Abstract
 The DNA-localizing fluorochrome DAPI (4′, 6-diamidino-2-phenylindole) and chicken erythrocytes standard (RBC) were used with image analysis and static microspectrophotometry to estimate nuclear DNA contents in 14 species and varieties of Dictyotales from the Atlantic Ocean (Spain and USA) and the Mediterranean Sea (Spain). Negligible differences were found between specimens fixed in Carnoy's solution (EtOH) and methanol-Carnoy's (methacarn). Present and previously published nuclear DNA content estimates expand our database to include 17 species and varieties representing seven genera with a 2C range of 0.7 – 1.7 pg. Intraplant variation (endopolyploidy) was observed in most isolates and 8C nuclei were quantified in five species. In four species, fluorescence intensity (If) levels in 2C gametophyte nuclei were found to closely approximate 50% of 4C values in vegetative cells of mature sporophytes, consistent with meiosis and a sexual life history in diplobiontic algae. Availability of consensus higher-level phylogenetic trees for Dictyotales has opened the way for determining evolutionary trends in DNA amounts. Both estimated genome sizes and published chromosome numbers for Dictyotales suggest that evolution in the order was accompanied by multiple, discrete polyploidy events which are largely obscured by subsequent small scale loss or gain of chromosomes (aneuploidy). Members of the genus Dictyota are characterized by a narrow range of 2C genome sizes (0.7–0.9 pg) relative to other Dictyotales investigated (1.0–1.7 pg).


We present a method for the isolation and off‐line isotope analysis of formate and acetate in marine samples. Organic acids are separated by high performance liquid chromatography and collected in glass Exetainer® screw‐capped vials that have been prespiked with an oxidant and flushed with helium. The vials are subsequently heated to convert the organic compounds to CO2 for radiocarbon and δ13C analysis. Small aliquots are sampled for measurement of δ13C by isotope ratio mass spectrometry, whereas the majority of the CO2 is saved for radiocarbon analysis by accelerator mass spectrometry using a gas ion source. Accurate δ13C and radiocarbon values were obtained for formate and acetate standards spiked into deep seawater and saline Milli‐Q water at concentrations of 25 to 1000 µM C. The process blank associated with the isolation of formate for radiocarbon analysis was ~1.5 µg C and stable over time. Accurate results could be obtained for marine samples with only 25 µM formate. The radiocarbon analysis of acetate showed significantly higher and more variable extraneous carbon contributions, particularly for samples spiked into seawater. Potential improvements that may make the method appropriate for the radiocarbon analysis of acetate in seawater are discussed. The blanks associated with the wet chemical oxidation were assessed independently and found to be small and consistent (<0.3 µg C), potentially making this approach feasible for a broader set of compounds separated by HPLC for radiocarbon analysis.


Audible tones in noise generated by building mechanical equipment can be a leading cause of complaints from occupants. A number of metrics have been developed to quantify prominence of a tone, but previous work has shown that the impact of a certain tonality appears to vary with the level of the broadband noise signal. More work on how tonal signals of varying tonality, tone frequency and broadband noise levels relate to annoyance and task performance is needed. This paper investigates such relationships between current noise metrics, annoyance and task performance under assorted tonal noise conditions through subjective testing. Participants rated their perceived annoyance after being exposed to noise signals with differing levels of tones while solving Sudoku puzzles. In addition to assessing annoyance, the test also surveyed the perceived workload caused by the noise by using a modified noise-induced task load index questionnaire. Five levels of tonal prominence for each of two tonal frequencies were added above two different ambient background noise levels to create 20 noise signals of interest. The task performance results based on the Sudoku puzzle answers show trends of decreasing accuracy with increasing tone strengths, but the differences are not statistically significant. Other findings are that loudness metrics are most highly correlated with annoyance responses, while tonality metrics demonstrate relatively less but also significant correlation with annoyance. Generally, participants felt more annoyed with higher background noise levels, lower tone frequency and more prominent tone strength. Based on correlation analysis, a multiple regression model using two of the most strongly correlated noise metrics, ANSI loudness level and tonal audibility, has been developed for predicting annoyance responses from tonal noise conditions.


Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.


Historians have regularly debated whether advertisements can be used as a viable source to study the past. Their main concern centered on the question of agency. Were advertisements a reflection of historical events and societal debates, or were ad makers instrumental in shaping society and the ways people interacted with consumer goods? Using techniques from econometrics (Granger causality test) and complexity science (Adaptive Fractal Analysis), this paper analyzes to what extent advertisements shaped or reflected society. We found evidence that indicate a fundamental difference between the dynamic behavior of word use in articles and advertisements published in a century of Dutch newspapers. Articles exhibit persistent trends that are likely to be reflective of communicative memory. Contrary to this, advertisements have a more irregular behavior characterized by short bursts and fast decay, which, in part, mirrors the dynamic through which advertisers introduced terms into public discourse. On the issue of whether advertisements shaped or reflected society, we found particular product types that seemed to be collectively driven by a causality going from advertisements to articles. Generally, we found support for a complex interaction pattern dubbed the consumption junction. Finally, we discovered noteworthy patterns in terms of causality and long-range dependencies for specific product groups. All in, this study shows how methods from econometrics and complexity science can be applied to humanities data to improve our understanding of complex cultural-historical phenomena such as the role of advertising in society.


Effect of illumination and external electric field on thermal expansion of TlGaSe2 crystals has been investigated. Strong transformation of negative linear expansion coefficient has been observed. It is supposed that two main mechanisms are responsible for observed effects: formation of electret state and reverse piezoelectric effect. The electronic nature of negative linear expansion of TlGaSe2 crystals has been proved for the first time.


Distant supervision assumes that any sentence containing the same entity pairs reflects identical relationships. Previous works of distantly supervised relation extraction (DSRE) task generally focus on sentence-level or bag-level de-noising techniques independently, neglecting the explicit interaction with cross levels. In this paper, we propose a hierarchical contrastive learning Framework for Distantly Supervised relation extraction (HiCLRE) to reduce noisy sentences, which integrate the global structural information and local fine-grained interaction. Specifically, we propose a three-level hierarchical learning framework to interact with cross levels, generating the de-noising context-aware representations via adapting the existing multi-head self-attention, named Multi-Granularity Recontextualization. Meanwhile, pseudo positive samples are also provided in the specific level for contrastive learning via a dynamic gradient-based data augmentation strategy, named Dynamic Gradient Adversarial Perturbation. Experiments demonstrate that HiCLRE significantly outperforms strong baselines in various mainstream DSRE datasets.


A method is demonstrated for writing long grating phase masks, which can be used for patterning large-area (square meter size) submicron-period gratings. The method consist of illuminating a small area transmission grating phase mask by a continous wave transverse-electric-polarized collimated laser beam under the −1st order Littrow mounting to define a high-contrast interferogram composed of fringes. By sliding a long photoresist-coated substrate under this small area phase mask, gratings of arbitrary length may be written, with grating lines oriented in the scan direction. The patterning of uninterrupted gratings with lengths exceeding 300 mm is demonstrated.


The Blackstone's Guides Series delivers concise and accessible books covering the latest legislation changes and amendments. Published within weeks of an Act, they offer expert commentary by leading names on the effects, extent and scope of the legislation, plus a full copy of the Act itself. They offer a cost-effective solution to key information needs and are the perfect companion for any practitioner needing to get up to speed with the latest changes. The Department of Trade and Industry has been conducting a major revision of consumer credit law over the past few years. Its proposals on substantial changes to existing law were contained in its White Paper published in December 2003: Fair, Clear and Competitive - The Consumer Credit Market in the 21st Century. Since then, this programme has been implemented by a series of new statutory instruments and a major new Consumer Credit Act which runs to 70 sections and revolutionises the present law and practice of consumer credit. The new Act principally amends the Consumer Credit Act 1974, which is the statute governing the licensing of, and other controls on, traders concerned with the provision of credit or the supply of goods on hire or hire-purchase to individuals. Significant changes brought in by the new Act include the following; DT The re-definition of "consumers" whose agreements are to be regulated by the Act and financial ceilings on consumer credit and hire agreements removed DT The consequences of trading without a license are to be made more severe and the whole process of licensing to be modernised DT Consumer credit is to be brought within the remit of the Financial Ombudsman This Guide covers all of these new provisions, together with the growing importance of the internet and electronic technology to this area of the law, whilst also placing the new Act in the context of what has gone before. The commentary in the Guide is structured in a clear and logical way, thus enabling readers to quickly access the information they require.


2012's Superstorm Sandy had a devastating impact on the New York City metropolitan region, including the suburban Long Island coast and the New Jersey shore. Given the size, density, complexity, and diversity of the region, many approaches have been used to address poststorm recovery. Planning has been central to these efforts. Using in-depth interviews with recovery stakeholders, this analysis of the planning responses to Sandy illustrates what an emergent model of resilient recovery planning looks like and highlights the kinds of resources and approaches that help facilitate this approach. We argue that preexisting planning capacity, strong political leadership, and nongovernmental funding support were critically important aspects of resilience-focused Sandy recovery planning processes.


Equation solving is an important part of school mathematics curricula. Equations are also important in the use of Computer Algebra Systems (CAS). Sometimes a CAS offers an answer that is somewhat different from the answer that is probably expected by the student or teacher. (The customs and requirements for answers can also differ between regions or even teachers.) The expected answer and the answer offered by a CAS could be equivalent or non-equivalent. The gap between the answers could be bridgeable in an instructive manner. These (somewhat unexpected) answers could serve as a catalyst for rich mathematical discussion (see (Pierce and Stacey, 2010)). In this study, over 60 equations (linear, quadratic and fractional equations, equations that contain an absolute value of an expression, irrational, exponential, logarithmic, trigonometric and literal equations) were solved using different CAS. Many answers offered by the CAS coincide with the expected answers. This paper focuses on the answers that deviated from expectations in some form. We considered the following questions in case of each of those answers: Is the answer offered by a CAS equivalent to the answer required at school? Would it be easy for a student, working manually, to transform the answer into the required form? How about if the student uses a CAS? In this context it is important to analyze potential instructiveness such situations. What issues could be raised for discussion? Some of them seem to be relevant in a school context: for example, the properties of different functions (like square root, logarithmic or trigonometric functions). Some issues, e.g., pertaining to infinity, could be beyond the regular school level. The aim is to present a spectrum of possible differences and to highlight the situations (equations, CAS) in which a particular type of discrepancy could occur.


A partial equilibrium, duality-based empirical model is used to measure the tariff and nontariff barrier effects on fresh tomato prices, quantities, and labour demand in Florida, USA, and Sinaloa, Mexico. Reduced-form estimates indicate that the US unit tariff has increased agricultural labour demand in Florida while reducing field labour demand in Mexico. Nontari:ff barriers have had a less significant impact on labour demand. Product heterogeneity may account for varying nontariff barrier impacts on fresh tomato supplies and derived labour demand. Linkages between Mexican agricultural labour supply and Florida agricultural labour demand require further analysis.


This paper deals with the energy efficiency (EE) maximization problem in multiple-input multiple-output two-way relay networks with simultaneous wireless information and power transfer. The network consists of a multiple-antenna amplify-and-forward relay node which provides bidirectional communications between two multiple-antenna transceiver nodes. In addition, one of the transceivers is considered battery limited and has the capability of energy harvesting from the received signals. Assuming the network EE as the objective function, we design power splitting factor and optimum precoding matrices at the relay node and two transceivers. The constraints are transmit power of the nodes, harvested energy and quality of service of two transceivers. The resulting non-convex optimization problem is divided into three sub-problems which are then solved via an alternation approach. In addition, sufficient conditions for optimality are derived and the computational complexity of the proposed algorithm is analyzed. Simulation results are provided to evaluate the performance and confirm the efficiency of the proposed scheme as well as its convergence.


Software development sometimes requires to statically predict the quantity of resources—such as memory and time—that is needed to execute a program. The difficulties of manual resource analysis led to extensive research on automatic methods for quantitative resource analysis. Recently we developed an automatic amortized analysis to compute polynomial resource bounds for first-order functional programs at compile time. Its basis is a type system that augments types with resource annotations. The analysis system is integrated in the programming language Resource Aware ML. Our experiments with a prototype implementation show that the analysis efficiently computes precise time and heap-space bounds for many example programs. In this paper I demonstrate how a user can employ Resource Aware ML to analyze the worst-case time behavior of the sorting algorithms quick sort, insertion sort and merge sort. To illustrate pros and cons, I compare our automatic analysis to a manual analysis of the algorithms in a standard textbook. The paper is divided into three sections. Section 1 motivates the research on static resource analysis. Section 2 briefly introduces Resource Aware ML. Finally, Section 3 contains the actual case study on sorting algorithms.


Pathological myopia is one of the leading causes of blindness worldwide. The condition is particularly prevalent in Asia. Unlike myopia, pathological myopia is accompanied by degenerative changes in the retina, which if left untreated can lead to irrecoverable vision loss. The accurate diagnosis of pathological myopia will enable timely intervention and facilitate better disease management to slow down the progression of the disease. Current methods of assessment typically consider only one type of data, such as that from retinal imaging. However, different kinds of data, including that of genetic, demographic and clinical information, may contain different and independent information, which can provide different perspectives on the visually observable, genetic or environmental mechanisms for the disease. The combination of these potentially complementary pieces of information can enhance the understanding of the disease, providing a holistic appreciation of the multiple risks factors as well as improving the detection outcomes. In this study, we propose a computer-aided diagnosis framework for Pathological Myopia diagnosis through Biomedical and Image Informatics(PM-BMII). Through the use of multiple kernel learning (MKL) methods, PM-BMII intelligently fuses heterogeneous biomedical information to improve the accuracy of disease diagnosis. Data from 2,258 subjects of a population-based study, in which demographic and clinical information, retinal fundus imaging data and genotyping data were collected, are used to evaluate the proposed framework. The experimental results show that PM-BMII achieves an AUC of 0.888, outperforming the detection results from the use of demographic and clinical information 0.607 (increase , ), genotyping data 0.774 (increase , ) or imaging data 0.852 (increase , ) alone. The accuracy of the results obtained demonstrates the feasibility of using heterogeneous data for improved disease diagnosis through our proposed PM-BMII framework.


The Metropolitan Zone of Mexico City with an approximate surface area of 7854 square kilometers, is located in the Valley of Mexico whose boundaries are marked by four mountainous masses that form a basin with hollows and plains. There are more than 29 million people and an approximate of 9 million registered automobiles in the Metropolitan Area. Furthermore, Mexico City is the principal industrial center in the Country with more than 46,000 industries, among them we find cement, metal processing and chemical plants. Sampling of respirable particles PM2.5 was done using an Airmetrics Minivol Portable Sampler and the mass of particles was determined gravimetrically. Particles samples were collected during 24 hours from Monday to Tuesday and from Thursday to Friday. The data of particles concentrations were correlated with the wind velocity and relative humidity. The particles were collected during the years 2004 to 2006 and 2008 to 2012 excepting the year 2007, obtaining a total of 323 samples. Sampling showed that PM2.5 concentration has been increasing through the years of monitoring. Since 2011, PM2.5 concentration has registered a considerable rise when compared with previous years, possibly due to the increase in the vehicle fleet in the Metropolitan Zone of Mexico City, according to data obtained by INEGI. The relative humidity remained at a range from 40 to 80%, during all the years of the sampling campaign, by comparing relative humidity against PM2.5 concentration, it was observed that the higher the relative humidity, the lower the PM2.5 concentration.


We present an unusual complication of chronic tophaceous gout in a 63-year-old man with a 27-year history of gout, who could not be treated with allopurinol due to previous allopurinol-induced neutropenia. The patient presented with a progressively enlarging, painful mass on the bottom of his right foot, which caused difficulty wearing shoes and walking. Extirpation of the tophus and first metatarsophalangeal joint arthroplasty were successfully employed for management of this condition.


This chapter describes contemporary strategies for selective catalytic intermolecular functionalization of the benzimidazole scaffold. Functionalization at nitrogen and position C-2 is well developed employing copper, palladium, rhodium, nickel, and cobalt catalysis. Direct CH activation is the predominant approach to C-2 functionalization. Nickel-based catalysts can activate C—O bonds in conjunc-tion with C—H activation at benzimidazole which grants access to a very broad range of phenols and enols as convenient functionalization precursors in this chemistry. The remaining carbon positions of benzimidazoles are typically functionalized via a sequential halogenation/coupling strategy to ensure selectivity. A key success factor in enabling these chemistries has been the fine-tuning of catalyst-ligand combinations.


Annie Oakley was an American icon. Born in the backwoods of Ohio, she grew up supporting her poor family with game she shot with her dead father's rifle. She proved a natural markswoman and launched a career in show business after she was discovered by Buffalo Bill Cody's Wild West Show. She wowed audiences with target shooting, trick shots, daring horse riding and plenty of flair. She married another marksman, Frank Butler, and theirs was a life-long partnership of shooting together, travelling together, and performing from small towns in Ohio to the grand cities of Europe. Annie collected fans easily, becoming the adopted daughter of Sitting Bull who gave her the name, "Little Sure Shot," shaking hands with the Prince and Princess of Wales and performing for the German Kaiser in a special exhibition where she is said to have shot a cigarette from his hand. The travelling Wild West show helped foster the myths of frontier western life that endure in American consciousness even today. Annie Oakley, who established herself as an American original and made herself famous in a man's world, is a fascinating slice of that process. Her myth has endured in the form of movies, books, TV shows and plays. Sue Macy presents her compelling story through a fascinating readable text, extraordinary historical photographs, and quotes from Annie's own writings and speeches. An afterword helps put Annie in modern context. An index, chronology, and bibliography make for easy reference.


Little policy or practice directly relates to the wellbeing of siblings of young offenders and only a scattering of services are in place which engage the siblings of young offenders by means of positive activities or constructive family support. A review of policies in England and Wales reveals that few services have been designed to address a young person's needs arising directly from sibling imprisonment. It comes as little surprise that much of the relevant service provision targets siblings of offenders indirectly, or as one of a number of target groups, and evidence of policy that directly concerns the siblings of those -in the criminal justice system remains scant. Where services have been designed specifically for young people with a sibling in custody, they tend to relate to the young person's own risk of offending rather than the effect on their welfare of their sibling being imprisoned. Although a growing body of research has acknowledged that the siblings of young people in custody do have specific and additional welfare needs in reality, few support mechanisms are implemented to address those needs.


Purpose: Atypical protein kinase Cι (PKCι) is an oncogene in non–small cell lung cancer (NSCLC). Here, we identify four functional gene targets of PKCι in lung adenocarcinoma (LAC), the most prominent form of NSCLC. Experimental Design: Three independent public domain gene expression data sets were interrogated to identify genes coordinately expressed with PKCι in primary LAC tumors. Results were validated by QPCR in an independent set of primary LAC tumors. RNAi-mediated knockdown of PKCι and the target genes was used to determine whether expression of the identified genes was regulated by PKCι, and whether these target genes play a role in anchorage-independent growth and invasion of LAC cells. Results: Meta-analysis identified seven genes whose expression correlated with PKCι in primary LAC. Subsequent QPCR analysis confirmed coordinate overexpression of four genes (COPB2, ELF3, RFC4, and PLS1) in an independent set of LAC samples. RNAi-mediated knockdown showed that PKCι regulates expression of all four genes in LAC cells, and that the four PKCι target genes play an important role in the anchorage-independent growth and invasion of LAC cells. Meta-analysis of gene expression data sets from lung squamous cell, breast, colon, prostate, and pancreas carcinomas, as well as glioblastoma, revealed that a subset of PKCι target genes, particularly COPB2 and RFC4, correlate with PKCι expression in many tumor types. Conclusion: Meta-analysis of public gene expression data are useful in identifying novel gene targets of oncogenic PKCι signaling. Our data indicate that both common and cell type–specific signaling mechanisms contribute to PKCι-dependent transformation.


The superior mesenteric artery (SMA) provides vital blood supply to the midgut, and an acute abnormality can rapidly precipitate bowel ischemia and infarction and lead to morbidity and mortality. Vascular diseases that acutely compromise the SMA threaten its tributaries and include occlusion, dissection, aneurysm rupture, pseudoaneurysm, vasculitis, and SMA branch hemorrhage into the bowel. Emergency medicine physicians rely on the radiologist to identify SMA abnormalities, to characterize them, and to detail findings that guide the appropriate triage of these patients. As such, radiologists must be cognizant of the features that influence patient treatment to assist vascular surgeons and interventional radiologists in decision making. Some patients can be treated medically, while clinical and radiographic findings may suggest the need for interventional or surgical repair of the artery. In the latter case, multidetector CT findings aid in determining which of the various surgical and endovascular treatment options is optimal, and both vascular and gastrointestinal sequelae of acute SMA abnormalities contribute to these determinations. The authors review acute life-threatening conditions involving the SMA including acute occlusion, dissection, aneurysm, pseudoaneurysm, and hemorrhage and discuss the vascular and gastrointestinal multidetector CT findings in each of these conditions that help to guide surgical and interventional management. ©RSNA, 2019.


Using DNA barcoding markers, we inferred the phylogenetic relationships of the genus Anacyclus including for the first time the three Eastern Mediterranean species, A. anatolicus , A. latealatus and A. nigellifolius . Our results conclusively reveal the polyphyletic condition of this genus in its current circumscription. The molecular data show that A. anatolicus , A. latealatus and A. nigellifolius do not belong to Anacyclus. According to the current knowledge of the Anthemideae systematics, these three species should be placed within the genus Cota and thus the new combinations Cota anatolica, Cota latealata, and Cota nigellifolia are proposed. Such a taxonomic placement is congruent with the achene morphology and biogeography although the circumscription of Cota itself requires further studies.


Abstract Conclusion: Specific immunoglobulin E (IgE) reactivity towards the major mugwort allergen Art v 1 is a good indicator for Art v sensitization. Allergens from the ragweed species Amb t and Amb a possibly share common IgE-binding epitopes. Objective: The aim of this study was to investigate the reactivity pattern of IgE in Chinese patients with weed pollen-induced allergic rhinitis. Methods: Sera from 50 weed pollen-induced allergic rhinitis patients were tested for specific serum IgE reactivity against allergenic extracts of mugwort (Artemisia vulgaris, Art v), short ragweed (Ambrosia artemisiifolia, Amb a), giant ragweed (Ambrosia trifida, Amb t), and single allergens of Art v 1, Art v 3, Amb a 1, and profilin. Results: Sera from 88% of the patients demonstrated positive specific IgE reactivity to Art v, and of these 82% were positive to Art v 1. Sera from 38% of the patients showed positive specific IgE reactivity to both ragweed species Amb t and Amb a. A strong correlation was found between the specific IgE levels of Amb t and Amb a. Of the Amb a IgE-positive patients, 38% were positive for Amb a 1. Of all patient sera tested, 12% were specific IgE-positive to profilin.


OBJECTIVES
This paper employs statistical methods to identify the factors associated with modes of delivery and delivery assistance in rural areas of Bangladesh. The principal objective of this paper is to suggest various policy options on the basis of study findings in order to provide guidelines to improve the overall delivery-related morbidity conditions in Bangladesh.

METHODS
This study analyzes data from a followup study conducted by the Bangladesh Institute of Research for Health and Technologies (BIRPERHT) on maternal morbidity in rural Bangladesh in 1993. A total of 1020 pregnant women were interviewed in the followup component of the study. For the purpose of this study, we selected 993 pregnant women with at least one antenatal followup.

RESULTS
It is observed that the mode of delivery is complicated (assisted or destructive) if the pregnancy is either first or fifth or higher order and if bleeding occurred during the antenatal period. More educated respondents, high-risk pregnancies, pregnancies with past history of anemia and respondents who reported marriage at a relatively higher age receive assistance from trained personnel at a significantly higher proportion. Some of the important findings are: (1) first pregnancy or fifth or higher prior pregnancies and hemorrhage during pregnancy increase the risk of assisted or destructive modes of delivery; and (2) first or fifth or higher prior pregnancies are more likely to seek assistance from trained health personnel; similarly, regular antenatal visits and past history of anemia are also positively associated with seeking assistance from trained personnel. However, still there is a substantial proportion of women who remain at risk of complicated deliveries assisted by untrained personnel, posing a formidable challenge to policymakers.

CONCLUSION
The results indicate several policy options: (1) the high-risk group, first or fifth or higher pregnancies, need special care and the existing health management system may be strengthened to create awareness among potential mothers for seeking appropriate measures from the beginning of pregnancy; (2) antenatal followup can be emphasized for high-risk pregnancies, and for respondents with a past history of anemia and other complications, a realistic referral system can be developed; (3) the campaign for increased age at marriage and increased age at first birth needs to focus the health issues more extensively; and (4) education for women needs to be given very high priority in order to bring about a lasting impact on the overall health condition of women.


Typestate reflects how the legal operations on imperative objects can change at runtime as their internal state changes. A typestate checker can statically ensure, for instance, that an object method is only called when the object is in a state for which the operation is well defined. Prior work has shown how modular typestate checking can be achieved thanks to access permissions and state guarantees. However, typestate was not treated as a primitive language concept: typestate checkers are an additional verification layer on top of an existing language. In contrast, a typestate-oriented programming (TSOP) language directly supports expressing typestates. For example, in the Plaid programming language, the typestate of an object directly corresponds to its class, and that class can change dynamically. Plaid objects have not only typestate-dependent interfaces but also typestate-dependent behaviors and runtime representations. This article lays foundations for TSOP by formalizing a nominal object-oriented language with mutable state that integrates typestate change and typestate checking as primitive concepts. We first describe a statically typed language—Featherweight Typestate (FT)—where the types of object references are augmented with access permissions and state guarantees. We describe a novel flow-sensitive permission-based type system for FT. Because static typestate checking is still too rigid for some applications, we then extend this language into a gradually typed language—Gradual Featherweight Typestate (GFT). This language extends the notion of gradual typing to account for typestate: gradual typestate checking seamlessly combines static and dynamic checking by automatically inserting runtime checks into programs. The gradual type system of GFT allows programmers to write dynamically safe code even when the static type checker can only partly verify it.


ii Abstract Oral sustained release drug delivery system is being widely used for the past two decades as a means to provide a drug with improved therapeutic efficacy and also to assure rational drug therapy. The sustained release dosage form allows slow release of the drug followed by the maintenance of a constant therapeutic blood or tissue drug levels for an extended period of time. This characteristic of the dosage form further decreases frequency of drug intake ensuring better patient compliance and often reduces adverse effects associated with drug. The aim of the present study was to design and develop an optimized once daily oral sustained release matrix tablet formulation of a potent nonsteroidal anti-inflammatory drug (NSAID), Ketorolac Tromethamine. Ketorolac Tromethamine has a short biological half-life of 4 to 6 hours, so it was considered as a suitable drug for the formulation of sustained release tablet to prolong its therapeutic action and reduce dosing frequency. The experiment was designed to develop nine different formulations of matrix tablets by using combination of hydrophilic Methocel K100M CR and Methocel K4M CR polymers at different ratios. The selection of the excipients was based on IR and DSC studies depending on the compatibility of which the tablets were manufactured by direct compression. The resulting tablets were evaluated for physical properties such as weight variation, hardness, thickness, friability and drug content which complied with the limits specified in USP. In vitro dissolution study was performed in order to obtain the drug release profile of the matrix tablets and the outcomes were fitted into various mathematical models for release kinetic analysis. Most of the formulated tablets were found to follow Higuchi drug release kinetics and exhibited non-Fickian type drug release mechanism. Furthermore, in order to obtain an optimum product, a 3 full factorial design was employed to systematically optimize the drug release profile with Design Expert software. The analysis of the responses produced by the software revealed that the polymer combination used at different ratios has control on the drug release. F4 was selected as the optimum formulation significantly on the basis of desirability criterion and graphical analysis.


The effect of prestress on dislocation (and inclusion) fields in nonlinear elastic solids is analysed by extending previous solutions by Eshelby and Willis. Using a plane-strain constitutive model (for incompressible incremental nonlinear elasticity) to describe the behaviour of ductile metals (J2-deformation theory of plasticity), we show that when the level of prestress is high enough that shear band formation is approached, strongly localized strain patterns emerge, when a dislocation dipole is emitted by a source. These may explain cascade activation of dislocation clustering along slip band directions.


This thesis explains how Sir Hersch Lauterpacht constructed his international legal theory in the universalisation process of the European law of nations. Introduction presents the general background of the universalisation process of the European law of nations. Chapter 1 discusses the situationality of Lauterpacht, which affected his life as an international lawyer, namely his Jewish background, the influence of Kelsen and the English tradition of international law. Lauterpacht's normative conception of the international community in the inter-war period is explicated in Chapter 2. hi Chapter 3,1 examine how Lauterpacht dealt with legal problems in the outlawry of war from the inter-war period to the end of the Second World War. Chapter 4 holds Lauterpacht's attempts to reconstruct the international community after World War E. Being opposed to political realism, Lauterpacht employed the Grotian Tradition in order to prove the historical value of his idealism. He moulded the function of states into the framework of his normative conception of the international community as civitas maxima with regard to recognition, collective security and the international protection of human rights. I demonstrate how Lauterpacht contributed to the work of the International Law Commission in Chapter 5 from 1952 to 1954. Chapter 6 examined the problems of the responsibility of international judges, namely their neutrality, legal reasoning, and the compatibility of' automatic' reservation with the ICJ Statute. The conclusion is an appreciation of legalism within the framework of the universalisation of international law in the era of decolonisation


Abstract The paper shows that, if two conditions are satisfied, both radial contraction and concertina trade tax reforms continue to be desirable in a small open economy that differs from the one usually considered by having distributional objectives and using distortionary taxes to raise revenue. The first condition is that some optimisation in the choice of commodity taxes takes place - at a minimum, taxes on nontraded goods must be optimally chosen while taxes on traded goods keep the consumer prices of such goods constant. The second is that pure profits are absent from every household's budget constraint. These conditions mean that some care is required in arguing the case for simple trade tax reforms in small open economies.


Ten communication sessions were delivered. Scenarios were created following conversations with real patients and staff. Multidisciplinary facilitation, including a senior nurse, communication specialist, foundation programme director, simulation fellows and simulated patients set up and managed the sessions. Patient presence was also available during these sessions. Four scenarios were used; comforting a patient following unwelcome news, discussion with a relative regarding treatment for a patient lacking capacity; communicating with a colleague after disclosure of domestic abuse and challenging unprofessional behaviour. Participants rotated in multi-disciplinary groups of four ensuring that they were exposed to all scenarios and facilitators. Within these small groups, participants would take turns to engage with the actor and observe their colleagues doing likewise, encouraging all to interact during the debrief. Facilitator and actor also provided feedback. The richness of multidisciplinary feedback (doctors feeding back to nurses and vice versa) was a factor new to all participants and regarded positively. Written feedback was obtained. 74 participated; 47 doctors and 26 nurses. Feedback demonstrated this model provided a valuable learning opportunity enjoyed by the multi-disciplinary groups involved. The sessions reinforced the importance of good multi-disciplinary communication as a core value within healthcare professional codes of conduct as well as promoting a culture of compassionate care for the future.


G protein-coupled receptors (R) exist as homo- or hetero-oligomers, which is essential for receptor function. Since BK actions were blocked by a Mas R antagonist or that Ang-(1-7) responses disappeared when the BK receptor B2 was blocked, we hypothesized that Mas and B2 Rs on the plasma membrane may interact through hetero-oligomer formation. Our aim was to investigate the existence of heteromerization between Mas and B2 Rs by the fluorescence energy transfer (FRET) technique and the functional consequences of this oligomer formation. HEK293T cells were transfected with the coding sequence for Mas R fused to YFP and B2 R fused to CFP. After 48 h cells were incubated in the absence and presence of 1 μM Ang-(1-7) or BK during 15 min and interaction between Mas and B2 R was evaluated by FRET. Functional consequences of this interaction were determined by ligand binding assays. A positive FRET was observed in cells cotransfected with MasR-YFP and B2R-CFP, suggesting that both Mas and B2 Rs interact by a hetero-oligomer formation in a constitutive manner. This hetero-oligomer was not altered by the agonist because FRET was not modified when the cells were stimulated with BK or Ang-(1-7). Ang-(1-7) or BK induced internalization of this hetero-oligomer into early endosomes since MasR-YFP or B2R-CFP colocalized with Rab-5, an early endosome marker, after ligand stimulation. When MasR-YFP plus B2R-CFP transfected cells were stimulated with Ang-(1-7) there was a decrease of 82±6% in Mas R and 58±4% in B2 R present in the plasma membrane. Conversely, when MasR-YFP plus B2R-CFP transfected cells were stimulated with BK there was a decrease of 91±4% in B2 R and 53±3% in Mas R in the plasma membrane. This result clearly demonstrates that in co-expressing cells of both receptors the selective stimulation of one of the GPCRs promotes co-internalization of both receptors. We conclude that Mas and B2 Rs constitutively interact through an hetero-oligomer formation at the plasma membrane which may explain the cross-talk between Ang-(1-7) and BK. This hetero-oligomer is internalized upon stimulation with either Ang-(1-7) or BK, leading to a decrease in the number of Rs present in the membrane.


Introduction Post-menopausal women and men with iron deficient anaemia (IDA) require investigation because they harbour a risk of underlying pathology such as cancer (1). We have demonstrated that in patients with colorectal symptoms referred from primary care an undetectable Faecal Haemoglobin (FHb), measured by a Faecal Immunochemical Test (FIT), can be a 'rule-out test' for underlying significant bowel disease (2). We wished to examine whether measurement of FHb could assist in the assessment of patients referred from primary care with IDA. Method We prospectively recorded all referrals to the NHS Tayside Colorectal Service from December 2015 – September 2016. GPs were encouraged to request FIT at point of referral in all patients. We used each patients unique Community Health Index number (CHI) to link GP referrals to laboratory results, OGD and colonoscopy findings. The WHO definition of IDA was used (3). FHb concentrations were grouped into undetectable (<10 µg/g), detectable and >400 µg/g for purposes of analysis. Results 3272 patients were referred. 416 were referred as IDA of which 397 were verified; of these, 214 submitted a FIT test. To date 191 patients have undergone endoscopic procedures. 161 have had both an OGD and colonoscopy. An additional 26 have had OGD only and 3 have had colonoscopy only. At colonoscopy, 26 (15%) had significant bowel disease; 15 had CRC, 9 High-risk adenoma (HRA) and 2 Inflammatory Bowel Disease ( IBD). At OGD, 2 had Upper Gastrointestinal Cancer (UGIC). 116/191 (60%) had undetectable FHb; of these, 5% had significant GI disease (2 had CRC and 4 had HRA). Using a cut-off of 'undetectable' FHb (<10 µg/g), gave Negative Predictive Values of 98%, 96%, 100%,100% for CRC, HRA, IBD, UGIC. respectively. 75/191 (39%) had detectable FHb; of these 13 (17%) had significant disease; 4 CRC, 5 HRA, 2 IBD, 2 UGIC. 15/164 (7%) had FHb >400; of these 9 (60%) had significant bowel disease (9 CRC). A detectable FHb gave a Positive Predictive Value of 37.1% for CRC rising to 50% for any significant bowel disease. Conclusion Measurement of FHb is of benefit in the assessment of IDA. As concentrations rise, the likelihood of significant underlying GI disease increases from 5% (undetectable) to 39% (detectable) to 60% (very high). Those with high concentrations of FHb should be prioritised for urgent investigations as the likelihood of significant pathology is high. Disclosure of Interest None Declared


The SMaRT Messenger Pilot Project is an extension of a previous collaboration between Nottingham Community Housing Association (NCHA) and Loughborough University. Research at the university has contributed to the development of a device by which messages can be sent to the television screens of older and vulnerable people. For example, such messages might: • Alert them to take medication • Remind them of appointments • Send them information of interest • Communicate with friends and family This research project has two objectives. NCHA would like to use the SMaRT Messenger system as a commercial product to enhance their service for their clients and to market to other agencies. Loughborough University, on the other hand, is interested in the digital inclusion of older and vulnerable people and the use of a television based messenger system to facilitate communication and Information to that portion of society. This one year study has investigated the utility of the device as perceived by participants in three different locations served by NCHA. A three phase survey was conducted of people who are testing the system in their own homes. A subgroup of participants was questioned through SMaRT messenger and five people were interviewed face to face. The system has been designed to enable communication between people who receive support from NCHA in their own home and NCHA staff, family and friends and other relevant services. The target audience is people who are not highly competent users of digital communication, such as emails or social media sites, and who have underlying or deteriorating health conditions, live independently with a strong functional support system. The findings indicate that a television based messenger system is an important way of communication for such a limited audience, giving them the feeling of reassurance and inclusion in society.


Objective: To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology. Methods: We analyzed 18F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 age-matched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period. Results: Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression. Conclusions: Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD.


This paper stems from a fieldwork I carried on for a period of ten months in a CAS (Centre for extraordinary hospitality) for asylum seekers where I played a double role, both as reception operator and as researcher. Through some ethnographic descriptions my purpose is twofold: on one hand I mean to analyze how the emergency paradigm leads to control and compassion politics, both aimed at a securitarian management of asylum seekers; on the other my work highlights how the awareness achievement process of asylum seekers' rights turned them into active players, thus deconstructing the image of passive victims. Finally, by examining my position in the Nicara Center, I would like to suggest some considerations upon the role of the anthropologist, who is to be considered not only in the field of ethnographic analysis, but also as an active player in everyday emergencies thanks to his reflective and critical qualities on anthropological knowledge, which are essential in order to promote a different kind of reception by acting as direct witness and no longer as simple observer. Based on this premises, my main objective is that of analyzing how the anthropological knowledge can be intended not only towards observation aimed at understanding security and power balances, but also towards a change in the context by promoting a kind of anthropology ready to implement social interventions which deconstruct emergency logics and, at the same time, capable of preserving its theoretical depth and self-reflective dimension.


The purpose of a core list of periodicals is to organize and rank publications that correspond to unique information needs, while satisfying the definition and scope of a field of study. For the past twenty-five years, the Association of Architecture School Librarians' Core List of Architecture Periodicals has served as a collection development guide for librarians supporting programs accredited by the National Architectural Accrediting Board (NAAB). Compiled and vetted by professional librarians and architecture faculty, the list has also informally become an information resource assessment standard for NAAB teams. Now in its fifth edition, the list is unique to the discipline in that no other professional organization publishes an alternative. This article describes the review process, evaluative methods, and criteria applied to develop that edition. In doing so, it outlines the process to develop such a resource for an academic program granting a professional design degree.


endometrial-myometrial junction, presence of the ''bright edge'' sign at the edges of the lesions, and preservation of normal endometrial lining adjacent to the lesion. Patient clinical history and histological assessment of tumor grading were assessed. Results: 79 cases were analyzed, 26 were benign and 53 cases malignant. Antero-posterior lesion diameter was 8.89 ± 5.58, 14.8 ± 6.99, and 20 ± 10.57 millimeters for the benign, low grade and high grade malignancy lesions respectively, which was statistically significant (P < 0.05). High echogenicity, cystic formation within lesions, presence of ''bright edge'' and preservation of normal endometrium adjacent to the endometrial lesion were significantly more common in the benign group as compare to malignant lesions (P < 0.05). Complex echogenicity and loss of endometrial-myometrial junction were significantly more common in the malignant lesions group (P < 0.05). These parameters could not distinguish between low and high grade endometrial malignancy. Conclusions: Malignant endometrial lesions are associated with larger antero-posterior diameters. Sonographic parameters such as high echogenicity, cystic formation, presence of ''bright edge'' and preservation of normal endometrium might be used to distinguish between benign and malignant lesions. These parameters should be assessed, while considering a surgical intervention for endometrial lesions.


>> Twelve years ago, Peter Frost called upon us to consider why compassion counts. More than a decade later, we can see, feel, and understand why compassion counts both in the field of organizational studies and in our lives as scholars. As he was so many times during his career, Peter was prophetic in identifying and animating a core idea that is central to our field and to our lives. We approach this essay with three goals in mind, all focused on elaborating how compassion is a generative force. By generative, we mean that compassion as an idea opens up new vistas, expands resources, and creates new insights (Carlsen & Dutton, 2011). It is a force in the sense that it propels and motivates action. Given these definitions, we hope this essay achieves three goals. First, we aspire to celebrate the generative capacity of compassion by illustrating the wisdom and insight contained in compassion stories, and in particular in one of Peter's compassion stories. Second, we invite reflection on the meaning of being a compassionate scholar through immersion in stories about Peter left by his colleagues after he died. Third, we discuss how compassion alters our focus, our work, and our imagination in organizational studies. Together, we hope all three angles on how compassion counts celebrate the contribution that Peter's article is continuing to make in our field and in our lives.


Most sequence-to-sequence (seq2seq) models are autoregressive; they generate each token by conditioning on previously generated tokens. In contrast, non-autoregressive seq2seq models generate all tokens in one pass, which leads to increased efficiency through parallel processing on hardware such as GPUs. However, directly modeling the joint distribution of all tokens simultaneously is challenging, and even with increasingly complex model structures accuracy lags significantly behind autoregressive models. In this paper, we propose a simple, efficient, and effective model for non-autoregressive sequence generation using latent variable models. Specifically, we turn to generative flow, an elegant technique to model complex distributions using neural networks, and design several layers of flow tailored for modeling the conditional density of sequential latent variables. We evaluate this model on three neural machine translation (NMT) benchmark datasets, achieving comparable performance with state-of-the-art non-autoregressive NMT models and almost constant decoding time w.r.t the sequence length.


The aim of this article is to analyse the syntactic and semantic interclausal relations that hold with Old English verbs
 of inaction. These verbs are studied from the perspective of juncture-nexus relations and the semantic relations Phase, Psych-action and
 Causative. The results are compared on the grounds of the Interclausal Relations Hierarchy. The comparison of semantic content and syntactic
 expression evidences discrepancies between too weak juncture-nexus types, such as clausal subordination, and very close semantic relations,
 like Phase. Two main conclusions are drawn. Firstly, the Interclausal Relations Hierarchy allows us to describe the variation in the
 complementation of inaction verbs in Old English; and to make predictions on the diachronic axis, given that the loss of finite clause
 complementation and the change to infinitival complementation presented by Present-Day English verbs of inaction are fully predicted by the
 IRH. Secondly, semantic relations and nexus types remain stable throughout the change, whereas juncture levels change.


ABSTRACT Cosmopolitanism is often seen as a western concept associated with liberal individualistic values. It is also associated mostly with the urban educated middle-class. However, cosmopolitan thinking has been also prevalent in the East. Scholars in the twenty-first century are increasingly arguing that, there are multiple ways of thinking about cosmopolitanism originating from different regions of the world. Among Eastern thinkers, Rabindranath Tagore from colonial British India has been considered by many as one of the most cosmopolitan thinkers. The uniqueness about Tagore's cosmopolitanism is that, it did not uproot him from his rural Bengali roots and sense of ethnic identity. He was very much a "rooted-cosmopolitan". In his book, 'Cosmopolitanism: Ethics in a world of strangers', Kwame Anthony Appaiah had agued that, a "rooted cosmopolitan" is someone who was rooted in his own cultural context while having an open-mind to feel literally at home in the world. This article draws on archival research at Rabindra Bhawan in Shantiniketan and University of Illinois, Urbana-Champaign Library archives to further this argument and demonstrates how Tagore's school and university were built drawing on his "rooted cosmopolitan" ideals and international mindedness. In conclusion, this article highlights some of the challenges of sustaining the reformist educational institutions led by Tagore's unique personality traits, social and pedagogic reform movements in the nineteenth century and early twentieth century colonial British India.


It is often argued that the increased labor market participation of seniors threatens family support provided to dependent elderly people. The purpose of this paper is to assess the causal effect of retirement on the frequency of care provided by individuals aged 55-69 years to their elderly parent. Using data from the Survey of Health, Aging and Retirement in Europe (SHARE), we estimate an endogenous switching model that allows the retirement effect to be heterogeneous with respect to observed and unobserved characteristics. To tackle the possible endogeneity of selection into retirement, we use the heterogeneity of retirement rules between and within European countries. On average, being retired does not significantly impact the probability of providing care but significantly increases the frequency of care conditional on being caregiver. The same pattern is observed regardless of the individual observed characteristics, even if the provision of informal care appears to be less sensitive to the retirement status when the child cannot rely on the other parent to provide care or when both parents are in poor health. These results suggest that pension system reforms should not affect the number of caregivers. Some adverse effects on the intensity of involvement among caregivers are nevertheless expected.


The Dolphin and Union caribou herd ( Rangifer tarandus groenlandicus ) is of great importance for Inuit subsistence and cultural needs. This herd is somewhat particular in that it relies on the seasonal connectivity of the sea ice between Victoria Island and the mainland to undertake its fall and spring migrations to and from its wintering ground on the mainland. While the herd may have numbered in the order of 100 000 animals in the past, it experienced a dramatic decline in the early 1900s and stopped its migration to the mainland. It resumed its migration only as it started to increase during the 1980s and 1990s, and in October 1997, the caribou gathered on the southern coast (prior to crossing to the mainland) were estimated to number 27 948 ± 3367 SE. In October 2007, using the same method and covering approximately the same area as during the 1997 survey, we estimated 21 753 ± 2343 SE caribou within our study area. The method used in 1997 and 2007 assumes that most of the herd is located within a narrow strip along the southern coast of Victoria Island, but also acknowledges that some caribou are outside that area. Therefore, we undertook a correction of both 1997 and 2007 estimates for the Dolphin and Union caribou herd based on available data from radio-tracking of female caribou. The corrected estimate for the Dolphin and Union caribou herd in 2007 was 27 787 ± 3613 SE. Both the study area estimates and the corrected herd estimates for 1997 and 2007 indicate that the herd trend in the intervening decade was at best stable.


Idiopathic lung fibrosis (IPF) is a fatal lung disease characterized by chronic epithelial injury and exhausted repair capacity of the alveolar compartment, associated with the expansion of cells with intermediate alveolar epithelial cell (AT2) characteristics. Using SftpcCreERT2/+: tdTomatoflox/flox mice, we previously identified a lung population of quiescent injury-activated alveolar epithelial progenitors (IAAPs), marked by low expression of the AT2 lineage trace marker tdTomato (Tomlow) and characterized by high levels of Pd-l1 (Cd274) expression. This led us to hypothesize that a population with similar properties exists in the human lung. To that end, we used flow cytometry to characterize the CD274 cell-surface expression in lung epithelial cells isolated from donor and end-stage IPF lungs. The identity and functional behavior of these cells were further characterized by qPCR analysis, in vitro organoid formation, and ex vivo precision-cut lung slices (PCLSs). Our analysis led to the identification of a population of CD274pos cells expressing intermediate levels of SFTPC, which was expanded in IPF lungs. While donor CD274pos cells initiated clone formation, they did not expand significantly in 3D organoids in AT2-supportive conditions. However, an increased number of CD274pos cells was found in cultured PCLS. In conclusion, we demonstrate that, similar to IAAPs in the mouse lung, a population of CD274-expressing cells exists in the normal human lung, and this population is expanded in the IPF lung and in an ex vivo PCLS assay, suggestive of progenitor cell behavior. CD274 function in these cells as a checkpoint inhibitor may be crucial for their progenitor function, suggesting that CD274 inhibition, unless specifically targeted, might further injure the already precarious lung epithelial compartment in IPF.


Cloud certifications are a good means to assure users of high level of security and reliability of certified cloud services. However, cloud environments are highly dynamic due to the challenging cloud characteristics and fast technology life-cycles. We believe that current certifications fail to cope with an everchanging cloud environment because assessments are based only on manual expert assessments and periodic spot checks. We argue that continuous service certification (CSC) is required to assure reliable and trustworthy cloud services. To understand and enhance CSC's rate of adoption, we examine the adoption process of CSC from the perspective of certification authorities by building on the Diffusion of Innovations theory and the Technology-Organization-Environment framework. Our findings reveal that the innovation's characteristics, organizational and environmental influences will affect the adoption of CSC by certification authorities. We advance the understanding of the CSC adoption process by providing a synthesis and discussion of important factors.


Kevin Rudd has taken up where he left off, but the vexing question of asylum seekers is yet to be answered by either party, writes Anthony Ashbolt. It is almost as if Kevin Rudd never stopped being Prime Minister. Such is the surreal nature of politics I referred to in the last piece. I noted also the Hollywood-like imagery the leadership battle evoked. Yet I did not mention the most glaring instance of this. Gillard marched into the caucus room that would decide her fate surrounded by a posse of loyal colleagues, only to be followed by the lone ranger Kevin Rudd. Disciplines Arts and Humanities | Law Publication Details Anthony Ashbolt, Refugees a 'political whipping boy', [Blog], Illawarra Mercury, 18 July 2013. This journal article is available at Research Online: http://ro.uow.edu.au/lhapapers/866


There is abundant landscape evidence for extensive land reclamation conducted within the Shannon estuary wetlands. To date, little published research is available which identifies how much reclamation has occurred, its timing and the likely environmental implications. This paper addresses these questions on the basis of available cartographic and documentary data on land reclamation in this area. Identification of reclaimed land was based on the 2nd Edition Ordnance Survey of Ireland Map Series of 1924. These maps represent landscape features relating to reclamation, such as embankments, artificial arterial drainage channels and sluices. Using such indicators for the purpose of demarcation, the extent of the lands reclaimed has been mapped. Documentary information on reclamation schemes was acquired from the National Archives files on the Irish Quit Rent Office, including letters, memoranda, draft bills and Government Acts, legal documents and statements of account, and these support and supplement cartographic data. In total, approximately 6,500ha of the Shannon estuary lowlands were reclaimed for agriculture and other purposes. This has significantly altered the morphometric characteristics of the estuary, as embankments and revetments for flood protection have reduced the potential energy dissipation area and the water storage capacity of the estuarine wetlands. Reclamation has resulted in modification of the estuarine physical environment and its hydrodynamics, and altered the character of the wetland habitat in the estuary environs. ADDITIONALINDEXWORDS: estuaries, reclamation, land claim, wetlands, embankments, drainage, cartography, historical evidence Journal of Coastal Research SI 36 365-373 (ICS 2002 Proceedings) Northern Ireland ISSN 0749-0208


Silicon-based nanophotonic waveguides and components fabricated in silicon-on-insulator technology build a platform for high density photonic integrated circuits, where active III–V devices can be incorporated using evanescent field coupling. These circuits can be fabricated with standard CMOS technology processing, allowing for low cost mass production in applications such as optical networks, computer inteconnects and sensing. Connecting of these integrated structures to the real world of optical fibers appears is an important problem to be solved. In this paper we discuss some solutions and present some of fabricated devices including a grating coupler-polarization splitter with over 50% efficiency for both polarizations and a nonuniform grating coupler with 68% efficiency for single polarization. To the best of our knowledge, they are the highest coupling efficiencies obtained by regular SOI grating couplers for both, single polarization and polarization splitting.


It has been proposed that acute eosinophilic pneumonia (AEP), which is characterized by the absence of recurrence, is associated with cigarette smoking (CS), because Japanese patients with AEP are young and have a high incidence of short-term smoking history. However, there has been no direct evidence that CS causes AEP. We hypothesized that tolerance might develop against repeated resumption of smoking cigarettes in CS-induced AEP cases. In this connection, we challenged a patient with CS-induced AEP with repeated resumption of CS, and it was demonstrated that CS induced AEP in conjunction with tolerance to repeated resumption of smoking.


The use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites (aminomethylphosphonic acid) in food for human consumption and pose a threat to health. The effect of these herbicides on the fish organism at the biochemical level has been insufficiently studied. We studied changes in the content of adenine nucleotides, enzyme activity, quantitative indexes of energy metabolism substrates in carp under the action of glyphosate. It has been found that proteins are the major energy substrate under the influence of glyphosate in the liver, brain, white muscle of carp yearlings. Glyphosphate decreases energy metabolism in the brain of carp and increases it in the white muscles. The growth of activity of catabolic enzymes in the liver under the influence of glyphosate can be attributed to the adaptive remodelling of metabolic pathways for homeostasis and enantiostasis in response to herbicides.


The study was conducted to elucidate the determinants of food security among the maize growing rural households of Bogra district. Data were collected from 0 farmers, who were selected using a stratified random sampling method. The sample farmers were classified as small (0.51-1.00 ha), medium (1.01-3.00 ha) and large (above 3.00 ha) according to their possession of land. To collect data, a questionnaire was administered through face-to-face interviews. Data were analyzed using descriptive statistics, food security index and logit model. The results of the study revealed that almost all rural households in Bogra district were food secured. It was checked by using recommended minimum calorie requirement (i.e., 2122 kcal). Based on the results, 20 (33.33 percent)households were found to be food insecured while the rest 40 (66.67 percent)households were food secured households. Thus, only 20 (33.33 percent) of the sampled households could not get the minimum and above recommended calorie level, i.e., 2122 kcal per capita per day. The results of logit model indicated that four variables out of eight have influence on household's food security condition. The factors influencing household food security were found to be age of household head, household size, monthly agricultural income and food expenditure. The results of logit model showed that a unit increase in food expenditure will increase the probability of the household being food secure, households with older heads are more food insecure, household food security decreases with increasing household size, and increased income of household's ensure food security status.


These notes are preliminary reading for the APTS module 'Statistical Asymp-totics' which will take place in Southampton during 23-27 March 2015. Two immediate questions that may come to mind are: (i) What is statistical asymptotics about? and (ii) Why study this topic? For the purposes of this module, the answer to question (i) is that statistical asymptotics is about the study of statistical models and statistical procedures , such as parameter estimation and hypothesis testing, when the sample size n goes to infinity. Properties such as consistency and asymptotic normality of parameter estimates fall within the domain of statistical asymptotics as they entail statements about what happens as n → ∞. There are at least 3 distinct answers to question (ii). 1. Motivating practical approximations. In most statistical models in a frequentist setting, exact inference is not feasible and so there is a need to develop approximations. Asymptotic (i.e. large n) results often provide convenient approximations which are sufficiently accurate for practical purposes. In Bayesian inference, Laplace's method (an asymptotic procedure) often provides useful approximations to posterior distributions. 2. Theoretical insight. Asymptotic analyses often provide valuable theoretical insight into complex models and complex problems. For example, it may help us to identify which aspects of a problem are of most importance. 3. Theories of optimality. There is sufficient mathematical tractability within an asymptotic framework to develop various theories of statistical optimality. We shall not have much to say about optimality in this module; see van der Vaart (1998) for discussion of aspects of optimality. The objectives of the module are: (i) to provide an overview of the first-order asymptotic theory of statistical statistical inference, with a focus mainly on likelihood-based approaches, but with brief consideration of the more general setting of M-estimators; (ii) to provide an introduction to analytic methods and tools, in particular approximation techniques that are potentially useful in applications; (iii) to provide exposure to key ideas in contemporary statistical theory; and (iv) to provide practice in application of key techniques to particular problems.


This LibGuide will provide students with wide ranging resources to explore the ways in which the concept of discovery is represented in and through texts


The Gilgit District and surrounding areas of northern Pakistan are rich in plant and cultural diversity, yet have been poorly studied ethnobotanically. Surveys were conducted to identify medicinal plants being used and their uses. Distribution of knowledge about medicinal plants between men and women and two age classes was examined in order to see who holds knowledge and if knowledge is being retained or lost. Older men and women were found to know more about medicinal plants. 27 species were reported to be used for a range of purposes. The researchers conclude that there is need for development of conservation strategies in the area that will take into account local needs, perspectives and economic development opportunities.


Many companies in the cross section of telecommunication and mobile technology engage in R&D collaborations to manage uncertainty, create synergies and learn. While the challenges of managing individual collaborations are well documented, little is known on how to systematically manage several R&D collaborations simultaneously. We use modern portfolio theory as an analogy to show how companies active in mobile telecommunication manage risks and create synergies by simultaneously engaging in several inter-firm collaborations.


Drug resistance of bacterial pathogens has become a serious problem in healthcare. To overcome resistance, a new generation of antimicrobial compounds based on novel structures is needed. Lanthipeptides are small ribosomally produced peptides that contain so-called lanthionine rings. These peptides often are equipped with antimicrobial activity and are then termed lantibiotics. These lantibiotics may form an alternative to classical antibiotics. This thesis focuses on the development of a generic production system for lanthipeptides. The envisioned production system contains a known lantibiotic modification enzyme and possibly the associated transporter for secretion into the external medium. With the Gram-positive bacterium Lactococcus lactis as a production host, production of a bioactive lantibiotic was realized when expressed together with its cognate modification enzyme and transporter. However, the system turned out to be too specific for its natural lanthipeptide giving poor yields of unrelated lanthipeptides. Therefore, Escherichia coli was used as an alternative host but now for intracellular production skipping the transport step. With this system several lanthipeptides could be produced that underwent the expected modifications. Therefore, E. coli appears a good host for lanthipeptide production with the potential to be developed into a generic system.


This letter presents energy-efficient MgO based magnetic tunnel junction (MTJ) bits for high-speed spin transfer torque magnetoresistive random access memory (STT-MRAM). We present experimental data illustrating the effect of device shape, area, and tunnel-barrier thickness of the MTJ on its switching voltage, thermal stability, and energy per write operation in the nanosecond switching regime. Finite-temperature micromagnetic simulations show that the write energy changes with operating temperature. The temperature sensitivity increases with increasing write pulsewidth and decreasing write voltage. We demonstrate STT-MRAM cells with switching energies of <;1 pJ for write times of 1-5 ns.


The economical situation is constantly changing and competition is forcing companies to become more innovative than ever. Family businesses are thought to be less innovative and stagnant compared to other organizations. Yet, they manage to survive and thrive in this competitive world. Some family businesses have been able to use their unique traditions to obtain competitive advantage. The purpose of this study is to gain insight how family businesses are leveraging on their traditions and how different governing styles affect the process of innovation. Thus, the research question we are trying to answer is How are family businesses with different governance styles exploiting their traditions in their product innovations? This qualitative study is conducted by using case study strategy consisting of a total eight case companies. The data is collected from semi-structured interviews and secondary data. The analysis of the collected data is conducted in five steps, and patterns are formed based on the analysis. Our results showed that companies behaving according to the agency theory perceived tradition as something static. Thus, did not fully take advantage of it. Family businesses behaving according to the stewardship Theory perceived tradition as dynamic and were able to reinterpret it to use it in their product innovation process.


The paper analyses the problems of contemporary entrepreneurship theory which scientists are confronting in recent years. There are arguments given in favour of a broad definition of entrepreneurship as 'emergence of new economic activity'. The starting point of research on entrepreneurship research is the question, 'how, why, and when do entrepreneurial firms explore and exploit entrepreneurial opportunities?' According to the author of this paper, it thus becomes possible to redefine the subject of the discipline, which in turn enables a sustainable development of the theory, and a refocusing on new areas such as social and institutional entrepreneurship. The paper forecasts a shift in research on entrepreneurship beyond Western societies to encompass the so-called transitional economies and emerging markets. These countries have some important contextual differences which affect the practices of entrepreneurship and these are discussed here. Contextual differences justify the importance of investigating new institutions and actors which might become challenging subjects of entrepreneurship theory in future. The paper also discusses the agenda of entrepreneurship research in Russia, explains the reasons for the relatively weak development of Russian entrepreneurship theory, and suggests policies to improve this situation. The author stresses the changes in methods and research design and the new possibilities and empirical data sources resulting from the latest advancements in IT and big data. In particular, more intensive research and demand for this research will likely emerge because of the increasing availability of techniques for collecting and analysing big data. The author anticipates the increasing importance of international comparative studies conducted by large project teams, and of longitudinal projects to elaborate realistic recommendations for civil society, national governments, and international organizations.


: Patients with chronic pain are often depressed, and antidepressants have been widely used in the treatment of these patients. Well controlled clinical studies have shown that antidepressants have analgesic effects, apparently independent of changes in mood, and in lower doses than used in the treatment of depression. Good results have been reported for several types of chronic pain, especially headache and facial pain, arthritis, fibromyalgia and neuralgias. In addition, antidepressants have also an indirect analgesic action by relieving a depressive condition associated with chronic pain.


Titanium dioxide (TiO2) is considered as an inert and safe material and has been used in many applications for decades. TiO2 have been widely studied, due to its interesting general properties in a wide range of fields including catalysis, antibacterial agents, in civil as nano-paint (self-cleaning) and especially photocatalysis, and that affect the quality of life. Thus, the development of nanotechnologies TiO2 nanoparticles, with numerous novel and useful properties, are increasingly manufactured and used. TiO2 doped with noble metal are good candidates in the performance these applications. The fascinating physical and chemical features of TiO2 depend on the crystal phase, size and shape of particles. For example, varying phases of crystalline TiO2 have different band gaps that rutile TiO2 of 3.0 eV and anatase TiO2 of 3.2 eV, determine the photocatalytic performance of TiO2. This chapter explains basic information on TiO2 and theoretical concepts of nanostructure of TiO2 nanoparticles as a semiconductor photocatalyst.


Research in the area of automatic speaker verification (ASV) has advanced enough for the industry to start using ASV systems in practical applications. However, as it was also shown for fingerprints, face, and other verification systems, ASV systems are highly vulnerable to spoofing or presentation attacks, limiting their wide practical deployment. Therefore, to protect against such attacks, effective anti-spoofing detection techniques, more formally known as presentation attack detection (PAD) systems, need to be developed. These techniques should be then seamlessly integrated into existing ASV systems for practical all-in-one solutions. In this paper, we focus on the integration of PAD and ASV systems. We consider the state of the art i-vector and ISV-based ASV systems and demonstrate the effect of score-based integration with a PAD system on the verification and attack detection accuracies. In our experiments, we rely on AVspoof database that contains realistic presentation attacks, which are considered by the industry to be the threat to practical ASV systems. Experimental results show a significantly increased resistance of the joint ASV-PAD system to the attacks at the expense of slightly degraded performance for scenarios without spoofing attacks. Also, an important contribution of the paper is an open source and an online-based implementations of the separate and joint ASV-PAD systems.


We present a novel idea for user authentication that we call pass-thoughts. Recent advances in Brain-Computer Interface (BCI) technology indicate that there is potential for a new type of human-computer interaction: a user transmitting thoughts directly to a computer. The goal of a pass-thought system would be to extract as much entropy as possible from a user's brain signals upon "transmitting" a thought. Provided that these brain signals can be recorded and processed in an accurate and repeatable way, a pass-thought system might provide a quasi two-factor, changeable, authentication method resistant to shoulder-surfing. The potential size of the space of a pass-thought system would seem to be unbounded in theory, although in practice it will be finite due to system constraints. In this paper, we discuss the motivation and potential of pass-thought authentication, the status quo of BCI technology, and outline the design of what we believe to be a currently feasible pass-thought system. We also briefly mention the need for general exploration and open debate regarding ethical considerations for such technologies.


Healthcare sustainability has been dominated by a strong fiscal orientation. In an era of budget cuts and staff reductions, the financial challenges in Canadian healthcare are immediate and must be addressed. However, an independent focus on financial viability is too narrow a framing; too limited to allow for the kind of creative, novel, and even radical thinking that is required to fundamentally alter the current course of healthcare in Canada and internationally. Prospects for solving the current financial challenges are likely to be greatly enhanced if we simultaneously account for the broad and interrelated dimensions of sustainability. What would a healthcare system look like if sustainability were adopted as the focal and principal goal? And what might a "deep" sustainability orientation imply for how we think about and manage healthcare systems? This analysis is informed by the notion that healthcare systems are fully contained within the societal system, which is itself fully contained within the broader ecological system. This model, which foregrounds nature as the most fundamental and important system, has both greater ecological validity and particular relevance to the healthcare context given the interdependence between the health of natural systems and the health of humans. Our understanding of nature in relation to health may be key to solving or at least reducing the economic burden of healthcare. A multidimensional systems orientation thus has the potential to unveil new modes of thinking that highlight intersectoral relations, communications, collaboration, and cross-boundary learning for improved health and wellbeing, healthcare performance, and sustainability.


Background: Patients with acute myeloid leukemia (AML) carry a dismal prognosis due to drug resistant cancer cells that reside in O2 deprived niches of the bone marrow. Here, we sought to interrogate AML drug responses under hypoxic (1% O2) and normoxic (21% O2) conditions in order to identify novel drug targets.
Methods: We utilized RNAseq, PCR and RPPA to interrogate chemotherapy-induced expression responses in M14 cells. We further assessed intracellular cholesterol levels (ICCLs), cell growth and apoptotic cell death per MTT and FACS analysis in AML cell lines and primary cells (PCs) in response to chemotherapy under normoxia and hypoxia.
Results: Cytarabine blunted cholesterol biosynthesis- and induced CD36-mRNA expression under 1% and 21% O2. ICCLs were significantly higher in Cytarabine treated AML cells compared to untreated controls. Treatment with Rosuvastatin significantly inhibited growth of M14, THP1, OCI-AML3 as well as AML PCs (n=3). Further, Rosuvastatin lowered ICCLs and conferred pro-apopotic and growth inhibitory effects against M14 and THP-1 cells. Growth inhibition was enhanced when Rosuvastatin was combined with Cytarabine, yielding additive to synergistic effects. Similar effects were observed in AML PCs (n=10) where Rosuvastatin combined with Cytarabine demonstrated strong synergy.
Conclusion: (i) Depletion of ICCLs is counterbalanced by CD36 expression in Cytarabine-treated AML cells under normoxia and hypoxia. (ii) Rosuvastatin exerts antileukemic activity in AML cell lines and PCs via downregulation of ICCLs, induction of apoptosis and inhibition of cell growth. (iii) Rosuvastatin acts synergistically with Cytarabine against AML cells. Impact: Further investigation of Rosuvastatin  in AML therapy is warranted.


As an experimentalist interested in arteriosclerosis, I look upon diabetes mellitus as a natural experiment in atherogenesis. This narrow view may distress clinicians engaged in the management or prevention of diabetes, but they should agree that progress in the prevention of atherosclerosis will benefit diabetic human beings most of all. In 1947 I began a laboratory study of the effect of experimental diabetes on the development of vascular disease in animals. The premise that the presence of diabetes aggravates the vascular disease is so attractive that even after five years of fruitless work it is sometimes tempting to try again. It was not possible to demonstrate that this was a valid hypothesis. Although certain capillary lesions were demonstrated in diabetic rats, no evidences of major vessel disease were produced in either rats, dogs, or monkeys, whether fed cholesterol or not. A second hypothesis concerning atherogenesis has been studied and contested for almost half a century and yet has eluded the critical experiment which will properly evaluate its verity. In simple terms this hypothesis states that atherosclerosis, a variant of arteriosclerosis, is a consequence of abnormal lipid metabolism. The immediate problems posed are those of describing the kind and extent of abnormal lipid metabolism necessary for this consequence, a description of the contribution or weight of abnormal lipid metabolism in this effect, and finally a description of the mechanism by which the lipid abnormality develops. There is now a great deal of acceptable information on these points, but for the present I shall consider some evidence that my associates and I have obtained in studies of diabetic human subjects. If from the relation of these observations, any suggestions or implications are made for the management of diabetes, they are fortuitous.


Magnetic resonance imaging (MRI) was used to nondestructively observe changes in water content in roots of Pelargonium hortorum x Bailey during a period of relatively rapid transpiration. Anatomical regions of the root could be differentiated with a spatial resolution of 0.1 x 0.1 mm. MRI shows great potential for study of plant-water relations.


We have designed and synthesized a π-conjugated system that consists of a flexible and nonplanar π joint and two emissive rigid and planar wings. This molecular system exhibits respectively red, green, and blue (RGB) emission from a single-component luminophore in different environments, namely in polymer matrix, in solution, and in crystals. The flexible unit gives rise to a dynamic conformational change in the excited state from a nonplanar V-shaped structure to a planar structure, leading to a dual fluorescence of blue and green colors. The rigid and planar moieties favor the formation of a two-fold π-stacked array of the V-shaped molecules in the crystalline state, which produces a red excimer-like emission. These RGB emissions are attained without changing the excitation energy.


The 2022 ImageCLEFmedical caption prediction and concept detection tasks follow similar challenges that were already run from 2017–2021. The objective is to extract Unified Medical Language System (UMLS) concept annotations and/or captions from the image data that are then compared against the original text captions of the images. The images used for both tasks are a subset of the extended Radiology Objects in COntext (ROCO) data set which was used in ImageCLEFmedical 2020. In the caption prediction task, lexical similarity with the original image captions is evaluated with the BiLingual Evaluation Understudy (BLEU) score. In the concept detection task, UMLS terms are extracted from the original text captions, combined with manually curated concepts for image modality and anatomy, and compared against the predicted concepts in a multi-label way. The F1-score was used to assess the performance. The task attracted a strong participation with 20 registered teams. In the end, 12 teams submitted 157 graded runs for the two subtasks. Results show that there is a variety of techniques that can lead to good prediction results for the two tasks. Participants used image retrieval systems for both tasks, while multi-label classification systems were used mainly for the concept detection, and Transformer-based architectures primarily for the caption prediction subtask.


Personalized and emergent instruction is an effective model for Early Childhood Educators (ECEs) and students to consider and use in their own teaching. This workshop utilizes yoga as an experiential and emergent model with ECEs to be reproduced for contextualized and meaningful learning in the early childhood environment. The workshop highlights how children's literacy and personal development can be enhanced by yoga or other personalized sessions with one-time or multiple-session use.
As teachers, it can be advantageous when we bring personal interests into the teaching context. These personal interests can be seen as strengths, hooks, or ways of engaging others in our lessons as well as making learning contextualized and meaningful. We cannot be interested, knowledgeable and 'strong' in every area, but that should not prevent us from bringing in slices of interesting tidbits from many domains to personalize teaching with adults or children. This workshop utilizes yoga in the early child-centered education context to demonstrate how children and early childhood educators can experience literacy and personal development benefits either from a one–time exposure or from repetitive use of personalized sessions.


The N-methyl-D-aspartate receptors (NMDARs) play an important role in synaptic plasticity and excitotoxicity. Physiological activation of NMDARs is associated with synaptic plasticity and neuronal survival, whereas excessive activation of NMDARs contributes to neuronal death. Previous studies suggest that activation of synaptic NMDARs promotes neuronal survival. In contrast, activation of extrasynaptic NMDARs results in neuronal cell death. However, the precise roles of NMDARs at different subcellular locations are not completely understood. Here we present new evidence that activation of extrasynaptic NMDARs alone does not cause neuronal death; whereas co-activation of extrasynaptic and synaptic NMDARS does. Specifically, after blocking synaptic NMDARs with MK801 and bicuculline, higher concentration of NMDA or glutamate activated extrasynaptic NMDARs, but did not lead any significant neuronal death in DIV14 or much older cultures. Consistently, 75 min oxygen glucose deprivation, a cellular ischemic stroke model, did no cause any obvious neuronal death after blockade of synaptic NMDARs. In contrast, without pretreatment of bicuculline and MK801, oxygen glucose deprivation induced 73.6 % cell death. Additionally, we obtained the same conclusion with another protocol, a combination of low dose of NMDA (15 μM, supposed to activate only synaptic NMDARs) and MK801, to block synaptic NMDARs. Further, we show that activation of either synaptic or extrasynaptic NMDARs promoted neuronal survival signaling and did not disturb intracellular calcium homeostasis. However, co-activation of synaptic and extrasynaptic NMDARs led to shut-off of neuronal survival signaling, triggered neuronal death signaling, and disturbed intracellular calcium homeostasis. More importantly, by examining NMDAR-related survival signaling and calcium signaling, we found that activation of extrasynaptic NMDARs requires a higher concentration of ligand, suggesting that extrasynaptic NMDARs have a relative lower ligand affinity compared to synaptic NMDARs. These findings will provide new evidence on the role of extrasynaptic NMDARs, and suggest a new direction for designing neuroprotective drugs to selectively block extrasynaptic NMDARs while leaving synaptic NMDAR functions intact.