Familial Alzheimer's disease-associated mutations in presenilin 1 or 2 or amyloid precursor protein result in elevated β-amyloid, β-amyloid accumulation, and plaque formation in the brains of affected individuals. By crossing presenilin 1 transgenic mice carrying the A246E mutation with plaque-producing amyloid precursor protein K670N/M671L transgenic mice (Tg2576), we show that co-expression of both mutant transgenes results in acceleration of amyloid accumulation and associative learning deficits. At 5 months of age with no detectable plaque pathology, amyloid precursor protein transgenic animals are impaired in contextual fear learning following two pairings of conditioned and unconditioned stimuli but appear normal following a more robust five-pairing training. At 9 months of age when β-amyloid deposition is evident, these mice are impaired following both two-pairing and five-pairing protocols. Mice carrying both transgenes are impaired in contextual fear conditioning at either age. All transgenic animal groups performed as well as controls in cued fear conditioning, indicating that the contextual fear learning deficits are hippocampus-specific. The associative learning impairments are coincident with elevated α7 nicotinic acetylcholine receptor protein in the dentate gyrus. These findings provide two robust and rapid assays for β-amyloid-associated effects that can be performed on young animals: impaired contextual fear learning and up-regulation of α7 nicotinic receptors.


A new case of IgE lambda paraproteinaemia is described in which the immunoproliferative disorder was lympho-plasmacytoid, rather than myelomatous in type. The patient, an 81-year-old woman, lacked both organomegaly and bone lesions. The peripheral white blood count was 30 X 10(9)/l (43% lymphocytes and 37% lymphoplasmacytoid cells) and the bone marrow was heavily infiltrated with mononuclear cells with 50% lymphocytes and 50% lymphoplasmacytoid cells). Detailed immunological marker analysis of both peripheral blood and marrow showed an increased population of morphologically normal T cells, together with neoplastic population of B cells. The neoplastic cells were shown to re-express surface immunoglobulin after stripping with anti-E anti-serum, and to synthesis Ig in radio-incorporation experiments. The immunological characteristics of the neoplastic cells are considered in relation to B-cell maturation and it is shown that the immunological phenotype was of the intermediate type to be expected in association with a lympho-plasmacytoid proliferation.


The timing of the switch from vegetative to reproductive development is crucial for species survival. The plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this switch in Arabidopsis, in part via the direct activation of two other meristem identity genes, APETALA1 (AP1) and CAULIFLOWER (CAL). We recently identified five new direct LFY targets as candidates for the missing meristem identity regulators that act downstream of LFY. Here, we demonstrate that one of these, the class I homeodomain leucine-zipper transcription factor LMI1, is a meristem identity regulator. LMI1 acts together with LFY to activate CAL expression. The interaction between LFY, LMI1 and CAL resembles a feed-forward loop transcriptional network motif. LMI1 has additional LFY-independent roles in the formation of simple serrated leaves and in the suppression of bract formation. The temporal and spatial expression of LMI1 supports a role in meristem identity and leaf/bract morphogenesis.


In this paper, a review of the authors' work on inkjet-printed flexible antennas, fabricated on paper substrates, is given. This is presented as a system-level solution for ultra-low-cost mass production of UHF radio-frequency identification (RFID) tags and wireless sensor nodes (WSN), in an approach that could be easily extended to other microwave and wireless applications. First, we discuss the benefits of using paper as a substrate for high-frequency applications, reporting its very good electrical/dielectric performance up to at least 1 GHz. The RF characteristics of the paper-based substrate are studied by using a microstrip-ring resonator, in order to characterize the dielectric properties (dielectric constant and loss tangent). We then give details about the inkjet-printing technology, including the characterization of the conductive ink, which consists of nano-silver particles. We highlight the importance of this technology as a fast and simple fabrication technique, especially on flexible organic (e.g., LCP) or paper-based substrates. A compact inkjet-printed UHF ldquopassive RFIDrdquo antenna, using the classic T-match approach and designed to match the IC's complex impedance, is presented as a demonstration prototype for this technology. In addition, we briefly touch upon the state-of-the-art area of fully-integrated wireless sensor modules on paper. We show the first-ever two-dimensional sensor integration with an RFID tag module on paper, as well as the possibility of a three-dimensional multilayer paper-based RF/microwave structure.


This empirical study aimed to find out the soil condition to achieve maximum plant growth using cow dung manure and to compare it with soil without any manure. The experiment was done in an area of 4.5m2 divided into six plots of 0.75m2. Five plots were with varied percentages of cow dung manure. Plots 1,2,3,4 and 5 were conditioned with 100,50,40,30, and 20 percent of cow dung manure with that of the soil proportion, respectively. However, plot 6 was with no manure. Measurement of the plant's height, leaf's length and width, number of nodes, and branches in all the plots were measured periodically. The researchers identified and measured the different proportion of cow dung manure and its direct impact on the plant growth comparing with the plot with no manure. Results in the plots with 50 and 40 percent of cow dung manure produced healthy and large leaves, growth of the plants were supported with sufficient nutrients and micro-organisms compared to plots 1, 4, and 5. The plot with no manure showed the opposite of all other plots. Implication of this paper was to scientifically determine the right amount of cow dung manure and soil proportion for optimizing plant growth.


Principal component analysis (PCA) is an exploratory tool widely used in data analysis to uncover the dominant patterns of variability within a population. Despite its ability to represent a data set in a low-dimensional space, PCA's interpretability remains limited. Indeed, the components produced by PCA are often noisy or exhibit no visually meaningful patterns. Furthermore, the fact that the components are usually non-sparse may also impede interpretation, unless arbitrary thresholding is applied. However, in neuroimaging, it is essential to uncover clinically interpretable phenotypic markers that would account for the main variability in the brain images of a population. Recently, some alternatives to the standard PCA approach, such as sparse PCA (SPCA), have been proposed, their aim being to limit the density of the components. Nonetheless, sparsity alone does not entirely solve the interpretability problem in neuroimaging, since it may yield scattered and unstable components. We hypothesized that the incorporation of prior information regarding the structure of the data may lead to improved relevance and interpretability of brain patterns. We therefore present a simple extension of the popular PCA framework that adds structured sparsity penalties on the loading vectors in order to identify the few stable regions in the brain images that capture most of the variability. Such structured sparsity can be obtained by combining, e.g.,  $\ell _{1}$  and total variation (TV) penalties, where the TV regularization encodes information on the underlying structure of the data. This paper presents the structured SPCA (denoted SPCA-TV) optimization framework and its resolution. We demonstrate SPCA-TV's effectiveness and versatility on three different data sets. It can be applied to any kind of structured data, such as, e.g.,  ${N}$ -dimensional array images or meshes of cortical surfaces. The gains of SPCA-TV over unstructured approaches (such as SPCA and ElasticNet PCA) or structured approach (such as GraphNet PCA) are significant, since SPCA-TV reveals the variability within a data set in the form of intelligible brain patterns that are easier to interpret and more stable across different samples.


Abstract. After focusing on the changes in Hungarian temperature and preeipitation during this Century, possible hydrological, agricultural and ecological consequences of a future climate change are described. These results have been obtained using a modified version of empirical downscaling techniques, developed to analyse the local effects of global climate change in a twofold concentration of atmospheric greenhouse gases scenario. In addition, regional changes in temperature and precipitation were examined with the help of the more specific stochastic downscaling method. The climate of Hungary has become warmer and drier over the last Century. It is to be expected that an increasing concentration of atmospheric greenhouse gases will enhance the tendency towards aridification.


Rabies is a major zoonosis for which diagnostic techniques have been standardised internationally. Laboratory techniques are preferably conducted on central nervous system (CNS) tissue removed from the cranium. Agent identification is preferably done using the fluorescent antibody test. A drop of purified immunoglobulin previously conjugated with fluorescein isothiocyanate is added
to an acetone-fixed brain tissue smear, preferably made from several parts of the brain, including the hippocampus, cerebellum and medulla oblongata. For a large number of samples, as in an epidemiological survey, the immunoenzyme technique can provide rapid results (the rapid rabies enzyme immunodiagnosis). FAT provides a reliable diagnosis in 98-100% of cases for all genotypes if a potent conjugate is used, while RREID detects only genotype 1 virus. Infected neuronal cells have been demonstrated by histological tests and these procedures will reveal aggregates of viral material (the Negri bodies) in the cytoplasm of neurones. However, the sensitivity of histological techniques is much less than that of immunological methods, especially if there has been some autolysis of the specimen. Consequently, histological techniques can no longer be recommended. As a single negative test on fresh material does not rule out the possibility of infection, inoculation tests, or other tests, should be carried out simultaneously. Newborn or 3-4-week-old mice are
inoculated intracerebrally with a pool of several CNS tissues, including the brain stem, and then kept under observation for 28 days. For any mouse that dies between 5 and 28 days, the cause of death should be confirmed by FAT. Alternatively, a monolayer culture of susceptible cells is inoculated with the same material as used for mice. FAT carried out after appropriate incubation will demonstrate the presence or absence of viral antigen. Wherever possible, virus isolation in cell culture should replace mouse inoculation tests. The identification of the agent can be supplemented in specialised laboratories by identifying any variant virus strains through the use
of monoclonal antibodies, specific nucleic acid probes, or the polymerase chain reaction followed by DNA sequencing of genomic areas. Such techniques can distinguish between field and vaccine strains, and possibly identify the geographical origin of the field strains. Virus neutralisation assays in cell cultures are the prescribed tests for international trade.


Driven by critical and pressing smart city applications, accessing massive numbers of sensors by cloud-hosted services is becoming an emerging and inevitable situation. Naïvely connecting massive numbers of sensors to the cloud raises major scalability and energy challenges. An architecture embodying distributed optimization is needed to manage the scale and to allow limited energy sensors to last longer in such a dynamic and high-velocity big data system. We developed a multi-tier architecture which we call Cloud, Edge and Beneath (CEB). Based on CEB, we propose an Application Fragment Caching Algorithm (AFCA) which selectively caches application fragments from the cloud to lower layers of CEB to improve cloud scalability. Through experiments, we show and measure the effect of AFCA on cloud scalability.


The performance of the critical systems is one of the major concerns in modern industrial plants. The workhorses of these systems are induction motors consuming around 80% of the power. Periodic monitoring of these motors is based on a personal computer implementation that is performed offline. Such a monitoring system requires an expert interpretation. This paper presents a new methodology for fault detection, which is based on observing some frequency components of zero crossing points by using signal spectrum. The amplitude of ZCT signal and amplitude of fault related frequency are evaluated by fuzzy inference system to identify broken rotor bar faults. The proposed system is implemented on single low-cost field-programmable-gate-arrays (FPGA). The algorithm was performed using some experimental tests for validating the implementation.


The reinforced concrete construction of port, wharf, inshore platform etc, which expose in the bad environment, can suffer influence of the corrosion and lower its safety. Particularly with the seawater corrosion, the reinforced concrete construction will suffer to break easily and result a bigness of loss. Therefore, the construction's safe and dependable increasingly become the important problem that study by people. The paper tested the load about 15 experiment columns of reinforced concrete, which are eroded in the artificial seawater corrosion, studied the load changing of reinforced concrete column which in different times of suffering decay. It afforded the basis for analysis the load of reinforced concrete construction in the corrosion environment.


An exploratory, qualitative, study into the views of teachers on the use of comic books in education was carried out. Three secondary school teachers with varying experiences of comic books were interviewed using an open-ended format. Results of a thematic analysis indicated three clear
 areas of thinking around comic books: firstly, comic books are considered to be a medium of children's entertainment, and not associated with educational practice; secondly, when the medium is employed in education, it should primarily be used with students that require extra support
 and thirdly, comic books represent a 'missed opportunity in education' and have not achieved their full potential due to a lack of comic book resources for use in the classroom. All three concepts are discussed in light of research evidence supporting the use of comics in educational
 contexts and concerns are highlighted that suggest these themes might represent a barrier to the future use of comics in these areas. Further qualitative and quantitative research to expand these initial findings is also suggested.


This paper focuses on transformational processes in a post Paris agreement context. It uses IMACLIM-R, an E3 (Environment–Energy–Economy) model allowing for the integration of urban forms, transport dynamics, environmental policies and behaviors. Building upon the study of a set of local low carbon experiments throughout the European Union (EU), the paper explores two contrasted stylized scenarios of the low carbon transition in Europe. It highlights that carbon pricing policies are useful guides for transition but cannot achieve the ambitious objective without significant transition costs. It shows that low carbon experiments in the transport and energy sectors are critical dimensions of complementary measures in favor of green infrastructures. Broadening and upscaling low carbon experiments helps overcome the inertias of the transport sector by fostering radical changes in infrastructures, thereby introducing deep transformations in mobility behavior. This can then generate positive macroeconomic outcomes, even though they are also dependent on specific financial support, calling for a renegotiation of the social contract based on specific fiscal reforms and measures to secure funding for these initiatives. The paper concludes with some research avenues for improving this preliminary work and calls for a better understanding of the complexity of the socio-economic patterns of both the transition and the conditions for an effective implementation.


Fisheries usually first remove large predators before switching to smaller species, causing lasting changes to fish community structure. Reef fish provide essential protein and income for many people, and the impacts of commercial and high-intensity subsistence fishing on reef fish are well documented. However, how fish communities respond to low levels of subsistence fishing using traditional techniques (fishing for food, few fishers) is less well understood. We use three atolls in the Marshall Islands as a model system to quantify effects of commercial and subsistence fishing on reef fish communities, compared to a near-pristine baseline. Unexpectedly, fish biomass was highest on the commercially-fished atoll where the assemblage was dominated by herbivores (50% higher than other atolls) and contained few top predators (70% lower than other atolls). By contrast, fish biomass and trophic composition did not differ between pristine and subsistence-fished atolls - top predators were abundant on both. We show that in some cases, reefs can support fishing by small communities to provide food but still retain intact fish assemblages. Low-intensity subsistence fishing may not always harm marine food webs, and we suggest that its effects depend on the style and intensity of fishing practised and the type of organisms targeted.


In an effort to gain a better understanding into the role played by food animals in the epidemiology of gastrointestinal parasites, we assessed the prevalence of  gastrointestinal parasites in different breeds of rams brought into Abeokuta during a festive  season by microscopic examination of faecal samples. A total of 206 rams of different breeds were randomly sampled. The faecal samples collected were  subjected to simple floatation and sedimentation tests. McMaster egg counting  technique was used to estimate the faecal oocyst load in positive samples. Overall prevalence of gastrointestinal parasites was 51.46%. There was significant (p < 0.05) difference between the prevalence of Eimeria spp (37.38%)and helminth eggs (13.59%).Among the 29 samples that tested positive for helminth eggs, 6 (20.7%), 19 (65.5%) and 4 (13.8%) were cestode, nematode and trematode eggs,  respectively. The genera of nematodes eggs identified include Strongyloides spp, Haemonchus spp, Mashallagia spp,  Bunostomum spp, Ascaris spp, Dictyocaulus spp, Gongylonema spp and Ostergia spp; trematodes were Fasciola spp and Dicrocoelium spp while cestodes were Moniezia spp and Avitellinaspp. The only protozoan parasite identified was Eimeria spp. This study has  clearly shown that rams brought to Abeokuta during festive seasons carry different gastrointestinal parasites of which Eimeria spp had the largest share. Parasites of zoonotic importance (Fasciola and Moniezia) were also detected. Therefore, there is need for  regular screening of animals being introduced from one state to the other and also from neighbouring countries for effective  monitoring and control of parasitic diseases in domestic animals and human population.Keywords: GIT parasite, ram, helminth, protozoan.


The purpose of this work was to investigate effects of zonal variations in salinity within the rootzone on chloride uptake and accumulation by grapevines under glasshouse conditions. Rootzone variations in salinity were produced by irrigating sloping sand cultures, held in 60 cm long cylinders, either at the surface or at 20 cm or 40 cm below the surface. Experiments involved vines with either established (roots occupied the length of slopes at day 1 of salt treatment) or developing (roots occupied only top 10 cm of slopes at day 1 of salt treatment) root systems. In all experiments, chloride only accumulated in root tissues which were present or grew into salt affected zones within sand slopes. Salinity (25 mM NaCl) increased petiole chloride concentrations of Sultana vines with established root systems after 28, 56 and 79 days. The magnitude of this increase varied according to the extent of the root system affected by salt. Petiole chloride concentrations were greatest when an entire root system was salt affected and least when only one-fifth was affected. In three experiments involving vines with developing root systems, roots grew into zones which were irrigated with NaCl (50 mM). In two of these experiments, one with Ramsey and the other with Sultana vines, NaCl had no effect on root growth. Root dry weight in the third experiment (comparing Ramsey and Sultana) was significantly reduced by salinity, although the proportions of root systems (based on total dry weight) within the three zones of the root profile were the same as those for control vines. With developing root systems, both Ramsey and Sultana vines accumulated significantly greater chloride concentrations in petioles compared to controls when the entire root system was treated with NaCl (50mM) for 60 days. In two experiments, the first with Ramsey and the second with Sultana vines, chloride did not accumulate in petioles in concentrations significantly greater than corresponding controls when roots grew from non-saline to saline zones. In the third experiment (comparing Ramsey and Sultana vines) chloride accumulated in shoots when roots grew into salt affected zones, but there were no differences, with the exception of proximal and distal petioles, in shoot chloride concentrations between these two cultivars. In all experiments, petiole chloride concentrations within shoots increased basipetally. Results are discussed in relation to assessing variation in chloride accumulation by hybrid grapevines.


Purpose
An outcome bias occurs when performance is evaluated based upon the outcome of the decision rather than upon the quality of the decision itself. The purpose of this paper is to test experimentally whether advisors eliminating the uncertainty in the quality of decisions as a potential driver of the outcome bias can eliminate this bias in judgements. Additionally, the paper analyses whether such advisors can attenuate the emotional experience after decisions' outcomes by supporting the cognitive understanding of these outcomes.

Design/methodology/approach
The paper employs a between-subject experimental setting where decision makers are asked to make investment decisions. The two variables manipulated were advice (receiving advice vs deciding without an advice) and state (loss vs neutral vs gain state). Participants were randomly assigned to each group. One group completed all tasks while receiving advice before making a final decision. Another group completed all tasks without any advice. After completing each investment task, participants were randomly assigned to one of three possible states that determine their payoff.

Findings
The results reveal that advisors eliminating the uncertainty in the quality of decision can eliminate the outcome bias in the judgements of decision quality, especially after bad outcomes. Nevertheless, after controlling for the perceived quality of the decisions, advised individuals show a greater emotional sensitivity to bad outcomes than non-advised decision makers. These observations suggest that advisors eliminating the uncertainty in the decision quality can improve the understanding that good decisions can lead to bad outcomes just by chance, but they are not able to prevent affective reactions after bad outcomes; on the contrary, they may even reinforce them.

Research limitations/implications
The observation that, after bad outcomes, advised decision makers are less willing to decide the same way than non-advised decision makers is consistent with empirical findings on the risk-taking behaviour of self-directed and mutual fund investors. Self-directed investors are less likely to revise their decision and sell an investment at a loss than mutual fund investors (Chang et al., 2016). While investors might sell funds because they are unable to observe the decision process of the manager and use the outcome to judge the manager's skills, this study shows that such learning from decision outcomes is not necessary for observing the risk-taking behaviour of the investors. Even if the decision process of the advisor is observable (as in this study), the decision makers' willingness to decide the same way is influenced by the losses – an effect that goes beyond the assessed quality of advice as the results of this study show.

Practical implications
The results of this study have important implications for advisors aiming to maintain a positive relationship with their clients. Convincing clients that an advice is optimal supports their understanding that a good advice can have bad outcomes. However, this understanding may not prevent affective reactions after bad outcomes. On the contrary, the affective response after bad outcomes is even stronger with the advice than without it. Hence, advisors should address not only issues related to the quality of the provided advice, but also emotional aspects, which could be related to what clients expect from following the advice.

Originality/value
This study is one of the few that account for the possibility that the outcome bias may arise because there is uncertainty regarding the optimal choice. In particular, this paper uses a much more powerful criterion to define an optimal choice than the expected value criterion used in previous studies. The criterion represents a minimal requirement for rational behaviour in expected utility theory and many non-expected utility theories.


As with the curation of any large group show, this project involved a long and intensive period of research and development, including a careful selection of works and artists, toward the eventual coordination and design of a cohesive exhibition built around a central theme. This work was undertaken in collaboration with co-curator Peggy Atherton. The exhibition was held at the Tablet, which was then under the direction of Mark Wilsher.


Objective The prevalence, patients' age and sex and the site of the lesions are important factors for diagnosis and they may be different in various populations. The aim of this study was to determine the type and distribution of orofacial tumors among children and adolescents in an Iranian population Methods In this retrospective, case series study, data about the type, age, sex and site of 142 tumors in patients ≤18 years afflicted with orofacial neoplasms referred 2005-2009 to two referral centers in Shiraz, Southern Iran, were collected and analyzed. Findings There were 142 (2.8%) tumors among the subjects. The most common types of benign and malignant tumors were odontoma and lymphoma in children and pleomorphic adenoma and rhabdomyosarcoma in adolescents. Parotid and posterior parts of the mandible were the most common sites of soft tissue and intrabony tumors. In the oral cavity, the palate was the most common affected site. The tumors were found in boys with higher frequency (Male:Female ratio was 1.4:1). Conclusion The observed differences in tumor type and distribution in comparison with previous studies may be attributed to genetic and geographic variations in the populations; however the design and methods of the studies are different, too.


Background: Optimal management of cardiac implantable electronic devices (CIEDs) in patients with Ebstein anomaly during tricuspid valve (TV) surgery is unknown. Thus, we aimed to characterize CIED management/outcomes in patients with Ebstein anomaly undergoing TV surgery. Methods: Patients at the Mayo Clinic from 1987 to 2020 with Ebstein anomaly and CIED procedure were reviewed for procedural details, complications, echocardiogram, and lead parameters. Five-year cumulative incidence of CIED complications were estimated using the Kaplan-Meier method. Results: Ninety-three patients were included; 51 were female, and mean age was 40.7±17.5 years. A new CIED was implanted in 45 patients at the time of TV surgery with the majority receiving an epicardial (n=37) CIED. Among 34 patients who had preexisting CIED (11 epicardial, 23 transvenous) at time of TV surgery, 20 had a transvenous right ventricular lead managed by externalizing the lead to the TV (n=15) or extracting the transvenous lead with epicardial lead implantation (n=5). Fourteen patients underwent CIED implantation (4 epicardial, 10 transvenous) without concurrent surgery. Placement of lead across the TV was avoided in 85% of patients. The 5-year cumulative incidence of CIED complications was 24% with no significant difference between epicardial and transvenous CIEDs (26% versus 23%, P=0.96). Performance of lead parameters was similar in epicardial and transvenous leads during median (interquartile range) follow-up of 44.5 (61.1) months. Conclusions: In patients with Ebstein anomaly undergoing TV surgery, the use of epicardial leads and externalization of transvenous leads to the TV can avoid lead placement across the valve leaflets. Lead performance and CIED complications was similar between epicardial and transvenous CIEDs.


This paper's purpose is to review the recent experience of foreign direct investment (FDI) in North East England, and to explore the implications of this for the region's prospective economic development. Foreign-owned plants are reckoned to account for more than half the North East's employment in manufacturing, so that the future economic prospects of the region rest heavily on the performance of this stock of FDI plants. Further, the attraction of FDI continues to be a vital component of the region's economic strategy (One NorthEast, 2005), while the Regional Development Agency (RDA) supports initiatives to both develop and "embed" these plants in the region.


Background. In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the controversy surrounding this recommendation. Method. This study used a qualitative design to examine perceptions regarding susceptibility and screening. Data were collected at a community health center and three predominantly African American churches in North Carolina. Study participants were 46 African American men and women who attended one of four "listening sessions" for pretesting PCa educational materials (average age = 55 years). Listening sessions of 1.5-hour duration were conducted to pretest materials; while presenting the materials, researchers probed beliefs and knowledge about PCa screening. The sessions were recorded and transcribed, and the transcripts were qualitatively analyzed using grounded theory. Results. The four emergent themes indicated that participants (1) cited behavioral, psychosocial, and biological reasons why African American men have higher PCa risk compared with others; (2) knew about the controversy and had varying responses and intentions; (3) believed screening could save lives, so it should be used regardless of the 2012 recommendation; and (4) felt that women can help men go to the doctor and make screening decisions. Conclusion. Health education efforts to help community members understand health controversies, screening options, and how to make informed screening decisions are critical.


Background: Structural cardiac anomalies are neglected area of research among adolescents. Objectives: The objective of this study was to determine the pattern of presentation and clinical manifestations of structural cardiac diseases among adolescents attending UNTH, Enugu, Nigeria. Methods: An analysis of structural heart defects (congenital and acquired) seen among adolescents attending both the children outpatient clinic and cardiology clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu was undertaken over a five-year period. Results: A total of 778 echocardiography was done among children from day 1 to 24 years. Of these, 51 adolescents had echo confirmed structural heart disease. Forty-two (42/51) 82.4% had congenital heart disease. Their age ranged between 120 and 242 months with a mean age of presentation as 168 (36.5) months. The overall prevalence rates of structural heart diseases among these adolescents was (51/14,849) 0.34%; while that for congenital was (42/14849) 0.28% and that for acquired was (9/14849) 0.06%. The commonest congenital heart disease observed in these adolescents was ventricular septal defect (16/51) 31.4%, and Tetralogy of Fallot (TOF) (12/51) 23.5%, followed by AV canal defect (6/51) 11.8%. The commonest acquired heart disease is Rheumatic Heart Disease (RHD), and observed in 9.8% followed by cardiomyopathy seen in 7.8% of cases. Among those with congenital heart disease, surgery was performed in 31.8% of the subjects. However, following surgery, 78.6% (11/14) still has residual heart defect. Conclusions: The results of this study show that 0.34% per cent of adolescents who attended UNTH in Enugu State had cardiac abnormalities. The prevalence of congenital and acquired heart diseases was 0.28% and 0.06% respectively. The commonest forms seen were those with VSD and RHD.


Traditional assimilation paradigms argue that immigrants are particularly disadvantaged in feelings of marginality and dislocation. Given these paradigms, we explore how minority and immigrant status are associated with perceptions of social support among parents of young children. We use the Early Childhood Longitudinal Study—Kindergarten Cohort (ECLS-K), a nationally representative sample of children in kindergarten in 1998 and 1999. Most groups of minority immigrant parents, compared to their native-born white counterparts, report lower levels of perceived social support, and this gap persists even when demographic and socioeconomic characteristics are held constant. Additionally, English language ability, but not years spent in the United States, attenuates the disadvantages that Hispanic immigrant parents face in their perceptions of social support compared with white immigrant parents. Finally, Hispanic parents report substantial variation in their perceptions of social support by ethnicity. As social support is an important predictor of parents' economic stability and children's well-being, these findings have important implications for children of immigrants, an important and increasing demographic group in the United States.


Chatbots have gained increasing importance in today research with a lot of available applications. They are flexible and can be applied in many application domains. In tourism, Chatbots can recommend sights, hotels, activities, or even full travel plans. Usually, users are required to visit plenty of websites and install different Apps into their mobile phones in order to navigate the city and planning for the trip which is inconvenient and time-consuming. To address this issue, this paper proposes "Smart Guidance", an AI text-based chatbot that is developed as a mobile application. It simulates a chat with users in a natural language, it also provides a two-way interaction and it is a single point of contact for all user communications. We provide a use case in the city of Jeddah, Saudi Arabia. Jeddah is the second largest city in Saudi Arabia and tourists have various choices when it comes to moving around the city. The final evaluation of the chatbot showed that the bot could understand meanings and users' requests. Moreover, users found that the interaction is effective, and the responses are provided immediately. Users were satisfied and like the idea that they could express their needs in their natural language. Furthermore, users enjoyed the interaction and felt engaged. Keywords—Tourism, Chatbot, Natural Language Processing, Machine learning, Jeddah


Configurable processors are adopted by several latest embedded system projects to make use of application specific custom instructions for instruction level parallelism. Meanwhile, designers also use multiple processors for thread level parallelism. Configurable heterogeneous multi-processor system-on-chip (CH-MPSoC) has both parallelism advantages and seems to be a good solution for future embedded systems. Because CH-MPSoC has lots of architectural parameters, new design methodologies are required to help exploring this huge design space and finding a suitable solution for all user-defined constraints. We propose a new exploration flow using a budget based problem partitioning approach integrated with multiple abstraction levels. By using several abstraction levels, global budgets of speed, power and cost can be decomposed into detailed ones which are mapped onto each component. One special abstraction level called transaction accurate level is used in our flow to model both multi-processor architectures and configurable processors. At this level, hardware tasks and peripherals use transaction level modeling to achieve high simulation speed. Statistic information of configurable processors is abstracted and annotated to each software tasks. The execution results are used to adjust budgets and guide automatic extended instructions generation. With the Motion-JPEG case study, we illustrate detailed advantages of our CH-MPSoC exploration flow.


The Antarctic Ice Sheet (AIS) plays a major role in the evolution of Quaternary glacial-interglacial cycles
and in the global climate system in general. By a variety of ice-ocean and ice-atmosphere feedback
processes, changes in the dynamics of the southern ice giant are felt throughout the globe. Ice cores
drilled down to the bedrock of the East Antarctic Ice Sheet provide a glimpse into the climate history of
the past one million years via water stable isotopes and trapped gasses conserved in the slow flowing ice
(climate proxies). Dramatic changes in ice volume and extent characterize the evolution of the AIS during
the last 130.000 years, affecting both Southern Hemisphere and global climate. A central protagonist
in this history of the AIS is the West Antarctic Ice Sheet (WAIS), due to its unique setting extending
into several ocean basins and thus being prone to destabilization triggered by warming of the Southern
Ocean.
The objective of this thesis is to shed light on the glacial-interglacial dynamics of the AIS by means of
3D ice sheet modeling. The dynamic evolution of the WAIS during the Last Interglacial (LIG) and in the
future is investigated and potential climate thresholds for an marine ice sheet collapse identified. Special
attention is given to the role of basal melting underneath the ice shelves in the growth and decay of the
WAIS. An ocean warming range of 2


The focal research project will consider the nature and lived experience of 'talent management', a concept which has ascended the ranks of human resource management (HRM) practice over the last decade, through a gender and communications lens. The phrase 'talent management', however, is neither simple nor uncontentious to define or explain. Moreover, whilst the concept is much cited by HRM practitioners, there is a relative paucity of credible academic literature in the field.

This paper will evaluate the nature and meaning of 'talent management', specifically the two opposing claims that it is a revolutionary approach to ensuring a good supply of 'talent' (itself crucial to organisational success) as opposed to the stance that it is not a new HRM approach at all but merely a case of re-packaging and re-labelling of existing approaches. The position adopted here is that talent management embraces many of the traditional aspects of HRM, but within a talent 'culture'. Moreover, it is suggested that a strategic and contingent perspective of the concept and its operationalisation is warranted and, most significantly, that talent management policy and practice at the very least influences the lived experience of managers and the construction of 'talent'.


When the cost of global garbage collection in a system grows large, the system can be redesigned to use generational collection. The newly-created objects usually have a much shorter half-life than average, and by concentrating the collector's efforts on them a large fraction of the garbage can be collected at a tiny fraction of the cost.
The objects that survive generational collection may still become garbage, and the current practice is to perform occasional global garbage collections to purge these objects from the system, and again, the cost of doing these collections may become prohibitive when the volume of memory increases. Previous research has noted that the objects that survive generational collection often are born, promoted, and collected in large clusters.
In this dissertation I show that carefully selected semantically or structurally important key objects can be drawn from the clusters and collected separately; when a key object becomes unreachable, the collector can take this as a hint to collect the cluster from which the key was drawn.
To gauge the effectiveness of key objects, their use was simulated in ParcPlace's Object-works/Smalltalk system. The objects selected as keys were those that, as young objects, had pointers to them stored into old objects. The collector attempts to create a cluster for each key by gathering together all of the objects reachable from that key and from no previous key.
Using this simple heuristic for key objects, the collector finds between 41% and 92% of the clustered garbage in a suite of simple test programs. Except for one program in the suite, about 95% of the time these key objects direct the collector to a cluster that is garbage. The exception should be heeded in improving the heuristics. In a replay of an interactive session, key object collection finds 59% of the clustered garbage and 66% of suggested targets are indeed garbage.


This paper presents a novel procedure for creating a 3D torso image from a pair of stereo digital 2D back images. The aim of this procedure is to obtain 3D images that can be used for assessment of external spinal deformities in scoliosis. Scoliosis is a condition characterized by lateral deviation of the spine coupled with rotation of individual vertebra resulting in visible torso asymmetries. The procedure provides clinicians with a cost effective and mobile setup of acquiring 3D images. To improve the registration process, a novel approach combining tree weighted colour based image segmentation and differential geometry was developed. Image reconstruction involved pre-processing, triangulation and texture application to obtain a 3D image. Analysis was performed using human subjects and objects of known dimension. Evaluation of system performance was done against existing stereovision procedures and range scanning systems. The final 3D image was compared to that obtained from the Konica Minolta Vivid 700 laser scanner. Each image was divided into 360 cross sections for evaluation against size and shape. The 3D image reconstructed from this novel procedure was 75–100% accurate when compared against the 3D image from the laser scanner. The results demonstrate that the procedure is a cost effective clinical tool for assessing torso shape and symmetry.


Many cell surface proteins are anchored to the membrane via a glycosylphosphatidylinositol (GPI) moiety, which is attached to the C terminus of the proteins. The core of the GPI anchor is conserved in all eukaryotes but is modified by various side chains. We cloned a mouse phosphatidylinositol glycan-class N (Pig-n) gene that encodes a 931amino acid protein expressed in the endoplasmic reticulum, which is homologous to yeast Mcd4p. We disrupted the gene in F9 embryonal carcinoma cells. In thePig-n knockout cells, the first mannose in the GPI precursors was not modified by phosphoethanolamine. Nevertheless, further biosynthetic steps continued with the addition of the third mannose and the terminal phosphoethanolamine. The surface expression of Thy-1 was only partially affected, indicating that modification of the first mannose by phosphoethanolamine is not essential for attachment of GPI anchors in mammalian cells. An inhibitor of GPI biosynthesis, YW3548/BE49385A, inhibited transfer of phosphoethanolamine to the first mannose in mammalian cells but only slightly affected the surface expression of GPI-anchored proteins. Biosynthesis of GPI in thePig-n knockout cells was not affected by YW3548/BE49385A, and yeast overexpressing MCD4 was highly resistant to YW3548/BE49385A, suggesting that Pig-n and Mcd4p are targets of this drug.


The relentless pace of urbanization since the industrial revolution has inspired a continuing effort to view, read, and name the modern city. "We are now at a point of transition to a new kind of city", write William Sharpe and Leonard Wallock, "and thus we are experiencing the same crisis of language felt by observers of nineteenth- and early twentieth-century cities." "Visions of the Modern City" explores the ways in which artists and writers have struggled to define the city during the past two centuries and opens a new perspective on the urban vision of our time. In their introduction, the editors outline three phases in the evolution of the modern city-- each having its own distinctive morphology and metaphor-- and argue that a new vocabulary is needed to describe the sprawling "urban field" of today. Eric Lampard draws a detailed demographic and geographic picture of urbanization since the late eighteenth century, culminating with the "decentered" city of the 1980s. Other contributors examine the representation of cities from the London and Paris of 1850 to the New York, Los Angeles, and Tokyo of the present. Deborah Nord and Philip Collins follow Henry Mayhew and Charles Dickens, respectively, through the urban underworld of Victorian London. Theodore Reff traces the double life of Paris expressed in the work of Manet, while Michele Hannoosh shows bow Baudelaire influenced the Impressionists by transferring the aesthetic implications of the term nature to urban experience. Thomas Bender and William Taylor focus on tensions between the horizontal and the vertical in the architectural development of New York City, and Paul Anderer investigates the private, domestic spaces that represent Tokyo in postwar Japanese fiction. Steven Marcus analyzes the breakdown of the city as signifying system in the novels of Saul Bellow and Thomas Pynchon, writers who question whether the indecipherable contemporary city has any meaning left at all.


A new species Anthrenus (Florilinus) loebli from Israel, Lebanon and Jordania is described, illustrated and compared with the similar species classified within the subgenus Florilinus Mulsant & Rey, 1868. The new species is characterized by oval eyes, eight-segmented antenna and subtriangular, occasionally triangular, scales on the dorsum. The yellowish/light brown scales are present on the anterior and terminal part of the elytra and create three irregular, transverse bands. Antennal segment eight are at least 4.8 to 5x longer than segment 7 in male, 2.1x longer in female. The new species is most similar to A. (F.) museorum (Linnaeus, 1761); A. (H.) fuscus Olivier, 1789 and A. (F.) flavidus Solsky, 1876. An identification key to externally similar species of the genus is given. The most distinctive taxonomic characteristics concern the male genitalia and antenna (in ratio of length of segments of antennal club) and are also described.


A clear understanding of nuclear parton distribution functions (nPDFs) plays a crucial role in the interpretation of collider data taken at the Relativistic Heavy Ion Collider (RHIC), the Large Hadron Collider (LHC) and in the near future at the Electron-Ion Collider (EIC). Even with the recent inclusions of vector boson and light meson production data, the uncertainty of the gluon PDF remains substantial and limits the interpretation of heavy ion collision data. To obtain new constraints on the nuclear gluon PDF, we extend our recent nCTEQ15WZ+SIH analysis to inclusive quarkonium and open heavy-flavor meson production data from the LHC. This vast new data set covers a wide kinematic range and puts strong constraints on the nuclear gluon PDF down to $x\lesssim 10^{-5}$. The theoretical predictions for these data sets are obtained from a data-driven approach, where proton-proton data are used to determine effective scattering matrix elements. This approach is validated with detailed comparisons to existing next-to-leading order (NLO) calculations in non-relativistic QCD (NRQCD) for quarkonia and in the general-mass variable-flavor-number scheme (GMVFNS) for the open heavy-flavored mesons. In addition, the uncertainties from the data-driven approach are determined using the Hessian method and accounted for in the PDF fits. This extension of our previous analyses represents an important step toward the next generation of PDFs not only by including new data sets, but also by exploring new methods for future analyses.


This guide provides links to sources that teach searching skills and some resources that teach how libraries store information and provide tools to find sources in the library collections.


Upper gastrointestinal bleeding (UGIB) is one of the most common emergencies in gastroenterology practice. In recent years, the introduction of urgent upper gastrointestinal endoscopy (UGIE) and of the treatment with proton pump inhibitors (PPIs) in high doses has resulted in an improvement of the treatment outcome in patients with UGIB, but without a significant improvement in mortality rates. In our study we compared the epidemiological, clinical, therapeutic, and prognostic aspects in patients with non-variceal UGIB admitted over a period of one year in a tertiary center where urgent UGIE is a routine procedure and in a municipal hospital where UGIE with endoscopic hemostasis is not available. Patients admitted to the tertiary medical center had more clinical and endoscopic severity factors compared to those from the municipal hospital: they were older, with more frequent intake of NSAIDs, several comorbidities, some of them severe, and more severe posthemorrhagic anemia. The endoscopic examination revealed that active bleeding and stigmata of recent hemorrhage were more frequent in these patients. Urgent UGIE and, where necessary because of lesions, endoscopic hemostasis were performed in most of these patients. Patients admitted to the municipal hospital were treated more frequently with high-dose intravenous PPIs. Patients undergoing urgent UGIE and endoscopic therapy had a shorter duration of hospitalization. However, there were no differences regarding the need for surgery or mortality rates. The results of our study are consistent with the literature.


Even though the Spanish Constitution establishes that Spain is structured into Autonomous Communities and that the principles of solidarity and subsidiarity govern the relationship between the different regions, very often Spanish media publish news about territorial inequality, conflicts, and independency velleity. The objective of this investigation, avoiding digging into the reasons for these claims, is to identify whether the region of residence influences the legitimacy of the Spanish state. The legitimacy of the state is the degree of citizen's support to the institutions. This support ensures the law compliance, the proper functioning of the country and citizen commitment with the social system. State's legitimacy is very much linked with the trust on politics and politicians. In the regions characterized by independency issues and conflicts, state's legitimacy will be limited, and the perception of the state's meaning and power will be more fragile and instable. The effective and appropriate management of the state and the relevancy of the central politics would be complex in these regions and, finally, regional inequality and fragmentation will increase. To achieve this research objective, we carried out an analysis of the state's legitimacy of each Spanish region considering the data extracted from the European Social Survey. The results of this research provide valuable information useful for regional political decision making and dig into the reasons why regional conflicts are rooted in the state's institutions.


The concept of bank in India was formalized and conceptualized in the last decades of the 18th century. The first bank in India, though conservative, was established in 1786 in Calcutta by the name of bank of Bengal. The industry saw various ups and downs with failures and with a span of long journey, in the year 1935 RBI was created. Banking industry once again witnessed a makeover with nationalisation of banks in 1969 and a policy change introducing and infusing the LPG movement in the Indian economy. Abolishing the license Raj with LPG movement, in the year 1993, twelve new private sector banks were set up. An era of change entered the Indian Banking industry by infusing the use of technology that changed the face of banks in India and the role. Banks transformed their traditional work culture to an important service provider by performing functions like project appraisal and followup of assisted projects by institutions through various instruments, such as project monitoring and report of nominee directors on the Boards of directors of assisted units. The changed face of banks with new licenses opens up wide scope for the technological industries with a new horizon of growth for the banking industry. The second aspect is the expected new employment opportunity. Thus banks have transformed themselves from a traditional venue of depositor and generating savings for industry to the support system for the global economy.


As technology has become an inescapable part of most workplaces, it has become ever more important to understand its impact on employees. Using data from two surveys of U.S. workers, Noelle Chesley examines the effects of both personal and job-related technology use. She finds that increased technology use, especially when it extends work into personal life, is linked with higher levels of worker distress. However, it is also associated with gains in productivity, and personal technology use at work may help employees to manage work-related stress.


Social media platforms provide environments in which students from diverse backgrounds socialise, debate and share knowledge. At the same time, the value of such environments can be undermined by various forms of aggression and bigotry. Problems of online bullying, harassment and incivility present particular challenges for universities striving to foster an environment that is welcoming, inclusive and respectful. A range of official and unofficial online environments have become extensions of institutional culture, yet they cannot be regulated in the same manner as physical campus environments. This paper examines ways in which modes of racism, sexism and other forms of prejudice are propagated, normalised and sometimes challenged within universities' social media spaces. These groups show a marked difference in levels of debate and interpersonal engagement, such that in some cases, instances of racism, sexism and homophobia can lead to critical deliberation, while in others such bigotry goes unchecked.


This paper demonstrates the presence of significant territorial gaps in Italian subnational governments ability to generate revenue through local taxation. An exercise concerning three main local taxes shows that such fiscal gaps reflect primarily regional economies development, while differences in tax rates and tax evasion across the Country play a minor role. Within this framework, equalization causes substantial resources transfers in favour of those institutions with less fiscal resources endowment. In the second part of our paper we focus on such aspects, by describing the equalization mechanisms provided by some recent parliamentary bills that have recently become a hot topic in the Italian political debate and evaluating their potential distributive impact.


Background and relevance to radioactive waste management
International consensus confirms that placing radioactive wastes and spent nuclear fuel deep
underground in a geological repository is the generally preferred option for their long-term
management and disposal. This strategy provides a number of advantages compared to leaving it
on or near the Earth's surface. These advantages come about because, for a well chosen site, the
geosphere can provide:
• a physical barrier that can negate or buffer against the effects of surface dominated natural
disruptive processes such as deep weathering, glaciation, river and marine erosion or
flooding, asteroid/comet impact and earthquake shaking etc.
• long and slow groundwater return pathways from the facility to the biosphere along which
retardation, dilution and dispersion processes may operate to reduce radionuclide
concentration in the groundwater.
• a stable, and benign geochemical environment to maximise the longevity of the engineered
barriers such as the waste containers and backfill in the facility.
• a natural radiation shield around the wastes.
• a mechanically stable environment in which the facility can be constructed and will
afterwards be protected.
• an environment which reduces the likelihood of the repository being disturbed by inadvertent
human intrusion such as land use changes, construction projects, drilling, quarrying and
mining etc.
• protection against the effects of deliberate human activities such as vandalism, terrorism and
war etc.
However, safety considerations for storing and disposing of long-lived radioactive wastes must
take into account various scenarios that might affect the ability of the geosphere to provide the
functionality listed above. Therefore, in order to provide confidence in the ability of a repository
to perform within the deep geological setting at a particular site, a demonstration of geosphere
"stability" needs to be made. Stability is defined here to be the capacity of a geological and
hydrogeological system to minimise the impact of external influences on the repository
environment, or at least to account for them in a manner that would allow their impacts to be
evaluated and accounted for in any safety assessments.
A repository should be sited where the deep geosphere is a stable host in which the engineered
containment can continue to perform according to design and in which the surrounding
hydrogeological, geomechanical and geochemical environment will continue to operate as a
natural barrier to radionuclide movement towards the biosphere. However, over the long periods
of time during which long-lived radioactive wastes will pose a hazard, environmental change at
the surface has the potential to disrupt the stability of the geosphere and therefore the causes of
environmental change and their potential consequences need to be evaluated.
As noted above, environmental change can include processes such as deep weathering,
glaciation, river and marine erosion. It can also lead to changes in groundwater boundary
conditions through alternating recharge/discharge relationships. One of the key drivers for
environmental change is climate variability. The question then arises, how can geosphere stability be assessed with respect to changes in climate? Key issues raised in connection with
this are:
• What evidence is there that 'going underground' eliminates the extreme conditions that
storage on the surface would be subjected to in the long term?
• How can the additional stability and safety of the deep geosphere be demonstrated with
evidence from the natural system?
As a corollary to this, the capacity of repository sites deep underground in stable rock masses to
mitigate potential impacts of future climate change on groundwater conditions therefore needs to
be tested and demonstrated. To date, generic scenarios for groundwater evolution relating to
climate change are currently weakly constrained by data and process understanding. Hence, the
possibility of site-specific changes of groundwater conditions in the future can only be assessed
and demonstrated by studying groundwater evolution in the past. Stability of groundwater
conditions in the past is an indication of future stability, though both the climatic and geological
contexts must be taken into account in making such an assertion.


The uptake of choline by L5178Y lymphoblasts occurs by a carrier mechanism and is an active process. Transport of nitrogen mustard and its hydrolyzed derivative is mediated by this same carrier. This finding is an example of drug transport by a carrier whose primary function is transport of a naturally occurring substrate.


OBJECT
Hemodynamic instability may complicate carotid angioplasty and stenting in up to 40% of patients. The authors have previously demonstrated that primary self-expanding stent placement alone can gradually dilate severely stenosed carotid arteries without the use of balloons. The authors hypothesized that eliminating the balloon would reduce carotid baroreceptor stimulation, thereby decreasing the incidence of hemodynamic instability.

METHODS
Ninety-seven high surgical risk patients with symptomatic, severely stenosed carotid arteries were treated with the intention of using a self-expanding stent alone. Seventy-seven arteries (79%) were treated with stenting alone, and 20 required angioplasty (21%).

RESULTS
Intraprocedural bradycardia (heart rate < 60 bpm) developed in 29 patients (38%) and hypotension (systolic blood pressure < 90 mm Hg) occurred in 1 patient (1%) treated with stenting alone. Fourteen patients (70%) who underwent angioplasty and stenting had bradycardia, and hypotension developed in 4 (20%). Atropine, glycopyrrolate, or vasopressors were required in 8% of patients who received stenting alone, compared to 30% of patients who underwent angioplasty. In the first 24 hours after treatment, hypotension or bradycardia developed in 25 patients (32%) who had undergone stent placement alone, and in 15 patients (75%) after stent placement and balloon angioplasty. There was no difference in the occurrence of intra- or postprocedural hypertension (systolic blood pressure > 160 mm Hg) between patients treated with stenting alone or stenting and balloons. Factors independently associated with hemodynamic depression included baseline heart rate and balloon use.

CONCLUSIONS
Hemodynamic instability during and after carotid artery stenting was observed more frequently when balloon angioplasty was required than when stent placement was performed without concurrent balloon angioplasty.


Constructed slopes are often amended with compost in order to reduce erosion and improve vegetation establishment. These composts can contain soluble nutrients which may become a source of pollution to nearby water bodies. This study examined annual sediment and nutrient losses in surface runoff from nine potential types of compost treatments. These included treatments that tested differences between two types of compost (mature and immature) as well as various methods of compost application, including surface blankets and incorporation. Over an entire rain season, there were no significant differences in sediment and nutrient (NO3−, NH4+ and P) losses between the two compost types when they were applied as surface blankets. In treatments where a compost blanket was applied over the top of compost tilled into the soil there was a significant reduction in sediment loss compared to treatments where compost was just tilled into the soil, without a blanket overlay. This treatment reduced sediment loss to a level that was comparable to vegetated treatments. Although this treatment had twice the amount of compost as the treatments with just a surface blanket of compost, it lost less than a fourth as much nitrate in its runoff over the year as either compost type when they were applied as a blanket over bare soil. The greatest sediment loss came from treatments in which compost was tilled into the soil with no additional compost surface blanket. Effects of different treatments were confounded by a gradient in slope hydrology that resulted in a relationship between runoff volume and plot position along the slope. Our statistical analysis took this into account and the data presented represent our attempt to control for this nuisance variable. Our findings suggest that compost can be used as a soil amendment and as an erosion control measure on constructed slopes at a minimal risk of nutrient loss if it is done in the proper manner. We recommend that compost be incorporated into the soil to facilitate greater infiltration and that a blanket of compost or woody mulch be placed over the soil to provide surface erosion protection.


Background There is a need for a patient-reported outcome (PRO) questionnaire to evaluate patients with proximal hamstring tendinopathy (PHT). Objective To develop a PRO questionnaire based on VISA questionnaire forms for patients with PHT. Methods Item generation, item reduction, item scaling and evaluation of the psychometric properties were used to develop a questionnaire to assess the severity of symptoms, function and ability to play sports in patients with PHT and healthy subjects. The final version, named Victorian Institute of Sport Assessment-Proximal Hamstring Tendons (VISA-H), consisted of eight questions that measured the domains of pain, function and sporting activity. The psychometric properties of a questionnaire were estimated in a population of non-surgical (n=20) and surgical (n=10) patients, as well as in healthy subjects (n=30). Results The VISA-H questionnaire displayed a high degree of internal consistency, with a Cronbach α of 0.84. (The test–retest reliability was high for all groups of participants with an intraclass correlation coefficient ranging from 0.90 to 0.95.) The VISA-H exhibited a high correlation with the Nirschl phase rating scale (r ranging from −0.75 to −0.89) and a generic tendon grading system proposed by Curwin and Stanish (r ranging from −0.70 to −0.88). Also, the responsiveness was higher for the VISA-H questionnaire with an area under the curve of 0.90 and a minimum clinically important difference of 22 points. Conclusions The VISA-H is a PRO questionnaire with high psychometric properties for measuring pain, function and sporting activity in patients with PHT.


Functional and structural aspects of intercellular interactions are considered. Chemical substances are universal mediators of intercellular interactions. Electrical and mechanical interactions are also involved in cell-cell cooperation. Functional peculiarities of the two principal types of intercellular interactions-ligand-receptor interactions and interactions based on permeable contacts-are compared. Examples of basic tissue processes are given (such as the mechanisms of embryonic induction and differentiation, regulation of cell proliferation, temporal and spatial regulation of the activity of differentiated cells, interactions between excitable cells) to illustrate the notion that the types of intercellular interactions are mutually complementary and fulfill different functions. Ligand-receptor interactions predominantly provide signal functions and ensure intertissue interactions, while the interactions based on permeable contacts mainly fulfill intratissue coordination relying on positional information and the exchange of energy and matter.


Two-stage alkaline/copper 2,2′-bipyridine-catalyzed alkaline hydrogen peroxide (Cu-AHP) pretreatment is an effective strategy for improving the enzymatic digestibility of hybrid poplar. To reduce the chemical inputs and processing costs associated with this process, we investigated the effect of increasing the temperature for both the alkaline pre-extraction and the Cu-AHP pretreatment stages. The results indicate that increasing the alkaline pre-extraction and the Cu-AHP pretreatment temperatures from 30 to 120 and 80 °C, respectively, allowed us to reduce both the pretreatment time of the Cu-AHP stage and the chemical loadings. Incubating alkaline pre-extracted hybrid poplar for 12 h with 10% NaOH (w/w biomass), 8% hydrogen peroxide (w/w biomass), and a Cu2+ and 2,2′-bipyridine (bpy) concentration of 1 mM yielded monomeric sugar yields of approximately 77% glucose and 66% xylose (based on the initial sugar composition) following enzymatic hydrolysis. Technoeconomic analysis (TEA) indicates that these ch...


Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.


S CJ M M A R Y. Setting: First grade students in primary schools in the city of Barcelona, Spain. Objective: To estimate the prevalence of tuberculin reaction and sources of infection; to analyse trends in comparison with previous data. Design: Tuberculin screening of first grade schoolchildren (1985 birth cohort) was undertaken in 1991-92 using 2 TU of PPD RT23. Results: The prevalence of reactors among the 12 007 children tested from the 1985 cohort was 0.87%, varying among districts between 0.13% and 3.03%. Follow-up of positive tests was completed for 75 children, which led to the identification of 6 cases of previously unknown clinical tuberculosis among these children, while for 14 infected children index cases were found, one of whom was a confirmed HIV-infected IVDU. Conclusion: The comparison of results with data from previous studies suggests that tuberculosis infection among schoolchildren in Barcelona may not be declining as in previous years, especially in areas such as the inner city, where poverty combines with HIV infection and with increasing migration from countries with a higher tuberculosis prevalence.


Herein, freestanding wurtzite aluminum nitride (AlN) bulk single crystals (BSCs) were massively grown on a tungsten substrate using a two-heater physical vapor transport (th-PVT) method. The growth was along the c-axis of the hexagonal lattice with the crystal scales in the millimeter level. Cathodoluminescence (CL) measurement was performed on the AlN BSCs. The CL spectra showed both near band edge emission at 6.02 eV and defect-related emissions at around 4.60 eV (VAl) and 3.30 eV (VAl–O complex). Moreover, an electroluminescence (EL) device with a sandwich structure of Au–AlN–W was fabricated and characterized. This EL device demonstrated an asymmetric current–voltage curve and white light luminescence with high color quality under high bias. They were attributed to different non-ohmic contacts at the metal–semiconductor interfaces and intrinsic defect-related energy states. This study aims at the pioneering exploration of the application of freestanding AlN BSCs in optoelectronic devices.


Motivated by the study of pattern avoidance in the context of permutations and ordered partitions, we consider the enumeration of weak-ordering chains obtained as leaves of certain restricted rooted trees. A tree of order $n$ is generated by inserting a new variable into each node at every step. A node becomes a leaf either after $n$ steps or when a certain stopping condition is met. In this paper we focus on conditions of size 2 ($x=y$, $x<y$, or $x\le y$) and several conditions of size 3. Some of the cases considered here lead to the study of descent statistics of certain `almost' pattern-avoiding permutations.


A temperature-sensitive Escherichia coli mutant defective for the ability to utilize L-asparagine as a sole nitrogen source was isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutation (asu) produces two distinct phenotypic effects. Mutant strains grow poorly at high temperature on minimal plates containing asparagine as the sole nitrogen source; this effect is greatly exacerbated by the presence of methionine. Mutant strains utilize L-asparagine as a nitrogen source three to four times more efficiently at permissive temperatures than the wild-type strains. The mutation maps at 32.4 min on the E. coli chromosome, within the E. coli cotransduction gap. Mutant strains produce normal amounts of thermo-stable L-asparaginase I activity. The mutation therefore affects a component of the asparagine utilization system other than the catabolism of asparagine within the cell; it probably affects asparagine uptake.


OBJECTIVE
To evaluate the performance of Zika virus(ZIKV)disease prevention and control.

METHODS
Descriptive epidemiological analysis was conducted on the clinical manifestations, laboratory detection results and disease progression of the third imported ZIKV disease case in the mainland of China.

RESULTS
On 19 February 2016, a ZIKV disease case was confirmed in Yiwu, Zhejiang province, which was the third imported case of ZIKV disease confirmed by China CDC laboratory and expert consulting. The patient just had a travel to Fiji and Samoa and had mosquito bite history in Samoa. The patient was hospitalized on 16 February after the onset on 14 February and the eruption on 15 February. The body temperature of the patient became normal on 17 February, the rash disappeared on 19 February and the conjunctivitis resolved on 20 February. The positive detection of the viral nucleic acid in blood was only for 3 consecutive days, and the viral nucleic acid could be detected in urine even after negative detection in blood for 4 days.

CONCLUSION
The symptoms of the patient were typical. ZIKV can be detected by using blood sample in early phase, but after body temperature become normal, the virus can be detected in urine.


We have mapped protein conformational space from two to seven residue lengths by employing multidimensional scaling on a data matrix composed of pair-wise angular distances for multiple phi-Psi values collected from high-resolution protein structures. The resulting global maps show clustering of peptide conformations that reveals a dramatic reduction of conformational space as sampled by experimentally observed peptides. Each map can be viewed as a higher order phi-Psi plot defining regions of space that are conformationally allowed.


This comparative study of the constitutional jurisprudence of three East Asian jurisdictions investigates how the rulings of the Constitutional Court of Taiwan, the Constitutional Court of Korea and the Hong Kong Court of Final Appeal have converged. The unique political contexts of all three jurisdictions have led to strong courts using the structured proportionality doctrine and innovative constitutional remedies to address human rights issues. Hong Kong, Taiwan, and South Korea have the only courts in Asia that regularly use a structured four-stage Proportionality Analysis to invalidate laws, and routinely apply innovative constitutional remedies such as Suspension Orders and Remedial Interpretation to rectify constitutionally flawed legislation. This volume explores how judges in these areas are affected by politics within their different constitutional systems. The latest developments in Asian constitutional law are covered, with detailed analysis of key cases.


One of the unique features of the REPORT procedure is the Compute Block. Unlike most other SAS ® procedures, PROC REPORT has the ability to modify values within a column, to insert lines of text into the report, to create columns, and to control the content of a column. Through compute blocks it is possible to use a number of SAS language elements, many of which can otherwise only be used in the DATA step. While powerful, the compute block can also be complex and potentially confusing. This tutorial introduces basic compute block concepts, statements, and usages. It discusses a few of the issues that tend to cause folks consternation when first learning how to use the compute block in PROC REPORT.


The Korean Neutrino Observatory (KNO) is proposed as a next generation underground neutrino detector in Korea. The detector is a 260 kiloton water Cherenkov detector and can serve as the second detector of Hyper-Kamiokande experiment. By detecting J- PARC neutrino beam in these two detectors in Korea and Japan at the same time, the measurement of neutrino oscillation
parameters such as leptonic CP phase and the neutrino mass ordering is expected to be improved. Physics sensitivity studies are performed with improved handling of systematic uncertainties compared to the previous study. We present preliminary results on physics sensitivities in various configurations of Hyper-Kamiokande experiment including the KNO configuration.


Breathlessness is a common and distressing symptom in both malignant and non-malignant conditions. Both pharmacological and non-pharmacological strategies are necessary to minimise symptom burden and distress. Assessing the individual's needs and clarifying the goals of treatment is an important first step in determining an effective treatment plan. Although the evidence supporting the use of some of these therapies is variable, there is an increasing evidence base to inform clinical decision making and treatment plans. Pharmacotherapy with opioids is a common and effective strategy for managing breathlessness, yet requires judicious titration and management. The adverse effects of opioid therapy, including constipation and drowsiness, can be anticipated and managed with adjunctive therapies. The use of oxygen in people who are hypoxaemic is supported, but is of limited value in people who are not hypoxaemic. Individualised strategies and advance care planning is important to avoid unnecessary hospitalisations and futile treatments at the end of life. There is a clear mismatch between the prevalence and burden of this problem and data to inform evidence-based guidelines. Refractory breathlessness is a fertile area for ongoing research and requires increased attention to address the burden of this highly prevalent symptom.


Unbundled power quality service is paid much attention under the circumstances of deregulation and diversification of needs of cus- tomers for quality and price of electric power. Moreover, distributed generators will be intro- duced to distribution system more and more, and reverse flow of active power has possibility to cause new problems in the distribution system. FRIENDS (Flexible, Reliable and Intelligent Elec- trical eNergy Delivery System) is proposed as one of promising distribution system for such require- ments. One of the most important characteristics of FRIENDS is that QCC (Quality Cbntrol Center) is installed very closely to customers in order to supply unbundled power quality service. In this paper, dc loop type QCC is proposed as one of the configurations of QCCs. Moreover the circuit configurations, the control schemes, and the simulation results of two types of PFCs (Power Factor Correctors) which are used in this system are presented.


In patients who need endodontic re-treatment, and where the prognosis for surgical or non-surgical re-treatment is poor or treatment may be risky, one alternative is to opt for extraction of the affected tooth and replacement by an implant. However treatment by intentional reimplantation (IR) is also a possibility. The object of the present study was to present a case of a patient aged 71 years who needed endodontic re-treatment, where IR treatment was selected. The patient reported spontaneous pain which disappeared completely with the use of analgesics. This tooth had previously been treated endodontically around 1 year earlier, and no pain was reported in the first two months after treatment.Nonetheless, about 3 months before the present consultation, intensity of the symptoms had increased with a sensation of pressure in the apical-coronal direction. Cone-beam computerised tomography (CBCT) showed a periapical lesion in tooth 3.7. Based on the clinical and imaging examinations, acute apical periodontitis was diagnosed in tooth 3.7.The tooth was treated by IR. It was carefully extracted and inspected for cracks or perforations. It was treated under the microscope with root resection, and then retrograde obturation was carried out with bioceramic material. The tooth was then repositioned in its alveolus. It was immobilised for 15 days, after which the patient could return gradually to normal masticatory function. In the 6 months check-up the patient presented no pain or sensitivity to percussion. No root resorption or periapical radiolucency was observed in the periapical X-ray. We conclude that IR is an alternative to extraction followed or not by prosthetic treatment, for patients who need endodontic re-treatment. The treatment presents good levels of success, and of acceptance by the patient.


Letters and meanings is a tool for achieving an A.1 level in Arabic (according to the Common European Framework). Its main goal is to familiarize students with reading and writing the Arabic language. It is aimed at English-speaking students in a learning environment with an instructor. The independent learner, however, will also find recommendations and strategies for study as well as diverse materials and resources which will allow him or her to get acquainted with the new system of written signs and sounds which he or she hopes to learn.
Letters and meanings is presented like an Arabic book, to be read from right to left. If you choose to print it, be careful and bind it to the right in order to use it properly. The book begins with an introductory and theoretical unit about the Arabic language. It is divided into eight teaching units, plus one review unit, and concludes with an answer key to the exercises, classroom vocabulary, some brief notes on Arabic calligraphy, and two glossaries. All of this is accompanied by downloadable mp3 audio files.


Traditional event detection classifies a word or a phrase in a given sentence for a set of prede- fined event types. The limitation of such pre- defined set is that it prevents the adaptation of the event detection models to new event types. We study a novel formulation of event detec- tion that describes types via several keywords to match the contexts in documents. This fa- cilitates the operation of the models to new types. We introduce a novel feature-based attention mechanism for convolutional neural networks for event detection in the new for- mulation. Our extensive experiments demon- strate the benefits of the new formulation for new type extension for event detection as well as the proposed attention mechanism for this problem


Vast research indicates the importance of personality traits in predicting different types of risk behaviour in adolescents. In the last couple of years, several personality questionnaires have been successful in predicting risk behaviour in adolescents. The majority of these questionnaires have not been adapted in the Croatian language. The goal of this survey is to show Croatian translation of the Severity Indices of Personality Problems (SIPP-118) and the short version of the Personality Inventory for DSM-5 (PID-5). Dimensional Assessment of Personality Questionnaire (DAPQ) has been used to assess the convergent validity of PID-5 questionnaire, while Self-reported Delinquency and Risk Behaviours Questionnaire (SRDP) has been used for the assessment of the predictive PSIHOLOGIJSKE TEME, 29 (2020), 2, 269-290 290 validity of PID-5 and SIPP-118. The survey was conducted on 497 high school and vocational students in Osijek, Beli Manastir, Đakovo and Donji Miholjac. The results of the confirmatory factor structure of SIPP-118 questionnaire did not confirm the anticipated factor structure. Five-factor structure PID-5 has been declared as the best model, but the scales are highly interrelated, which diminishes the divergent validity of the questionnaire. The results show that personality traits and personality functioning scales are moderately related to the tendency to risk and socially unacceptable behaviour. The hierarchical regression analysis has shown that a larger part of the variance in risk behaviour can be explained using DAPQ questionnaire than using PID-5. Considering the results of this survey, caution is advised in using translated questionnaires.


As a result of the continuously increasing amount of important data, the demand for information security increases daily. Steganographic techniques can play a considerable role in solving this issue, since they can hide the necessary data. Generally, audio and image files have been utilized as hiding media in this area. However, because of their limited capacity, these media limit the amount of hidden information. On the other hand, the capacity limit can be exceeded by applying steganography on video files. There are few studies on video steganography in the literature. In this study, a steganographic library, which is independent of medium and method, was developed for hiding information in audio, image, and video files by using various methods. Furthermore, distinctly from other studies, the lattice approach was proposed for this issue. In this approach, security was increased by using the image and audio domain of video together in the hiding process. In addition, we were able to hide the real-time data in a video taken from a webcam. Thus, the size of the produced video file could be set, according to the size of the secret file, with this model. Meanwhile, the possibility of detecting the existence of steganography by comparing to the original video was limited. The success of the hiding process was also evaluated with various steganalyses and noise measurement methods, and the results are presented and discussed in the relevant sections.


LEDs, of late, have received attention as the next generation lighting system for enhanced luminous efficiency and higher lifespan. However, the thermal management of the LEDs is the crucial parameter to be countered for global acceptance as a revolutionary illumination source. This paper reports the experimental investigation of natural convective heat transfer of high power LED COBs using MWCNT and MWCNT-CuO nanofluids mixed with de-ionized water. The study uses MWCNT based nanofluids as a route to enhance the heat transfer of high power LEDs by the passive cooling technique. This study presents an innovative cooling device integrated with numerous fluid pockets, called the HSFP, to achieve the enhanced thermal performance of heat sinks for applications in high intensity LED lights. Nanofluids of various concentrations were formulated and their heat transfer performance evaluated using a series of experiments and compared with liquid cooling and a conventional heat sink. The experimental finding reveals 20– 30% lowered thermal resistance using the new HSFP (nanofluids). Thus, the HSFP found to effectively dissipates the heat in high-power LED COBs using nanofluids as the cooling medium compared to the conventional heat sink.


BackgroundLong-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The objective is to determine the effect of AED on vitamin D levels and bone density in ambulatory patients and to compare the effects of enzyme-inducing and -noninducing AED and of single vs multiple therapy on bone density. MethodsA cross-sectional evaluation was conducted of 71 patients (42 adults and 29 children/adolescents) on anticonvulsant therapy for at least 6 months who presented to neurologists at a tertiary referral center. Bone mineral density (BMD) as well as serum 25 hydroxy–vitamin D (25-OHD) levels were measured. A detailed questionnaire assessing calcium intake as well as previous and current intake of antiepileptic medications was administered to all patients. Results Over 50% of adults and children/adolescents had low 25-OHD levels, but this finding did not correlate with BMD. Antiepileptic therapy decreased BMD in adults. Generalized seizures, duration of epilepsy, and polypharmacy were significant determinants of BMD, more so at skeletal sites enriched in cortical bone. Subjects on enzyme-inducing drugs such as phenytoin, phenobarbital, carbamazepine, and primidone tended to have lower BMD than those on noninducers such as valproic acid, lamotrigine, clonazepam, gabapentin, topamirate, and ethosuximide. ConclusionEpilepsy and its therapy, including the newer drugs, are risk factors for low bone density, irrespective of vitamin D levels. Skeletal monitoring with the institution of appropriate therapy is indicated in patients on chronic antiepileptic therapy.


Purpose: To review the clinical features, complications, and treatment of Waldenström's macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. Methods: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. Results: The clinical manifestations associated with Waldenström's macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. Conclusion: Waldenström's macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients' survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent. J Clin Oncol 18:214-226. © 2000 by American Society of Clinical Oncology.


Pathological changes of the vasculature are characterized by changes in Ca 21 handling and alterations in gene expression. In neurons and other cell types, [Ca ]i often drives changes in gene expression. However, the relationship between Ca 21 signaling and gene expression in vascular smooth muscle is not well understood. This study examines the ability of Ca influx through voltage-dependent, L-type Ca 21 channels (VDCCs) and Ca 21 release through ryanodine receptors (RyRs) to activate the transcription factor, cAMP-responsive element binding protein (CREB), and increase c-fos levels in intact cerebral arteries. Membrane depolarization increased the fraction of nuclei staining for phosphorylated CREB (P-CREB) and levels of cfosmRNA in intact mouse cerebral arteries. Ryanodine, which inhibits RyRs, increased P-CREB staining and cfos levels. Forskolin, an activator of adenylyl cyclase, and sodium nitroprusside, an NO donor, increased P-CREB and cfos levels. Nisoldipine, an inhibitor of VDCCs, reversed the effects of depolarization and ryanodine on P-CREB and cfos levels, but not the effects of forskolin or sodium nitroprusside. Inhibition of Ca /calmodulin-dependent protein kinase (CaM kinase) blocked increases in P-CREB and c-fos levels seen with membrane depolarization, suggesting that CaM kinase has an important role in the pathway leading from Ca influx to CREB-mediated changes in cfos levels. Our data suggest that membrane depolarization increases [Ca ]i through activation of VDCCs, leading to increased P-CREB and cfos, and that RyRs have a profound effect on this pathway by indirectly regulating Ca 21 entry through VDCCs. These results provide the first evidence of Ca regulation of CREB and c-fos in arterial smooth muscle. (Circ Res. 2000;86:760-767.)


From the perspectives of regulation and convergence, several debates on the industrial definition of smart TV service in Korean broadcasting and communications market have been in progress. The most heated controversy mainly depends on whether smart TV is controlled under the broadcasting regulations or under the communications regulations. This Korean specific problem is summarized in regulation fairness or asymmetric regulation between smart TV and IPTV operators. Although both operators utilize very similar technology and offer same business model, smart TV operators are only unfettered without any legal restriction. This would be an intrinsic cause prohibiting fair competition in the new converging market. Currently we confront the matter of asymmetric regulation between smart TV and others including IPTV or ISP. The purpose of this study is to provide the strategic, regulatory guidance and theoretical definitions on smart TV service, as one of converging services, based on a qualitative approach through the Q methodology. This Q study identified three issues including 'Net neutrality', 'Regulation fairness', and 'New media and new market,' and proposed desirable promotion plans regarding those issues. Consequently, the study draws lessons learned through a Korean smart TV case and provides directions to strategic-policy studies for future emergent converging services.


The enrollment of adolescents with cancer in clinical trials is much lower than that of younger pediatric patients. For adolescents with "adult-type" cancers, lack of access to relevant trials is cited as one of the reasons for this discrepancy. Adolescents are generally not eligible for enrollment in adult oncology trials, and initial pediatric trials for many drugs are conducted years later, often after the drug is approved. As a result, accrual of adolescents to these trials may be slow due to off-label use, prospectively collected safety and efficacy data are lacking at the time of initial approval, and, most importantly, these adolescents have delayed access to effective therapies. To facilitate earlier access to investigational and approved drugs for adolescent patients with cancer, and because drug exposure is most often similar in adolescents and adults, we recommend the inclusion of adolescents (ages 12–17) in disease- and target-appropriate adult oncology trials. This approach requires careful monitoring for any differential safety signals, appropriate pharmacokinetic evaluations, and ensuring that ethical requirements are met. Inclusion of adolescents in adult oncology trials will require the cooperation of investigators, cooperative groups, industry, institutional review boards, and regulatory agencies to overcome real and perceived barriers. Clin Cancer Res; 23(1); 9–12. ©2016 AACR.


Mammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-activated, Na+ selective channel, in the ligand-bound and apo states. The apo structure captures the closed conformation, while the ligand-bound form features the channel in both open and closed conformations. Combined with functional analysis, these structures provide insights into the mechanism of PI(3,5)P2-regulated gating of TPC2, which is distinct from that of TPC1. Specifically, the endolysosome-specific PI(3,5)P2 binds at the first 6-TM and activates the channel – independently of the membrane potential – by inducing a structural change at the pore-lining inner helix (IS6), which forms a continuous helix in the open state but breaks into two segments at Gly317 in the closed state. Additionally, structural comparison to the voltage-dependent TPC1 structure allowed us to identify Ile551 as being responsible for the loss of voltage dependence in TPC2.