The present study is an attempt to understand and highlight the role of media in a culturally diverse society of a border district Poonch of Jammu and Kashmir a state of India. The study is an analysis of the role of media with the main aim to highlight the actual scenario and problems of the society which is a culturally and relatively intermixed district bordering with Pakistan lasting around five decades viz. for the period 1947 to present. Although the scope of this study is not very vast it is a limited one specifically covering a particular area of the of Jammu and Kashmir, but it will be very much helpful for understanding and highlighting the similar problems faced by number of other similar areas of the of the same Union Territory particularly and India generally which are facing many problems due to borders with neighboring countries and also having cultural affinities. The purpose of this study is to spread awareness among the backward and ignorant masses as well as to the authorities so that all the opportunities in this era of information and communication technology are fully utilized to make relation with their near and dear on the both sides of the border. For this media can play a very significant role as it is playing in other areas. But unfortunately even after 70 years of India's independence the backward areas in every sphere are not at par with the other areas. Media is one of the most important tools which can prove for the good governance through e- governance. This study has been undertaken with the help of secondary as well as primary data through quantitative as well as qualitative approaches. Furthermore at the preliminary stage the focus has been paid more on secondary sources of information by reviewing the existing available literature on the subject matter. Primary data has been taken through the living experiences in such areas since childhood and by interviewing scholars, teachers, and students from such areas. It also important to mention here that there is very little information available in existing literature with specificity of the role of media with respect to a bordering, backward and culturally intermixed area of the state of Jammu and Kashmir. Thus it is believed that this study can yield good results and will add something new to the existing literature.


The adoption of inflation targeting in India has been a much debated topic which also becomes a challenge for an emerging economy. Though inflation targeting has already been adopted in some emerging and advanced countries, successful implementation would be a concern. The paper argues that an emerging country like India needs to consider the composition of consumer price index; state of macro econometric models; and young demographics, unemployment rate and lack of social security before adopting inflation targeting. To modernize the monetary policy framework, India could consider introducing regular review of the regional economy; instituting a monetary policy committee; and separating debt from monetary management, the paper argues.


Traffic prediction has been an active research topic in the domain of spatial-temporal data mining. Accurate real-time traffic prediction is essential to improve the safety, stability, and versatility of smart city systems, i.e., traffic control and optimal routing. The complex and highly dynamic spatial-temporal dependencies make effective predictions still face many challenges. Recent studies have shown that spatial-temporal graph neural networks exhibit great potential applied to traffic prediction, which combines sequential models with graph convolutional networks to jointly model temporal and spatial correlations. However, a survey study of graph learning, spatial-temporal graph models for traffic, as well as a fair comparison of baseline models are pending and unavoidable issues. In this paper, we first provide a systematic review of graph learning strategies and commonly used graph convolution algorithms. Then we conduct a comprehensive analysis of the strengths and weaknesses of recently proposed spatial-temporal graph network models. Furthermore, we build a study called STG4Traffic using the deep learning framework PyTorch to establish a standardized and scalable benchmark on two types of traffic datasets. We can evaluate their performance by personalizing the model settings with uniform metrics. Finally, we point out some problems in the current study and discuss future directions. Source codes are available at https://github.com/trainingl/STG4Traffic.


Fluid machines and control elements such as pumps and valves are widely used in marine piping systems. Pumps and valves are the most important hydrodynamic noise sources in piping systems which present low frequencies and broadband characteristics. Mechanical vibration of pumps and valves transmits along the equipment installation bases and pipeline supports, causing hull vibration and thus noise radiation. The hydrodynamic noise of pumps and valves transmits along the pipeline analogically and then radiates to the sea through the open ends. Mechanical vibration and subsequent noise radiation has been effectively controlled to some extent by active and passive isolation methods. Thus, it becomes an urgent task to eliminate noise radiation from the open ends and through the surrounding fluid. The design of a functional fluid pipeline silencer is imperative, and this kind of fluid pipeline silencer should incorporate low frequency and broadband hydrodynamic noise attenuation characteristics. In this paper, some fluid pipeline elastic-shell silencers with different diameters are proposed based on acoustic-elasticity noise reflecting theory. The acoustic characteristics, such as acoustic impedances and transmission losses of the fluid pipeline silencers, including elastic-shell type and traditional perforated expanding cavity type, are both tested based on acoustic impedance testing techniques. Experimental results indicate that transmission loss (TL) of the elastic-shell silencers can reach 10dB at low frequency broadband 20Hz~1000Hz. The DN100 elastic-shell silencer with a more compact structure delivers better noise elimination performance than a traditional perforated expanding cavity silencer. Furthermore, all the elastic-shell silencers with different pipe diameters show excellent noise elimination performance at low frequency broadband. Therefore, the elastic-shell silencers could effectively control the hydrodynamic noise of pumps and valves in seawater cooling pipeline systems and reduce nozzle noise radiation. Excellent low frequency and broadband noise elimination characteristics of elastic-shell fluid pipeline silencers are experimentally validated subsequently. The experimental research in this paper provides the basis for future marine applications.


Wireless sensor networks may be deployed in many applications to detect and track events of interest. Events can be either point events with an exact location and constant shape, or region events which cover a large area and have dynamic shapes. While both types of events have received attention, no event detection and tracking protocol in existing wireless sensor network research is able to identify and track region events with dynamic shapes(NH-change shapes to identities), which arise when events are created or destroyed through splitting and merging. In this paper, we propose DRAGON, an event detection and tracking protocol which is able to handle all types of events including region events with dynamic identities. DRAGON employs two physics metaphors: event center of mass, to give an approximate location to the event; and node momentum, to guide the detection of event merges and splits. Both detailed theoretical analysis and extensive performance studies of DRAGON's properties demonstrate that DRAGON's execution is distributed among the sensor nodes, has low latency, is energy efficient, is able to run on a wide array of physical deployments, and has performance which scales well with event size, speed, and count.


The Water Framework Directive (WFD) of the European Union prescribes "good ecological status" of all waters. In terms of nitrate this means, among other things, to avoid eutrophication and achieve a good ecological balance in surface water systems for the benefit of the groundwater dependent flora and fauna (Hinsby et al. 2012). In Denmark, the nitrate load to estuaries has been nearly halved since the first national action plan was implemented in the mid-1980s, but further abatements are required in many areas to fulfil the WFD. New approaches to regulate nitrate use are needed with measures targeted to the areas where most effect is obtained, and this is recognised at political level. Recent legislation allows farmers to increase nitrate application, but should at the same time introduce new mitigation measures and a more targeted approach to regulation. Therefore the physical system, i.e. the geological framework and topography, of the catchment has to be understood (Winter 1999). Previous studies have shown that in hydrological catchments with high geological variability, sampling of groundwater in riparian zones, the stream water itself and water in the stream bed can help to identify near-stream areas with specific nitrate problems. Detailed studies are, however, not feasible in all catchments, and development of representative typologies to guide an optimal location of mitigation measures in the catchment is thus needed. The present study is a detailed characterisation of nitrate transport and reduction in the groundwater–stream system in the river Hagens Møllebæk catchment for this purpose.


Two morphologically distinct types of murine megakaryocyte (MK) colonies are present after three to seven days in soft agar culture: (a) "big-cell" colonies composed of ten to 30 large, mature-appearing megakaryocytes and (b) "heterogeneous" colonies consisting of approximately 100 or more cells at various stages of differentiation. Cytochemical and immunocytochemical techniques were used to study MK maturation in colonies as well as normal mouse bone marrow. Acetylcholinesterase (AChE), a specific marker for murine platelets and MK, was found in the perinuclear cisterna, endoplasmic reticulum, and occasionally, Golgi cisternae of MK in three-day big-cell colonies and immature bone marrow MK. MK in seven-day big-cell colonies and mature bone marrow MK showed additional reaction sites in the demarcation membrane system and occasional granules. In seven-day heterogeneous colonies, small cells resembled immature bone marrow MK with respect to AChE localization, whereas large cells corresponded to mature bone marrow MK. With immunogold procedures at the ultrastructural level, polyclonal antibodies against human platelet membrane glycoprotein IIIa and antimouse platelet antiserum labeled bone marrow MK and all MK from colonies grown in soft agar cultures for three to seven days. Granulocytes and macrophages in both bone marrow and soft agar cultures were negative for AChE and these immunocytochemical markers. These data indicate that the pattern of expression of AChE during maturation of MK is similar in vivo and in vitro and demonstrate, when using this marker at the fine-structural level, that a greater range of MK maturational stages is present in heterogeneous colonies than is observed in MK in big-cell colonies. Furthermore, we have confirmed that small cells in heterogeneous colonies are MK and that these colonies are composed solely of MK and their precursors.


Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat numerous diseases for over two millennia. It has many advantages compared with other routes. In this article, headspace-solid phase microextraction-gas chromatography-mass spectrometry and high performance liquid chromatography-atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass spectrometry were applied for the first time to analyze the absorbed constituents in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14 monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nine N-alkylamides and eight lignans were tentatively identified in the rabbit plasma and CSF. Thirty-three absorbed constituents are found to have different bioactivities related to the pharmacological actions of AR through bibliography data retrieval. These indicated that many types of constituents of TCM can be absorbed at the nasal cavity into both rabbit blood and CSF. This is the first study to explore the absorption of AR, and comprehensively analyze the absorbed constituents after intranasal administration of TCM. These findings extend our understanding of the effective substances of AR, and inspire us to make a hypothesis on the mechanism of additive effect of multiple constituents of TCMs, which is very worthy of further investigation.


Objective To investigate reciprocal temporal relationships between tobacco consumption and psychological disorders for youth. Design: Review Data sources Five databases (PubMed, Embase, Scopus, CINAHL and PsycINFO) on 26 September 2019 and updated on 11 May 2021, indexing tobacco, mental illness and longitudinal. Study selection: Methods used consensus and multiple reviewers. Interventions Cohort studies (n=49) examining tobacco and selected psychological disorders (depression, anxiety, bipolar, psychosis, borderline personality disorder) among youth, and systematic reviews (n=4) of these relationships met inclusion criteria. Primary and secondary outcome measures Effect of tobacco on psychological disorders and effect of psychological disorders on tobacco. Data extraction and synthesis Independent extraction by the first author and checked by final author. Joanna Briggs Institute Critical Appraisal Tools were used for all studies. Included studies had moderate-to-high appraisal scores. We synthesised findings using vote counting for effect direction and descriptive data. Results Fifty-three studies were included in the review. Thirteen of 15 studies showed a positive effect direction of tobacco on depression (p<0.001). Six of 12 studies showed a positive effect direction of depression on tobacco (p=0.016). Six of eight studies showed a positive effect direction of tobacco on anxiety (p=0.016). Eleven of 18 studies showed a positive effect direction of anxiety on tobacco (p=0.003). No effect between tobacco and bipolar, or tobacco and psychosis was found. No studies examined tobacco and borderline personality disorder. Conclusions Reciprocal relationships existed between tobacco and both depression and anxiety for youth, though causality is unconfirmed. No positive effect direction was found between tobacco and psychosis, perhaps because nicotine has conflicting effects on psychosis. For other relationships examined, evidence was weak because of low number of studies. More research to inform prevention and early intervention is needed. PROSPERO registration number CRD42020150457.


Interhemispheric relations of the EEG power in the 1-60 frequency band were studied at the stages of formation and testing of the cognitive set to facial expression. Different topographic asymmetry patterns were revealed in subjects with different set plasticity. In subjects without behavioral actualization (n = 11) of the set at the stage of set formation, EEG power in the gamma band (21-40 and 41-60 Hz) prevailed in the frontal areas of the right hemisphere, whereas the power of electrical oscillations in the bands of 2-7 and 8-13 Hz was higher also in the frontal areas but of the left hemisphere. At the stage of set testing, this basic topographical asymmetry pattern persisted. Formation of the set in subjects with pronounced actualization (n = 18) was characterized by another topographical asymmetry pattern: a significant excess of the power of gamma oscillations was observed in the posterotemporal and occipital areas of the left hemisphere, whereas the power of oscillations in the bands 2-7, 8-13, and 14-20 Hz was higher also in the posterior areas but of the right hemisphere. No asymmetry in the EEG power was observed in these subjects at the stage of set testing.


Campbell's Lenient Unified Model of Parallel Systems (CLUMPS) is presented, a candidate model of parallel computation which aims to tackle and solve the deficiencies of existing candidate models. It is shown that all parallel computers can perform the same computations, but differ in their ability to support different communication loads. This conclusion is reflected in the definition of CLUMPS which aims to be architecture-independent, reflective of execution costs, expressible and intellectually manageable. It also reflects the principle that if a problem can be partitioned into regions, and if those regions are preserved in the mapping of the algorithm to the architecture then greater communication efficiency can be achieved than if the locality was not preserved. Algorithmic skeletons are seen as high level language constructs capturing parallelism, hence communication, in a regular and manageable manner. Such skeletons can be costed in terms of CLUMPS to provide parallel performance prediction.<<ETX>>


Growing research has examined the association of oral microbiome with pancreatic cancer risk, but results have been inconsistent. Our previous study showed that bacterial taxa known to inhabit the oral cavity were common in the pancreas microbiome, and that bacterial DNA profiles in the pancreas were similar to those in the duodenum tissue of the same subjects regardless of disease state. These data suggest that bacteria may be migrating from oral into the gut and pancreas. We collected oral swabs and at least one pancreatic tissue or intestinal samples from subjects who underwent surgery for pancreatic diseases or diseases and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We then quantified bacterial communities (Amplicon Sequence Variant level) at different body sites, investigated their co-abundance patterns, and analyzed the correlations between microbiome at oral sites and that in pancreatic tissue and intestinal samples using concordance statistics and Pairwise Stratified Association (PASTA) testing. The present analysis included 52 subjects (46% with pancreatic cancer; aged from 31 to 86 years old) contributing a total 324 samples. We identified a total of 73 unique Amplicon Sequence Variants (ASVs) that were shared between oral and pancreatic or intestinal samples. Accounting for pairing and within-subject correlation, 7 ASVs showed significant concordance (Kappa statistics) and 5 ASVs exhibited significant or marginally significant PASTA between oral samples and pancreatic tissue or intestinal samples. Of these, our PASTA analyses identified two specific bacterial species (Gemella morbillorum and Fusobacterium nucleatum subsp. vincentii) that showed consistent presence or absence patterns between oral and intestinal or pancreatic samples. Lastly, our microbial co-abundance analyses showed several distinct ASVs clusters and complex correlation-networks between ASV clusters in buccal, saliva, duodenum, jejunum, and pancreatic tumor samples. Oral, intestinal, and pancreatic microbiomes are correlated. Bacteria of oral origin exhibit co-abundance relationships and demonstrate complex correlation patterns in the intestinal and pancreatic tumor samples. Growing evidence has shown that bacterial species may survive, decline, and adapt as interdependent functional groups. Future studies should aim to uncover the co-abundance of specific microbial communities for studying etiology of microbiota-driven carcinogenesis in prospective and longitudinal studies. Citation Format: Mei Chung, Naisi Zhao, Richard Meier, Devein C. Koestler, Erika Del Castillo, Guojun Wu, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud. Oral, intestinal, and pancreatic microbiomes are correlated and exhibit co-abundance in patients with pancreatic cancer and other gastrointestinal diseases [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B07.


Label aggregation is an efficient and low cost way to make large datasets for supervised learning. It takes the noisy labels provided by non-experts and infers the unknown true labels. In this paper, we propose a novel label aggregation algorithm which includes a label aggregation neural network. The learning task in this paper is unsupervised. In order to train the neural network, we try to design a suitable guiding model to define the loss function. The optimization goal of our algorithm is to find the consensus between the predictions of the neural network and the guiding model. This algorithm is easy to optimize using mini-batch stochastic optimization methods. Since the choices of the neural network and the guiding model are very flexible, our label aggregation algorithm is easy to extend. According to the algorithm framework, we design two novel models to aggregate noisy labels. Experimental results show that our models achieve better results than state-of-the-art label aggregation methods.


In Mobile ad hoc networks (MANET), the quality of service (QoS) depends on the available resources in the network and node mobility, as mobility may result in frequent route failures. Some existing hybrid approach of collective-path routing technique rarely considers QoS metrics for path selection. In this paper, we propose a QoS enhanced hybrid collective-path routing protocol for MANET. In this protocol, topology discovery is performed proactively and route discovery is performed in the reactive manner. In proactive topology discovery phase, each node collects the battery power, queue length and residual bandwidth of every other nodes and stores in the topology information table (TIT). By exchanging the TIT among the nodes, th e topology is discovered. When the source node wants to forward the data packet to the destination, it utilizes the reactive route discovery technique where the multiple paths are established using collective- path Dijkstra algorithm. When any intermediate node does not recognize the next 2-hop information from TIT towards destination, the new collective-path route discovery is performed. By simulation results, it is shown that the proposed approach reduces the overhead.


This aim of this study is to examine the reasons for violence against teachers in Jordan from the perspective of high school students. The study followed a qualitative research approach by interviewing (50) students from grade twelve. Students were recruited in this study via the convenience sampling approach. The study revealed that teachers, school administration, school environment, media, and family conditions, were the major causes of student's violence against teachers. Teachers who experienced violence from students are the cause of this violence due to their actions and practices. Teachers are often exhausted, dispassionate, and overloaded with teaching and administrative duties. As a result, these duties sometimes hinder them not to communicate with students nicely or help students in solving their problems. Other times, students are violent against teachers because some teachers have low academic and educational performances. They are unable to offer counselling and psychological support to students from certain backgrounds. Subsequently, some students lack proper morals and discipline. School administrators are to be held responsible for the violence against teachers because they are unable to meet the students' needs.


Growth hormone (GH) together with cortisol are two important counter-regulatory hormones maintaining normal glycemia. Hyperinsulinemic hypoglycemia is a disorder of this counter-regulation described in neonates. We report here a rare case of reversible dissociated hypopituitarism secondary to an insulinoma in a 38-year-old man referred for investigation of hypoglycemic episodes. Hormonal investigations were in favour of dissociated anterior pituitary failure, with growth hormone and corticotroph deficiency. The hypothalamic-pituitary MRI was normal. The fasting test argued in favour of a hyperinsulinemic hypoglycemia. The abdominal scan and the endoscopic ultrasound showed a mass within the tail of the pancreas. Distal pancreatectomy was performed. Histology disclosed an insulinoma. On follow-up, no hypoglycemic episodes recurred and cortisol and GH response to induced hypoglycemia was normal. Our clinical case shows that hyperinsulinemia and hypoglycemia in patients with insulinoma can give rise to functional growth hormone and corticotrophin deficiency. The pathophysiological mechanism of this defective counter-regulation remains to be clarified; some studies suggest it could be related to hyperinsulinemia-induced decreased in CRF secretion and GHRH pulse.


This study aims to determine the effect of addition of blondo on the characteristics of brown rice flakes and determine the appropriate addition of blondo to get the best brown rice flakes characteristics. The design used in this study was Completely Randomized Design with the treatment of adding blondo consisting of 6 levels, namely 0%, 30%, 40%, 50%, 60% and 70%. This study was repeated three times to obtain 18 experimental units. The data obtained were analyzed by analysis of variance and if the treatment had a significant effect it was followed by DMRT (Duncan Multiple Range Test). The results showed that the addition of blondo had a significant effect on water content, protein content, fat content, carbohydrate content, crude fiber content, water absorption, aroma scoring test, taste scoring test and texture scoring test. Brown rice flakes with the addition of 40% blondo was the best treatment with characteristics water content 3.58%, ash content 1.62%, protein content 10.97%, fat content 13.76%, carbohydrate content 70.07%, crude fiber content 4.21%, water absorption 43.25%, and color rather liked, aroma rather typical coconut and rather liked, taste rather typical coconut and rather liked, texture crispy and rather liked and overall acceptance rather liked.


Isotope analysis has proved to be an extremely important tool in the traceability process; however, statistical analyses of the results show discrepancies, as the data depend on and originate from several chemical elements such as carbon, hydrogen, oxygen, nitrogen and sulfur (CHONS). In order to establish the proper analysis of traceability data for birds using the stable isotope technique and evaluate the need for a combined analysis of the variables, data for carbon-13 and nitrogen-15 were used from eggs (albumen + yolk) of laying hens and the pectoral muscle of broilers, which were subjected to univariate statistical analysis (ANOVA and complemented with Tukey's test) and multivariate statistical analysis (MANOVA and Discriminant Analysis). The data were analyzed using Minitab 16 software, and the results, corroborated in the theory, confirm the need for multivariate analysis, showing also that discriminant analysis clarifies questions from the results of the other analysis methods compared in this study.


This research investigated whether action semantic knowledge influences mental simulation during sentence comprehension. In Experiment 1, we confirmed that the words of face-related objects include the perceptual knowledge about the actions that bring the object to the face. In Experiment 2, we used an acceptability judgment task and a word-picture verification task to compare the perceptual information that is activated by the comprehension of sentences describing an action using face-related objects near the face (near-sentence) or far from the face (far-sentence). Results showed that participants took a longer time to judge the acceptability of the far-sentence than the near-sentence. Verification times were significantly faster when the actions in the pictures matched the action described in the sentences than when they were mismatched. These findings suggest that action semantic knowledge influences sentence processing, and that perceptual information corresponding to the content of the sentence is activated regardless of the action semantic knowledge at the end of the sentence processing.


Oil and gas pipeline operators routinely use magnetic flux leakage (MFL) and ultrasonic (UT) in-line inspection (ILI) to detect, locate and size metal losses caused by corrosion. As a preliminary step in fitness-for-service evaluations, the quality of the ILI is assessed through statistical comparison of the ILI data with data gathered in the field at dig sites. This work presents generalized criteria for the performance assessment and calibration of MFL and UT ILI tools from field measurements. The proposed criteria are capable of accounting for the measurement errors of both the ILI tool and the field instrument. The performance assessment of the ILI run is based on the determination of the minimum number of unsuccessful field verifications required to reject the ILI at a given significance level. The calibration of the ILI data uses new, simplified, error-in-variables methods to estimate the true size of the corrosion metal losses reported by the ILI tool. The proposed methodology also allows for determination of the errors associated with the estimation of the true defect depths. This information is of utmost importance in conducting reliability and risk assessments of pipelines based on either the probability distribution properties of the pipeline defect population, or the probability of failure of each individual defect in the pipeline. The proposed criteria are tested using Monte Carlo simulations and a real-life case study is presented to illustrate their application.


There has been an ongoing debate in the research literature on violations of trustworthiness and the effectiveness of various forms of repair. In this article, three studies compare the effectiveness of several variables hypothesized to repair perceived trustworthiness in a negotiation context: (a) the use of words (accounts or apologies) versus deeds (compensation for the costs of violation), separately and in combination; (b) whether words or deeds pointed to the past or to the future; (c) the effect of an active or passive third-party monitor of the negotiation, and (d) the type of trustworthiness (competence versus integrity) that was violated. Results show support for the repair effects for deeds over words, and that a focus on the past violation (through either words or deeds) is more effective than looking toward the future. Deeds, rather than words, also accounts for the strong impact of the combination of the two courses of action. In addition, results show that an active third-party intervention has a stronger impact on repair than a passive intervention. Implications for theory and practice are discussed along with suggestions for future research.


In this report, a preselection of alarms in a system for automated screening of cervical cancer based on depositing the cell sample linearly as a "cell trace" on a tape and analyzing it at different decision levels with increasing complexity, and preliminary results on analyzing cervical material with this system are discussed. The "cell trace" is analyzed with the slit-scan technique. Six parameters are computed: 1) cellular diameter; 2) nuclear diameter; 3) nuclear fluorescence (acriflavin-Feulgen) as nuclear DNA; 4) cellular fluorescence; 5) nuclear to cytoplasm ratio (N/C ratio); and 6) nuclear density. At present, only nuclear fluorescence is used to define a decision boundary between normal and potentially atypical cells. Under this criteria the slit-scan analysis leaves 5% of the events in a sample that must be rechecked at a second decision level in normal cell samples. A further reduction is expected when several slit-scan parameters are used at the first decision step. All events declared suspicious will be investigated in more detail by a two dimensional image analyzing system where the fluorescence image is generated by a laser scanning system. Results obtained in preliminary experiments are discussed in this paper.


In the area of targeted drug delivery, the colonic region of GI tract is the one that has been embraced by scientists and is being extensively investigated over the past two decades. Targeted delivery to the colon is being explored not only for local colonic pathologies, but also for systemic delivery of drugs like proteins and peptides. These are otherwise degraded and/or poorly absorbed in upper GIT but may be better absorbed from the more benign environment of the colon. The treatment of disorders of the large intestine (colon), such as Colon cancer, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) i.e. Ulcerative colitis and Crohn's disease, Diverticulitis and other colon diseases, where it is necessary to attain a high concentration of active agent, maybe efficiently achieved by colon specific delivery. This is also a potential site for the treatment of diseases sensitive to circadian rhythms such as asthma, angina, hypertension and arthritis. The primary approaches used to obtain colon specific delivery were based on prodrugs; pH dependent, time dependent systems or microflora activated systems has achieved limited success. However, recently continuous efforts have been taken on designing colon specific delivery systems with improved site specificity and versatile drug release kinetics to accomplish different therapeutic needs. Evaluation is performed by maintaining simulated condition using dissolution testing method closely mimic the in vivo colonic environment with regard to pH, the volume and distribution of fluids, bacteria, composition and activity of enzymes, and the mixing intensity, while being able to discriminate the impact of upper GI tract transit on the delivery system. The focus of this review is to provide detailed insight into the various colon diseases, approaches used to target the therapeutic agents specifically to the colon and evaluation parameters for colon specific drug delivery.In the area of targeted drug delivery, the colonic region of GI tract is the one that has been embraced by scientists and is being extensively investigated over the past two decades. Targeted delivery to the colon is being explored not only for local colonic pathologies, but also for systemic delivery of drugs like proteins and peptides. These are otherwise degraded and/or poorly absorbed in upper GIT but may be better absorbed from the more benign environment of the colon. The treatment of disorders of the large intestine (colon), such as Colon cancer, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) i.e. Ulcerative colitis and Crohn's disease, Diverticulitis and other colon diseases, where it is necessary to attain a high concentration of active agent, maybe efficiently achieved by colon specific delivery. This is also a potential site for the treatment of diseases sensitive to circadian rhythms such as asthma, angina, hypertension and arthritis. The primary approaches used to obtain colon specific delivery were based on prodrugs; pH dependent, time dependent systems or microflora activated systems has achieved limited success. However, recently continuous efforts have been taken on designing colon specific delivery systems with improved site specificity and versatile drug release kinetics to accomplish different therapeutic needs. Evaluation is performed by maintaining simulated condition using dissolution testing method closely mimic the in vivo colonic environment with regard to pH, the volume and distribution of fluids, bacteria, composition and activity of enzymes, and the mixing intensity, while being able to discriminate the impact of upper GI tract transit on the delivery system. The focus of this review is to provide detailed insight into the various colon diseases, approaches used to target the therapeutic agents specifically to the colon and evaluation parameters for colon specific drug delivery. Keywords Inflammatory bowel disease, pH dependent, Prodrug, Circadian rhythms, Colon specific drug delivery.


London—The British government has just completed a massive peer review of the country's university departments and research institutes, grading them on the quality of their faculty members. Some universities tried to improve their ratings by withholding some faculty members from the review. At stake: $1.1 billion in infrastructure funding that will be distributed in part on the results of the reviews.


Ziziphus (Rhamnaceae) is a widely distributed genus across the Australasian and African tropics with unusual diversity in habit, and many species of significance to people. Here, we quantify the environmental limits of Ziziphus species and examine inter‐specific relationships among functional traits, environment, biome, and range size. We developed a curated geolocation database for Ziziphus and used it to examine the environmental limits of the genus relative to temperature, rainfall, and seasonality. To assess the relationship between biome and habit, permutational analysis of variance was used, while hierarchical clustering was used to determine whether habit, leaves, and fruit traits were related to biome. For 40 species with adequate geolocation data, range size was calculated to assess its relationship with habit, biomes, and cultivation. Finally, niche identity tests were used to determine niche equivalency among cultivated and non‐cultivated species. Liana species are restricted to closed forests and the geoxylic habit is found only in open grasslands. Further, habit is significantly associated with range size, with trees having on average larger range sizes than shrubs, lianas, and geoxyles, but biome was not correlated with range size. Cultivated species have ranges ~10 times that of non‐cultivated tree species and with significantly different and broader environmental niches. The unusually wide distribution of Ziziphus can be explained by its diversity of habits associated with different biomes spanning continents. This, along with the usage of many Ziziphus species by people for their fruits, expands the range and environmental occupation of the genus.


Naturally occurring food/feed contaminants have become a significant global issue due to animal and human health implications. Despite risk assessments and legislation setpoints on the mycotoxins' levels, exposure to lower amounts occurs, and it might affect cell homeostasis. However, the inflammatory consequences of this possible everyday exposure to toxins on the vascular microenvironment and arterial dysfunction are unexplored in detail. Circulation is the most accessible path for food-borne toxins, and the consequent metabolic and immune shifts affect systemic health, both on vascular apparatus and bone homeostasis. Their oxidative nature makes mycotoxins a plausible underlying source of low-level toxicity in the bone marrow microenvironment and arterial dysfunction. Mycotoxins could also influence the function of cardiomyocytes with possible injury to the heart. Co-occurrence of mycotoxins can modulate the metabolic pathways favoring osteoblast dysfunction and bone health losses. This review provides a novel insight into understanding the complex events of coexposure to mixed (low levels) mycotoxicosis and subsequent metabolic/immune disruptions contributing to chronic alterations in circulation.


ABSTRACT Al2O3/glass/hBN composites were successfully fabricated for the LTCC applications. Alignment and homogeneous distribution of the platelet hBN particles during tape casting allowed high hBN (5 wt%) loading as well as facilitated densification at 800°C (density of 2.65 g/cm3, apparent porosity of 0.7%). XRD results proved that hBN neither chemically reacted with the other phases nor decomposed with temperature, which was critical to increase thermal conductivity and at the same time to decrease dielectric constant. Dielectric constant of the dense composites decreased (or, alternatively, enhanced) with increasing hBN content from 7.3 for the 0 wt% hBN to 6.55 for the 5 wt% hBN at 5 MHz. In addition, hBN addition strongly improved the mean thermal conductivity from 1.86 W/m·K for the 0 wt% hBN to 2.43 W/m·K for the 5 wt% hBN between 75°C and 250°C. Therefore, the hBN phase itself effectively optimized both dielectric and thermal properties at the same time and made the Al2O3/glass/hBN composites a promising candidate for the LTCC applications.


The paper discusses the threats and opportunities of a platform developed at Anhembi Morumbi University (Sao Paulo, Brazil), named Tubarão (Shark), which generates open communication among students, professors, university staff and the high administration. It was planned as an orkut-like environment, with the intent that the students would quickly and easily accept and adopt it as an online tool. The paper investigates the vision of the system, the history of its implementation, and the current testing phase, previewing its potential problems as well as its breakthrough applications, including distance learning. It also presents a monitoring research of the platform during two months, analyzing data as the growth of the number of communities, number of users, number of files deposited at the system, and the number of posts, as well as the major subjects of interest, selecting specific threads of interesting conversations established by the different levels of members at the institution.


An auditory selective attention set allows one to enhance the processing of goal-relevant sound events, which is reflected by the enhancement of the N1 event-related potential (ERP). The present study investigated whether the sensory consequences of distraction (i.e., involuntary attention changes triggered by infrequent sensory events) can be revealed as the removal of this attentional ERP enhancement. Continuous tones featuring occasional gaps were presented, and participants performed a gap-detection task. Independently from gaps, abrupt pitch changes (glides) were introduced, either rarely or frequently, in separate conditions. Whereas rare glides preceding gaps by 150 ms strongly impacted gap-detection performance and gap-related N1 amplitudes, their impact on gaps following rare glides by 650 ms was significantly smaller in both measures. This result demonstrates the utility of N1 in probing the sensory impact of auditory distraction.


The velocity and the height at the surface of a dynamic ice sheet are observed. The ice sheets are modeled by the full Stokes, SIA and SSA equations. The sensitivity of the observed quantities at the ice surface to parameters in the models, e.g. the base topography and friction coefficients, is analyzed by first deriving the time dependent adjoint equations. Using the adjoint solutions, the effect of a perturbation in a parameter is obtained. The adjoint equations are solved analytically and numerically and the sensitivity is determined in several examples in two dimensions.


4D flow MRI provides comprehensive assessment of cardiovascular hemodynamics. However, the current clinical usage of standard 4D flow MRI is hindered by long scan times and extensive, time-consuming post-processing such as eddy current corrections, noise masking, and 3D vessel segmentation. We seek to address this by developing a fully automated image reconstruction and post-processing pipeline for highly-accelerated aortic 4D flow MRI (R=5.7-10.2). The fully automated pipeline was shown to provide good-to-excellent agreement in quantitative and hemodynamic measures to conventional 4D flow MRI (GRAPPA, R=2) with manual post-processing. Additionally, the pipeline only requires <10 minutes compared to 20 minutes manually.


The effectiveness and feasibility of the three biochar materials for remediation of arsenic (As) and lead (Pb) contaminated soil were explored in this study. Significant reduction of bioaccessibility and migration risks of both heavy metals have been explained mechanistically by incubation, column experiments and numerical simulation. Langmuir equation fitted As and Pb sorption isotherms better in the control and biochar (BC) amended soils, while Freundlich model was more suitable for iron modified biochar (Fe-BC) and sulfur/iron modified biochar (S/Fe-BC) amended soils, indicating that modified biochar promoted chemical adsorption process for As and Pb. For the three biochar materials, S/Fe-BC showed the best effects on reducing the bioavailability of As and Pb, with a decrease of 40.42%-64.21%. The reduction in bioaccessibility by metal portioning into available and non-available fractions was better for illustrating the mechanisms including adsorption, precipitation/coprecipitation and As(III) oxidation behind S/Fe-BC efficacy. Moreover, S/Fe-BC can effectively inhibit the leaching behavior of As and Pb under acid rain, which increased by 99.89% and 90.18%, respectively, compared with the control. The HYDRUS-1D modeling indicated that S/Fe-BC could continuously treat As (100 mg/L) and Pb (1000 mg/L) contaminated water for 16.22 years and 40.86 years, respectively, and ensure the groundwater quality criteria being met. Based on these insights, we believe that our study will provide meaningful information about the potentials of biochar derived materials for soil heavy metals' remediation.


The paper considers issues pertaining to creation of a model for controlling road traffic with the purpose to minimize delays on street and road network, which is proposed as an innovative one while developing an intelligent transport system of the large city that is Minsk. The developed model has a complex structure of algorithmic support. The first-level model has been implemented on the basis of fuzzy logic, for which a program has been developed and conditions have been determined, and operation of traffic light at a real local intersection of Minsk, which is included in the automated traffic management system, has been simulated. Innovation in the first-level model is an approach in determining conditions while detecting a fuzzy set without using a standard algorithm that is an algorithm of local flexible regulation. The paper proposes and investigates a model that works on the basis of operationally obtained parameters of traffic flow intensity at characteristic points (sections) of street and road network. Efficiency of the first-level model has been equal to 8 % due to optimization of a traffic light cycle (reduction of transport delays during passage of stop lines). Results of the simulation using the proposed computer program have made it possible to improve efficiency of traffic management on the studied highway (Logoysky trakt) in Minsk city of Minsk by 15 % due to decrease of delay level in case of unilateral coordination. The algorithm has been already implemented as part of the current automated traffic management system in the city of Minsk and it has shown its efficiency. However this efficiency can be increased if it is used together with an algorithm for searching maximum volume of motion in a cycle with a distributed intensity pulse. It has been planned to take into account this specific feature when increasing possibilities for algorithmization of traffic management.


Ischemic heart disease is the leading cause of death and disability worldwide. Reperfusion causes additional injury beyond ischemia. Endothelial cells (ECs) can protect cardiomyocytes (CMs) from reperfusion injury through cell-cell interactions. Co-cultures can help investigate the role of cell-cell interactions. A mixed co-culture is the simplest approach but is limited as isolated treatments and downstream analyses of single cell types are not feasible. To investigate whether ECs can dose-dependently attenuate CM cell damage and whether this protection can be further optimized by varying the contact distance between the two cell lines, we used Mouse Primary Coronary Artery Endothelial Cells and Adult Mouse Cardiomyocytes to test three types of cell culture inserts which varied in their inter-cell layer distance at 0.5, 1.0, and 2.0 mm, respectively. In CMs-only, cellular injury as assessed by lactate dehydrogenase (LDH) release increased significantly during hypoxia and further upon reoxygenation when the distance was 2.0 mm compared to 0.5 and 1.0 mm. When ECs and CMs were in nearly direct contact (0.5 mm), there was only a mild attenuation of the reoxygenation injury of CMs following hypoxia. This attenuation was significantly increased when the spatial distance was 1.0 mm. With 2.0 mm distance, ECs attenuated CM injury during both hypoxia and hypoxia/reoxygenation, indicating that sufficient culture distancing is necessary for ECs to crosstalk with CMs, so that secreted signal molecules can circulate and fully stimulate protective pathways. Our findings suggest, for the first time, that optimizing the EC/CM co-culture spatial environment is necessary to provide a favorable in vitro model for testing the role of ECs in CM-protection against simulated ischemia/reperfusion injury. The goal of this report is to provide a step-by-step approach for investigators to use this important model to their advantage.


In the study of cochlear function an animal model in which apical outer hair cells could be destroyed with retention of inner hair cells would be valuable. Our object was to attempt to reproduce a reported method in a scientific manner. Behavioural response thresholds to pure tones were recorded in 7 monaural chinchillas. In 5, Kanamycin was administered in ototoxic dosage until the thresholds deteriorated. The other 2 served as controls. Cochlear histology was assessed from embedded surface preparations. In only one of the 5 animals was the aim achieved. In this animal outer hair cells were absent virtually throughout the cochlea and inner hair cell retention was basal. Ths thresholds were elevated on average 40 dB throughout the frequency range. This is in keeping with current concepts of cochlear function.


The main stages of endoscopic skull base repair in patients with cerebrospinal fluid (CSF) leakage are identification of bone boundaries of the fistula and its closure by auto- and allografts. Fibrin glue can be used to fix plastic materials and additionally seal skull base defect.

OBJECTIVE
To analyze efficacy and safety of Vivostat autologous fibrin glue for endoscopic skull base repair in patients with nasal CSF leakage and to compare postoperative outcomes after defect closure by Vivostat fibrin glue and allogeneic fibrin glue.

MATERIAL AND METHODS
A retro- and prospective analysis included 56 patients with nasal CSF leakage who were treated at the Burdenko Neurosurgery Center between January 2021 and June 2022. Patients were divided into 2 groups: Vivostat fibrin glue (n=27, 48.2%) and allogeneic fibrin glue (n=29, 51.8%). Demographic and clinical perioperative data were analyzed.

RESULTS
No early postoperative recurrence of CSF leakage was registered in both groups, whereas meningitis occurred in 2 cases in each group. Recurrent CSF leakage in delayed postoperative period occurred in 1 patient (3.4%) of the control group (p>0.05). Incidence of perioperative complications, subfebrile temperature in early postoperative period, surgery time and hospital-stay were similar.

CONCLUSION
Vivostat autologous fibrin glue is a safe and effective method for fixing the grafts in endoscopic skull base repair. The advantages of this approach are easy application, elimination of the risk of allergic, immunological and infectious complications, as well as acceleration of tissue regeneration.


This article traces Foucault's distinctive commitment to 'post-structuralism' through tracing the affinities and departures from structuralism. It is argued that under the infuence of Nietzsche, Foucault's approach marks a distinct break with structuralism in several crucial respects. What results is a materialist post-structuralism which is also distinctively different from the post-structuralism of writers such as Derrida, Lyotard and Baudrilliard. Foucault's account of neo-liberalism as an historically formed discourse is presented as an example of materialist post-structuralist analysis.


Summary form only given. An automated biomechatronic small fluid sample preparation system for DNA processing has been developed in the Genomation Laboratory at Department of Electrical Engineering of the University of Washington. The system automates steps necessary to prepare DNA for sequencing using sample volumes ten times smaller than the current state of the art manual and automated instrumentation. This will significantly reduce the time and cost of DNA sequencing and will help the Human Genome Project meet its goal of determining all three billion bases of human DNA sequence by the year 2005. The biomechatronic system comprising electromagnetic actuators, piezoceramic actuators, pneumatic pumps, linear mechanisms, thermal controllers, optical sensors, electronics, computer control and software is described in detail. Successful experimental results including restriction enzyme digests and polymerase chain reactions performed with this novel system are presented.


Determining the parametrization of the curve is a fundamental problem in approximation and interpolation. The goal of this paper is to develop an accurate and robust algorithm for the minimum zone problems. In this paper, we use an interval bias adaptive linear neural network structure together with an appropriate cost function and the least mean squares learning algorithm to carry out the interval regression analysis. Through appropriate choice of the output function of the input neuron, the interval polynomial regression use of a neural network (IPRNN) method developed in this paper is applicable to many problems (interval algebraic polynomial approximation, evaluation of straightness, roundness and ellipticity and so on). Generally, these problems have complicated constraints and the LSQ method cannot be used.


The drift motion of a freely floating deformable ice sheet in shallow water subjected to incident nonlinear waves and uniform current is studied by use of the Green–Naghdi theory for the fluid motion and the thin plate theory for an elastic sheet. The nonlinear wave- and current-induced forces are obtained by integrating the hydrodynamic pressure around the body. The oscillations and translational motion of the sheet are then determined by substituting the flow-induced forces into the equation of motion of the body. The resulting governing equations, boundary and matching conditions are solved in two dimensions with a finite difference technique. The surge and drift motions of the sheet are analysed in a broad range of body parameters and various wave-current conditions. It is demonstrated that wavelength to sheet length ratio plays an important role in the drift response of the floating sheet, while the sheet mass and rigidity have comparatively less impact. It is also observed that while the presence of the ambient current changes the drift speed significantly (almost linearly), it has little to no effect on its oscillations. However, under the same ambient current, the drift speed changes remarkably by the wave period (or wavelength).


Security and safety are key topics of concern in the globalized and interconnected world. While the terms "safety" and "security" are often used interchangeably in everyday life, in academia, security is mostly studied in the social sciences, while safety is predominantly studied in the natural sciences, engineering, and medicine. However, developments and incidents that negatively affect society increasingly contain both safety and security aspects. Therefore, an integrated perspective on security and safety is beneficial. Such a perspective studies hazardous and harmful events and phenomena in the full breadth of their complexity—including the cause of the event, the target that is harmed, and whether the harm is direct or indirect. This leads to a richer understanding of the nature of incidents and the effects they may have on individuals, collectives, societies, nation-states, and the world at large.


AINEIOT nOAIOPKHTIKA (Aeneas on Siegecraft.) A critical edition prepared by L. W. HUNTER, revised with some additions by S. A. HANDFORD. Pp. lxxxii + 266. Oxford : Clarendon Press, 1927. 18s. THIS edition of Aeneas, with translation, was prepared before the war by the late Mr. L. W. Hunter, who was killed on the Somme. It has now been revised, with many additions, by Mr. S. A. Handford, who has also revised the text in the light of Schoene's edition; Professor Gilbert Murray contributes an appreciative notice of the author. It is much fuller than the recent Loeb edition, good as that was, for it contains 82 pages of introduction and 138 of commentary; the translation where I have tested it seems excellent and reads fluently, and the commentary gives a mass of information, with occasional diagrams; in particular, the explanation of the shelter for sappers (XXXVII. 9) is both new and convincing. The commentary is rather self-denying over matters of illustration later than Aeneas—it seems strange to find towers and 'tortoises' treated without allusion to Demetrius' machines; but the only actual lapses I have noticed are on p. 238—the coins show that Datames did take Sinope—and on pp. 143 -4, where Mithridates I. of Pontus gets transferred to the fourth century and Lysimachus is treated very strangely. In the text of XXXI. 31, Casaubon's meaningless Atovv<no<s /cakos is unfortunately retained in preference to Schoene's brilliant and certain AcoX.09. But the principal merit of this book is philological, its treatment of Aeneas' language as ajstage in the development of the KOIVTJ; this is done at length and very thoroughly, and deserves much praise. (May I add two notes ? P. lx., 7roXtrapxps—there are numerous mentions of politarchs in second-century Macedonian and Thessalian inscriptions; and p. 146, e<f>eSpoi—Polyb. V. 34. 8 gives a good instance of i<peSpevco in Aeneas' sense.) For this purpose Aeneas date is important, and here the authors have made the mistake of treating the (temporary) cessation of the Locrian maiden-tribute in 346 as a terminus post quern non ; for Wilhelm has shown that this tribute revived, and existed in the third century (Jahresh. XIV., "1911, pp. 163, 186). However, Aeneas' approximate date is reasonably certain, and a strong case is here made for his identification with Aeneas of Stymphalus. English readers are now well off as regards Aeneas, who is important for fourth-century conditions, even if his one famous saying, iroppwffev KarahrjKos fiaXkovaa yvvtj, is fast ceasing to be true.


The evolution of heterodonty, the possession of varied tooth morphologies on the jaws of animals, has been relatively unexplored in ray‐finned fishes compared to terrestrial vertebrates, and to an even lesser degree in deep‐sea fish lineages. Lanternfishes (Myctophiformes) are an abundant and species‐rich group endemic to deep‐sea pelagic habitats. In this study, we document the presence of heterodonty on the oral jaws of lanternfishes, identifying differing anatomical and positional variations of dentition. We survey the anatomical variation in tooth morphology on the oral jaws of 114 lanternfish species across 37 genera and integrate our findings with a hypothesis of evolutionary relationships of lanternfishes to infer the number of times heterodonty evolved in this lineage. Our results indicate that heterodonty evolved at least six separate times on the oral jaws of lanternfishes, occurring as variable tooth morphologies in combination with villiform teeth. These combinations of tooth types include villiform plus hooked teeth, villiform plus hooked and recurved teeth, villiform plus spade, tricuspid, and hooked teeth, and villiform plus caniniform teeth. The reoccurring evolution of hooked teeth on the premaxilla and dentary in lanternfishes suggests heterodonty may serve an important functional role in their pelagic deep‐sea environment. Hooked teeth could aid in securing and retaining prey in the oral cavity and allow for species to specialize on differing food resources, vital attributes for organisms living in open‐ocean habitats.


This research examines the mobile-government services adoption, by combining both UTAUT and GAM models with adding new constructs for explaining the key factors that affect on adoption of mobile-government services. As a result, the study identified the critical factors that influence users' to adopt the system, and developed an integrated model as a powerful tool that assists in the adoption process of mobile-government applications. The novelty of this research will be an added value to the body of knowledge and its implications will be vital for researchers and decision/policy makers who are willing to make a change.


Aim The article outlines, at the level of political discourse, changes in drug and criminal policy that may have influenced the penal system as a backdrop to the rise of prison-based drug treatment programmes (PBDT) in Finland. Methods and Data Our perspective is historical. The article is based on historical and political documents, scholarly research and white papers. Results The history of PBDT in Finland is characterised by an absence of drug treatment programmes until the 1980s, first initiatives at the end of the 1980s, enthusiastic programme development from the mid-1990s, and decreasing interest during recent years. Unlike the National Drug Strategy, the Prison Drug Strategy aimed at a drug-free environment (zero tolerance) and implemented harm-reduction measures only to a limited extent. Conclusion The development of PBDT represents the new way of performing treatment in prisons, with features of managerialism. PBDT is also affected by an organisational segregation of rehabilitation and medical treatment, which prevents integration of harm-reduction measures with rehabilitative treatment, and is in conflict with general aims of integrating substance abuse treatment to mental and healthcare services in Finland. In the spirit of a new kind of Penal Welfarism, the role of documented individual risk and needs assessment in defining an offender's sentence has increased.


Convection and segregation in granular systems not only provide a rich phenomenology of scientifically interesting behaviours but are also crucial to numerous 'real-world' processes ranging from important and widely used industrial procedures to potentially cataclysmic geophysical phenomena. Simple, small-scale experimental or simulated test systems are often employed by researchers in order to gain an understanding of the fundamental physics underlying the behaviours of granular media. Such systems have been the subject of extensive research over several decades, with numerous system geometries and manners of producing excitation explored. Energy is commonly provided to granular assemblies through the application of vibration—the simplicity of the dynamical systems produced and the high degree of control afforded over their behaviour make vibrated granular beds a valuable canonical system by which to explore a diverse range of phenomena. Although a wide variety of vibrated systems have been explored in the existing literature, the vast majority are exposed to vibration along only a single spatial direction. In this paper, we study highly fluidised systems subjected to strong, multi-directional driving, providing a first insight into the dynamics and behaviours of these systems which may potentially hold valuable new information relevant to important industrial and natural processes. With a particular focus on the processes of convection and segregation, we analyse the various states and phase transitions exhibited by our system, detailing a number of previously unobserved dynamical phenomena and system states.


The optical diameter of the surface snow grains impacts the amount of energy absorbed by the surface and therefore the onset and magnitude of surface melt. Snow grains respond to surface heating through grain metamorphism and growth. During melt, liquid water between the grains markedly increases the optical grain size, as wet snow grain clusters are optically equivalent to large grains. We present daily surface snow grain optical diameters (dopt) retrieved from the Greenland ice sheet at 1 km resolution for 2017–2019 using observations from Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A. The retrieved dopt are evaluated against 3 years of in situ measurements in Northeast Greenland. We show that higher dopt are indicative of surface melt as calculated from meteorological measurements at four PROMICE automatic weather stations. We deduce a threshold value of 0.64 mm in dopt allowing categorization of the days either as melting or nonmelting. We apply this simple melt detection technique in Northeast Greenland and compare the derived melting areas with the conventional passive microwave MEaSUREs melt flag for June 2019. The two flags show generally consistent evolution of the melt extent although we highlight areas where large grain diameters are strong indicators of melt but are missed by the MEaSUREs melt flag. While spatial resolution of the optical grain diameter-based melt flag is higher than passive microwave, it is hampered by clouds. Our retrieval remains suitable to study melt at a local to regional scales and could be in the future combined with passive microwave melt flags for increased coverage.


T H E 'TALL OF ROME" in AD. 410 when Alaric and the Visigoths sacked the city to the u t t e r dismay and shock of Romans everywhere in the "civilized" world is seen by Pelikan as a historical paradigm by which other historical developments down through the centuries have been illuminated. Adam Smith's Wealth of Nations, Alexis de Tocqueville's analysis of American civilization, Edmund Burke's Reflections on the Revolution in France, and Oswald Spengler's Decline of the West are but a few illustrations of the abiding paradigm. Most notable of all, however, is Edward Gibbon's famous History of the Decline and Fall of the Roman Empire, which Pelikan analyzes in a very evenhanded manner at some length. It is well known that Gibbon had no love for Christianity and attributed the destruction of Roman civilization to Goths and Christians ("barbarism" and "religion"), not always taking very great pains to distinguish between the two. Pelikan endeavors to read Gibbon's history from within the latter's own mindset as he assessed the contributions of law, language, and religion which the declining Roman Empire left as its legacy to posterity. In order to achieve this, Pelikan analyzes Gibbon's interpretation of such contemporary Christian writings as Augustine's The City of God and Jerome's Letters and Commentary on Ezekiel. Out of the apocalyptic vision of Jerome's admonition ("The Roman world is falling, and yet we are holding up our heads instead of bowing them down!") and Augustine's beatific embrace of the eschatological "City of God" came "the excellent empire" that Gibbon grudgingly praised in the words: "If the decline of the Roman Empire was hastened by the conversion of Constantine, his victorious religion broke the violence of the fall, and mollified the ferocious temper of the conquerors."


Simulation, emulation, and wide-area testbeds exhibit different tradeoffs with respect to fidelity, scalability, and manageability. Network security and network planning/dimensioning experiments introduce additional requirements compared to traditional networking and distributed system experiments. For example, high capacity attack or multimedia flows can push packet forwarding devices to the limit and expose unexpected behaviors. Many popular simulation and emulation tools use high-level models of forwarding behavior in switches and routers, and give little guidance on setting model parameters such as buffer sizes. Thus, a myriad of papers report results that are highly sensitive to the forwarding model or buffer size used.
In this work, we first motivate the need for better models by performing an extensive comparison between simulation and emulation environments for the same Denial of Service (DoS) attack experiment. Our results reveal that there are drastic differences between emulated and simulated results and between various emulation testbeds. We then argue that measurement-based models for routers and other forwarding devices are crucial. We devise such a model and validate it with measurements from three types of Cisco routers and one Juniper router, under varying traffic conditions. The structure of our model is device-independent, but requires device-specific parameters. The compactness of the parameter tables and simplicity of the model make it versatile for high-fidelity simulations that preserve simulation scalability. We construct a black box profiler to infer parameter tables within a few hours. Our results indicate that our model can approximate different types of routers. Additionally, the results indicate that queue characteristics vary dramatically among the devices we measure, and that backplane contention must be modeled.


Primary malignant sarcomas of the spine are extremely rare. Because of biological heterogeneity, these tumors have variable sensitivity to radiation and chemotherapy. Adequate local control through complete tumor removal is an important therapeutic goal. However, aggressive resection of tumors in the spinal column must be coupled with restoration of spinal column stability and minimization of neural deficits. The balance of these factors makes treatment of primary sarcomas of the spine challenging, and dictates an individual approach to treatment. We report on a 18 years old man with primary Ewing's sarcoma of the nonsacral spine. The clinical picture and imaging characteristics were analyzed as well as the management modalities and outcome.


Basic operational characteristics of the plasma focus are considered from design perspectives to develop powerful radiation sources. Using these ideas we have developed two compact plasma focus (CPF) devices operating in neon with high performance and high repetition rate capacity for use as an intense soft X-ray (SXR) source for microelectronics lithography. The NX1 is a four-module system with a peak current of 320 kA when the capacitor bank (7.8 /spl mu/F/spl times/4) is charged to 14 kV. It produces 100 J of SXR per shot (4% wall plug efficiency) giving at 3 Hz, 300 W of average SXR power into 4/spl pi/. The NX2 is also a four-module system. Each module uses a rail gap switching 12 capacitors each with a capacity of 0.6 /spl mu/F. The NX2 operates with peak currents of 400 kA at 11.5 kV into water-cooled electrodes at repetition rates up to 16 Hz to produce 300 W SXR in burst durations of several minutes. SXR lithographs are taken from both machines to demonstrate that sufficient SXR flux is generated for an exposure with only 300 shots. In addition, flash electron lithographs are also obtained requiring only ten shots per exposure. Such high performance compact machines may be improved to yield over 1 kW of SXR, enabling sufficient exposure throughput to be of interest to the wafer industry. In deuterium the neutron yield could be over 10/sup 10/ neutrons per second over prolonged bursts of minutes.


In the egg shells of Rhea sp. there are grooves on the surface and it is into these grooves that one or more pore mouths open.

Five egg shells of Rhea americana and four of Rhea darwinii were studied in detail in respect of the numbers of pore mouths and the number, length and orientation of the grooves. It was found that R. americana had nearly twice as many pore mouths and grooves as had R. darwinii. Their distribution in both species showed more and longer grooves and more pore mouths in the equatorial regions than in the polar regions of the shell. The grooves were also found to be approximately longitudinally orientated in the equatorial regions but this orientation became less marked towards the polar regions. Not surprisingly longer grooves tended to have more pore mouths than did shorter grooves, but, in addition, broader grooves were associated with greater length too.


approved Frank S. Conklin Agricultural production in the Sahelian region of Africa is among the lowest in the world. Cyclical infestations of locusts and grasshoppers have contributed to this low productivity. The infestations appear to be triggered by heavy rainfall at the beginning of a crop season after extended drought. Because locusts and grasshoppers are migratory, their control on a local and farm by farm basis is difficult. To combat the problem of periodic outbreaks USAID has provided direct assistance through aerial spraying of grasshoppers in a number of African countries.' This includes a control program in the north African country of Chad in 1987. From the beginning concern arose as to when it is economically desirable to control grasshoppers. The International Plant Protection Center (IPPC) at Oregon State University was awarded a contract for economic evaluation of spraying in Chad which included development of a grasshopper crop loss simulation model (GHLSIM) driven by climatic factors for grasshopper and crop growth. GHLSIM's posterior analysis of the 1987 anti-grasshopper campaign produced results with a wide range of B/C ratios across the 13 Redacted for Privacy sites which were evaluated. The B/C ratios ranged from 0 to 6.9. To test GHLSIM's use beyond weather conditions of a single year (1987), a Monte Carlo simulation technique was used to generate long term (100 year) rainfall patterns at selected sites and a series of expected benefits generated. The effect of rainfall variability upon economic benefits was assessed. So also were changes in grasshopper population densities and output prices. Results are presented graphically under a number of such conditions to understand the biophysical relationships among grasshoppers, crop, natural vegetation and rainfall as modeled by GHLSIM. The model is sensitive to within season and to some extent between season weather variation. Rainfall appears to be the dominant variable controlling crop production, regardless of grasshopper densities. When weather is the overriding factor, changes in grasshopper density levels do not play a dominant role in affecting B/C ratios. When weather is not a constraint for crop production, grasshopper density changes can affect benefits significantly. In its present form the GHLSIM model cannot be used as an early warning indicator. While the model appears to predict crop production quite well, model refinement which will change the qualitative prediction of grasshopper populations to a quantitative one throughout a crop season is still needed. When this is completed and both the GHLCROPS and GHLOSE submodels performance are validated against field observations, the GHLSIM model can be used as an early warning predictor. With these accomplishments GHLSIM can then be considered for use in the public policy arena for assessing what areas to spray, when and what distributional effects may be involved. Effect of Weather Variation on Economic Results From Grasshopper Control Tactics in Chad: A Partial Validation of GHLSIM


This article captures some social aspects of a marginalized area of Galati: The Valea Oraşului neighborhood. In the past this area was developed, here lived many merchants who thrived through their businesses. The communist era transformed this historical area into an industrial center, but after the Revolution of December 1989, by ceasing its industrial activity, the Valea Oraşului district, it turned into a peripheral area both by the lack of development initiatives and by moving a large, marginalized population of Roma ethnicity.


Financial market is institutionally represented by the financial system. The segments of the decentralized financial system correspond to the sectors of the financial market. Financial relations are formed outside the financial market - in the form of a public financial system. The structure of the decentralized financial system is the relationship between the banking sector and liquid securities markets. The financial structure as a source of ways and mechanisms of economic development is the subject of discussions. In recent years, there has been an increase in the convergence of sectors of the financial system. The financial structure continues to transform. The principles of regulation are the main basic on which the practical actions of the state to regulate the securities market should be based. In contrast to state regulation of the market as a whole, that is, regulation of macroeconomic processes, regulation of the securities market is predominantly administrative in nature. The article expresses an opinion on the expediency of restoring the fundamental entry in the Law of Georgia "On the Securities Market", according to which trading in government securities is allowed only on the stock exchange; The need to protect the interests of minority investors, greater transparency of information about issuers, regulated participants, large investors is also emphasized. The market regulation system is formed under the influence of problems that accumulate and require solutions. The regulation of the securities market by the state is explained by the role played by this market and the desire to increase the reliability of the market and the level of confidence on the part of all its participants. Regulation of the stock market by the state will be supplemented by regulation by self-regulatory participants. Public regulation (regulation through public opinion) is also very important. The reaction of the population to any action on the securities market is the primary reason for initiating this or that regulatory action on the part of the state or market professionals. The development of the securities market in Georgia will be facilitated by a deeper discussion of the mentioned market problems and ways to overcome them. The article highlights the modern trend of creating stock groups in the securities market; The impact of the Covid pandemic on the stock markets is shown; The different situation in the world is analyzed in terms of creating a system of financial market regulation. Currently, the banking system is the dominant sector of the financial market in Georgia, which has been determined by the policy of the National Bank of Georgia for a long period of time. It is no so important which body should play the role of a regulator - the NSC or the National Bank - the determining factors are the will of the (financial) authorities, the methodology of supervision and the qualifications of the staff. Keywords: securities market, principles of regulation, Regulatory system, IOSCO. JEL Codes: L26, L32, M14


Charting out the history of the study of African responses to imperialism, crises and underdevelopment in Africa, African Socialism as an Ideology for development was found course social and political) crises. The ideology, which was muted and practiced some decades ago and currently being canvassed through other guises by some African leaders as a panacea for myriads of African retested for its validity in this study. The findings however showed incapacity of the ideology in resolving African underdevelopment crisis. This study attempts to contextualize and situate this failure to the historical experiences, the implications of the experiences and their relationships to deepening contradictions, conflicts and crises. The resurgence of coups d'état, civil wars interstate wars, terrorism and other forms of prote in Africa as well as the visible insecurity of the dominant forces attest very clearly to the dimensions of the Africa's crisis. To escape from the present crisis, Africa has to embark on a radical break from her colonial past f structures that would guarantee democratization and sustainable development that is domesticated in the continent's history.


Debates about the original meaning of the First Amendment's establishment clause have typically featured opposition between "separationists" and "accommodationists" of various shapes and sizes, but an altogether different interpretation holds that the establishment clause was not intended to constitutionalize any substantive principle of religious freedom at all: rather it was simply intended to affirm that religion would remain within the jurisdiction of the states (where virtually everyone at the time assumed it was and should be) and would not be placed within the jurisdiction of the new national government. In recent years, this jurisdictional interpretation has gained the support (in one or another version) of scholars including Akhil Amar and Philip Hamburger and of Justice Clarence Thomas, but it has been criticized by other scholars including Kent Greenawalt, Douglas Laycock, and Noah Feldman. This article carefully reviews the arguments and evidence, pro and con, and concludes that the jurisdictional interpretation provides the most persuasive account of the original meaning of the establishment clause. At least some of the objections from Greenawalt, Laycock and others reflect an assumed dichotomy between "jurisdictional" and "substantive" constitutional provisions. This article criticizes that assumption and reflects on what it means for a constitutional provision such as the establishment clause to be "purely jurisdictional" in nature.


Matrix-matched reference materials are important for in situ trace and isotope analyses. In this study, we developed an efficient method for preparing chemically homogeneous magnetite (MtTR-1) without adding a binder. The initial magnetite powder (d90 = ~80 μm) was milled to form micron (d90 = 3.0 μm) particles in an anhydrous ethanol suspension and argon environment using a high-energy vibration ball mill. The obtained particles were pressed into a magnetite cylinder (10 mm in diameter and 9.2 mm in height), sealed into a silver tube, and sintered at 500 C and 1.2 GPa for 2 h. Laser Raman spectroscopy results indicated that high-temperature and high-pressure sintering did not induce any phase transformation. The smooth surface after polishing was subjected to repeated analyses via electron probe microanalyzer using a spot size of 5 μm and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) using spot sizes of 3860 μm. The results indicated that the texture and chemical composition are homogeneous in MtTR-1. The smooth time-resolved signal intensities of elements, steep wall, and flat bottom of ablation craters also suggested homogeneity in the depth profile. Line profile analyses across the entire pressed pellet further demonstrated that the pellet is homogenous for the investigated elements. The concentrations of major and trace elements in MtTR-1 determined by ICP-OES and ICP-MS are used as the preferred values. The MtTR-1 can be cut into slices, repeatedly polished and used for in situ analyses. The proposed technique for producing magnetite can also be applicable to other minerals or rocks by optimizing the conditions, thus providing a new method for preparing reference materials for in-situ microanalysis.


Behind all efforts in increasing the income of tourism and hotel industry, the
housekeeping department plays very important roles. The writer decided to
participate in a job training program of a hotel to get more information about
housekeeping department. The writer experienced a three-month job training as a
housekeeping attendant. The writer had done the daily job of a public area
attendant, laundry attendant, uniform and linen attendant, and room attendant in
Jogjakarta Plaza Hotel. As the result of the job training, the writer got the
information needed in making this report. From the job training experience, the
writer concluded that housekeeping department of a hotel is very important. The
department keeps the facilities of the hotel well maintained. Therefore, the hotel
can maximize its services. The services of the hotel make the guests comfortable
and give a good impression to the guests. Many guests of the hotel are "repeat
visitors" which means that the guest had been in the hotel before and come to the
hotel again on other occasions. The facts above make Jogjakarta Plaza Hotel
become one of the best hotels in Yogyakarta.


Abstract A direct numerical simulation (DNS) based on the lattice Boltzmann method (LBM) is carried out in low-Reynolds-number grid turbulence to analyse the mean turbulent kinetic energy dissipation rate, $\overline{\epsilon }$ , and its transport equation during decay. All the components of $\overline{\epsilon }$ and its transport equation terms are computed, providing for the first time the opportunity to assess the contribution of each term to the decay. The results indicate that although small departures from isotropy are observed in the components of $\overline{\epsilon }$ and its destruction term, there is sufficient compensation among the components for these two quantities to satisfy isotropy to a close approximation. A short distance downstream of the grid, the transport equation of $\overline{\epsilon }$ simplifies to its high-Reynolds-number homogeneous and isotropic form. The decay rate of $\overline{\epsilon }$ is governed by the imbalance between the production due to vortex stretching and the destruction caused by the action of viscosity, the latter becoming larger than the former as the distance from the grid increases. This imbalance, which is not constant during the decay as argued by Batchelor & Townsend (Proc. R. Soc. Lond. A, vol. 190, 1947, pp. 534–550), varies according to a power law of $x$ , the distance downstream of the grid. The non-constancy implies a lack of dynamical similarity in the mechanisms controlling the transport of $\overline{\epsilon }$ . This is consistent with the fact that the power-law-decay ( $\overline{q^2} \sim x^n$ ) exponent $n$ is not equal to $-$ 1. It is actually close to $-$ 1.6, a value in keeping with the relatively low Reynolds number of the simulation. These results highlight the importance of the imbalance in establishing the value of $n$ . The $\overline{\epsilon }$ -transport equation is also analysed in relation to the power-law decay. The results show that the power-law exponent $n$ is controlled by the imbalance between production and destruction. Further, a relatively straightforward analysis provides information on the behaviour of $n$ during the entire decay process and an interesting theoretical result, which is yet to be confirmed, when $R_{\lambda } \rightarrow 0 $ , namely, the destruction coefficient $G$ is constant and its value must lie between $15/7$ and $30/7$ . These two limits encompass the predictions for the final period of decay by Batchelor & Townsend (1947) and Saffman (J. Fluid Mech., vol. 27, 1967, pp. 581–593).


Liquid plug propagation and rupture occurring in lung airways can have a detrimental effect on epithelial cells. In this study, a numerical simulation of a liquid plug in an infinite tube is conducted using an Eulerian–Lagrangian approach and the continuous interface method. A reconstruction scheme is developed to allow topological changes during plug rupture by altering the connectivity information about the interface mesh. Results prior to the rupture are in reasonable agreement with the study of Fujioka et al. in which a Lagrangian method is used. For unity non‐dimensional pressure drop and a Laplace number of 1000, rupture time is shown to be delayed as the initial precursor film thickness increases and rupture is not expected for thicknesses larger than 0.10 of tube radius. During the plug rupture process, a sudden increase of mechanical stresses on the tube wall is recorded, which can cause tissue damage. The peak values of those stresses increase as the initial precursor film thickness is reduced. After rupture, the peaks in mechanical stresses decrease in magnitude as the plug vanishes and the flow approaches a fully developed behavior. Increasing initial pressure drop is shown to linearly increase maximum variations in wall pressure and shear stress. Decreasing the pressure drop and increasing the Laplace number appear to delay rupture because it takes longer for a fluid with large inertial forces to respond to the small pressure drop. Copyright © 2010 John Wiley & Sons, Ltd.


Metabolic engineering aims to improve the production of desired biochemicals and proteins in organisms and therefore, plays a central role in Biotechnology. However, the design of overproducing strains is not straightforward due to the complexity of metabolic and regulatory networks. Thus, theoretical tools supporting the design of such strains have been developed. One particular method, CASOP, uses the set of elementary flux modes (EFMs) of a reaction network to propose strategies for the overproduction of a target compound. The advantage of CASOP over other approaches is that it does not consider a single specific flux distribution within the network but the whole set of possible flux distributions represented by the EFMs of the network. Moreover, its application results not only in the identification of candidate loci that can be knocked out, but additionally proposes overexpression candidates. However, the utilization of CASOP was restricted to small and medium scale metabolic networks so far, since the entire set of EFMs cannot be enumerated in such networks. This work presents an approach that allows to use CASOP even in genome-scale networks. This approach is based on an estimation of the score utilized in CASOP through a sample of EFMs within a genome-scale network. Using EFMs from the genome-scale metabolic network gives a more reliable picture of the metabolic capabilities of an organism required for the design of overproducing strains. We applied our new method to identify strategies for the overproduction of succinate and histidine in Escherichia coli. The succinate case study, in particular, proposes engineering targets which resemble known strategies already applied in E. coli. Availability: Source code and an executable are available upon request.


Purpose - The Aim of this study is to determine and to compare the impact of fat excess on neuromuscular performances during short maximal exercise in male and female students. Methods - 72 male and 64 female students aged 20 to 23 years were enrolled in this study. After assessing their morphological characteristics (body mass, height and percentage of fat mass), a squat jump test (SJ), a 5 successive jump test (5JT), a hand gripping (HG) and back strength (BS) tests have been conducted for each subject. Male students were re-tested after being weighed down with a weight equivalent to the mean differences in body fat recorded between the two sexes in the form of a loaded worn vest. Results – Male are 15.7% heavier and 7.4% taller and presented a percentage of fat mass (17.2 ± 1.8%) significantly (p<0.001) lower than that of women subject (25.0 ± 2.5%) (difference male vs female for fat mass: -45.5%). HG, BS, 5JT and SJ performances were significantly higher in males (44±5 kg, 141±2 kg, 11±1 m and 32.4 ± 2,7 cm, respectively) than in females (31.0±4 kg, 81.6±13 kg, 8.7 ± 0.7 m and 21.1 ± 1.9 cm, respectively. In the control (unloaded) condition, the relative difference between males and females represented 23.5% and 34.7% of the male performances for 5JT and SJ, respectively. In the weighted condition, the relative difference between weighted males and females still represented 11.7% and 23.8% of the weighted male performances for 5JT and SJ, respectively. Cancelling the sex difference in fat mass by adding weight in males reduced by 50.1% the sex difference during 5JT and 31.4% and 71.7% for hight and power results, respectively during SJ test. Conclusion – During short and maximal exercise, male performed better with their hands, back and legs than female students. Excess fat for female students have a disadvantageous effect on vertical and horizontal jumps performances. The persistence of sex differences after weighting of male students indicates that body fat is responsible for 30 to 70 % of the observed differences between sexes performances and power outcome during jump tests.


Language mirrors understanding of the same or other culture. Meaning is hardly encoded in the world community. Some linguists cannot solve language problems because of its abstractedness. Language communicators learn the second or foreign language at schools for three reasons. First, English is not their first language. Second, they have little or no educational background in experiencing what they know in another language. Third, they have not improved their communication skills in English. Analyzing the language as a mean of communication would not be learned enough without its practice. This paper gives an exclusive preview of applied linguistics. It defines the conversion of different areas of the study of language with second or foreign language education. The connection and distinction between applied linguistics and language teaching is addressed in the study comprehensively. The findings of this review suggests that the two areas need further investigation in the education system.


Astragalus argaeus is critically endangered endemic species growing only on Erciyes Mountain in Kayseri. Inter simple sequence repeat (ISSR) markers were chosen to detect the genetic diversity in four populations of A. argaeus. Ten primers were used to assess the diversity among 96 genotypes collected from the four localities in Erciyes Mountain. A total of 78 bands were scored, of which 44 (55.8%) were polymorphic. The unweighted pair group method arithmetic average (UPGMA) and principle component analysis (PCoA) showed moderate genetic diversity at the species and population level. The percentages of polymorphic bands (PPB) ranged from 53.8 to 61.5 (58.01% ± 3.2) and average gene diversity (h) at the population and species level was estimated to be 0.17 and 0.23, respectively. The Shannon's information index (SI) ranged from 0.24 to 0.29 at the population level and was 0.35 at the species level. The determined gene flow (Nm) was 1.83. The UPGMA tree indicated that the four populations were not genetically distinct obviously. In analysis of molecular variance (AMOVA), the percentage of the variance was 38.72% among populations and 61.28% within populations. The data which small population size, habitat fragmentation and moderate levels of genetic diversity demonstrate that A. argaeus possess threat of extinction if its narrow habitat is destroyed.


In this paper I investigate the usability of the characteristic functions for the description of the dynamics of open quantum systems focussing on non-Lindblad-type master equations. I consider, as an example, a non-Markovian generalized master equation containing a memory kernel which may lead to nonphysical time evolutions characterized by negative values of the density matrix diagonal elements [S. M. Barnett and S. Stenholm, Phys. Rev. A 64, 033808 (2001)]. The main result of the paper is to demonstrate that there exist situations in which the symmetrically ordered characteristic function is perfectly well-defined while the corresponding density matrix loses positivity. Therefore, nonphysical situations may not show up in the characteristic function. As a consequence, the characteristic function cannot be considered an alternative complete description of the non-Lindblad dynamics.


INTRODUCTION Graphical editing, like many applications facilitated by computers, often involves repetitive tasks. To reduce repetition, programmers can write procedures to automate these tasks, however most users do not know how to program, and the repetitive tasks that they perform are frequently too specialized for the application programmer to anticipate. End users would benefit from the ability to customize and extend their applications for the tasks they usually perform.


Prokinetic agents, specifically 5-hydroxytryptamine type 4 (5-HT4) receptor agonists, have been shown to provide relief in chronic idiopathic constipation (CIC). The first-generation 5-HT4 agonists were initially withdrawn from use owing to associations with serious cardiovascular (CV) events. This review summarizes CV safety data for prucalopride, a high-affinity 5-HT4 agonist approved in the United States in 2018 for adults with CIC. No significant effects of prucalopride on CV safety were observed in animal models or early-phase clinical studies, including a thorough QT study at therapeutic (2 mg) or supratherapeutic (10 mg) doses. Among 1,750 patients with CIC who received prucalopride (2–4 mg) in 5 phase 3 studies, no trends in CV adverse events, electrocardiogram parameters, or blood pressure were documented; ≤1.0%–2.0% of patients had prolonged QT interval corrected for heart rate (HR) using Fridericia formula after placebo or prucalopride treatment, and low HR occurred in ≤6.1% and ≤3.3% of these patients, respectively. In two 24-month observational studies among 2,468 patients, changes in electrocardiogram parameters over time were minor, except at occasional time points when significant changes from baseline were reported for HR or QT interval. In a real-world European CV safety study among 35,087 patients (prucalopride, 5,715; polyethylene glycol 3350 [PEG3350], 29,372), results were consistent for no evidence of increased risk of major adverse CV events among patients treated with prucalopride vs PEG3350 (incidence rate ratio = 0.64; 95% confidence interval 0.36–1.14). Studies to date have not raised concerns regarding the impact of prucalopride treatment on CV parameters.