity were based on a literature review by the Evidence Practice Center. Benefits were modeled in terms of LYG compared with no screening; burden in terms of the lifetime number of colonoscopies required; and harms in terms of the lifetime number of colonoscopy complications. Ratios of incremental burden and benefit (efficiency ratios) were also calculated per 1,000 40-year olds. While the three CISNET colorectal cancer models differed slightly in terms of the absolute benefits and harms of screening, they yielded consistent rankings of screening strategies. Strategies with screening beginning at age 50 generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55. There were limited empirical data to support a start age of 45. For persons adequately screened up to age 75, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50-75, 4 strategies yielded a comparable balance of LYG and screening burden and similar LYG: colonoscopy every 10 years; sigmoidoscopy every 10 years with annual FIT; CTC every 5 years; and annual FIT. Because CTC generally requires cathartic bowel preparation comparable to that required for colonoscopy, we performed an additional analysis in which we used the number of cathartic bowel preparations as the proxy for harms and burden, rather than the number of colonoscopies. With this metric, CTC was not included as a recommended strategy because its efficiency ratio (i.e., ΔCathartic Preps / ΔLYG) exceeded that of colonoscopy. The USPSTF posted a draft recommendation statement (RS) in September 2015 for a public comment period. This draft RS made a distinction between "recommended" and "alternative" testing strategies. Recommended—included colonoscopy every 10 years, annual FIT, annual sensitive gFOBT, and flexible sigmoidoscopy every 10 years with annual FIT. Alternative—included CTC every 5 years and FIT-DNA every 3 years. However the public comments overwhelmingly found this distinction to be confusing and the USPSTF decided to modify their recommendations for clarity. The final RS dropped the "alternative" category and created a single category of "screening tests". The top line "A" recommendation was to screen between the ages of 50 and 75, with any of the screening tests listed. The USPSTF also gave a "C" recommendation for screening between the ages of 76-85. This "C" recommendation means that screening in this age group should be an individual decision based on a patient9s overall health and prior screening history. It is stated that adults in the age group who have never been screened for CRC are more likely to benefit. Clinical questions arise in applying these new recommendations. This includes how to adequately discuss the 7 recommended screening strategies in order for patients to make an informed decision. Also clinicians need to consider how to monitor best choices for those over 75, especially those without prior screening who would benefit most from screening. Citation Format: Ann G. Zauber. Decision analysis for colorectal cancer screening recommendations. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA14.