The traditional concept of national and international security in essence stay away from war between and avert offensive by other states have, necessarily, been outmoded in recent time. In the post-cold war era "human security" has enormously become significant, mainly since September th 200. The need of human security has become the turning point in the international politics, and human security issues have been accepted both by policy makers and international institutions. A further incorporated approach to studying this field is obligatory to attain the preferred outcome of combined security, i.e from the individual to international level.


In this paper, the effect of Equal Channel Angular Pressing (ECAP) process on the structure and mechanical properties of AM30 magnesium alloy was studied. The results showed a considerable effect of ECAP process on creating an ultrafine grain size structure. Scanning Electron Microscope indicated that the grain size dropped from 20.4 μm in the extruded form to 7.2 μm in the first pass and 3.9 μm in fourth pass. The fourth pass presented higher ductility and lower yield stress in comparison with the extruded case. This behavior can be explained based on higher rate of texture softening versus the effects of the grain refinement on strength. The hardness test on the samples cross-section showed an increase in hardness and a uniform strain distribution at higher ECAP passes.


BACKGROUND
The expansion of Aedes aegypti (Diptera: Culicidae) population has increased the number of cases of arboviruses, in part due to the inefficiency and toxicity of the chemical control methods available to control this vector. We synthesized 19 chalcone derivatives and examined their activity against Ae. aegypti larvae in order to select larvicidal compounds that are non-toxic to other organisms.

RESULTS
Seven chalcone derivatives (3a, 3e, 3f, 6a, 6c, 6d, and 6f) had LC50 values lower than 100 mg mL-1 at 24 h post-treatment, which is the dose that the World Health Organization recommends for the selection of promising larvicides. The type of substituent added to (E)-1,3-diphenylprop-2-en-1-one (3a) markedly affected the larvicidal activity. Addition of chlorine, bromine and methoxy groups to the aromatic rings reduced the larvicidal activity, while replacement of the B-ring (phenyl) by a furan ring significantly increased the larvicidal activity. The furan-chalcone (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) killed Ae. aegypti larvae (LC50 = 6.66 mg mL-1 ; LC90 = 9.97 mg mL-1 ) more effectively than the non-substituted chalcone (3a) (LC50 = 14.43 mg mL-1 ; LC90 = 20.96 mg mL-1 ), and was not toxic to the insect Galleria mellonella, to the protozoan Tetrahymena pyriformis, and to the algae Chorella vulgaris.

CONCLUSIONS
The substitution pattern of chalcones influenced their larvicidal activity. In the set of compounds tested, (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) was the most effective larvicide against Ae. aegypti, with no clear signs of toxicity to other animal models. Its mechanism of action and effectiveness under field conditions remain to be determined. This article is protected by copyright. All rights reserved.


We consider the problem of real-time animation of a cartoon character which is represented by a skeleton implicit surface. If the character's motions permit a constant topology for the skin, it is possible to reduce the problem of computing an approximation of the implicit surface to solve only one scalar equation per surface point for a fixed number of surface points; these surface points define the shape of a triangle mesh with constant topology. We present the algorithm, and demonstrate its working in a real-time model of walking cartoon legs.


Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.


In this paper, we propose a grid-connected photovoltaic power system including batteries in order to provide prescribed reactive and real powers to the grid. According to the stochastic nature of the photovoltaic power, the main feature of the proposed system is to erase power fluctuations by designing a dedicated local control system. With batteries, the whole system is able to smooth the PV power and provides a power reference, which is required by the grid operator. Therefore, the photovoltaic systems can be integrated more efficiently in the grid system and participate to the grid stability. An equivalent continuous dynamic model and control design of the studied power system are proposed in this paper. Simulation results are given to validate the feasibility of the proposed system.


Grid connected inverters, especially those used in DG (Distributed Generation) system, are expected with decoupled and flexible power control ability. Many existing power control methods are based on synchronous reference frame transformation, which requires the phase angle information provided by Phase-Locked Loop (PLL). This creates additional drawbacks of the system and makes the system complex. This paper presents a controller for single-phase grid connected inverter system with LCL filter in stationary reference frame. And PLL is avoided. Compared with traditional power control scheme for single phase grid-connected inverter controller, this control scheme has faster response, higher reliability and decoupled real and reactive power control ability. Moreover, the proposed controller has good robustness under different distorted grid conditions. Since the controller is totally implemented in stationary reference frame, the control algorithm comes to be simpler and easier. The designed current controller, combining the active damping technique, helps restrain the high resonant peak value. Compared with traditional PI based current controller, the designed current controller, which is based on the Proportional & Resonant (PR) controller, provides the system with high gain in wide range of frequency to track given reference value fast and output excellent grid current with low THD.


Machine-learning excels in many areas with well-defined goals. However, a clear goal is usually not available in art forms, such as photography. The success of a photograph is measured by its aesthetic value, a very subjective concept. This adds to the challenge for a machine learning approach.
We introduce Creatism, a deep-learning system for artistic content creation. In our system, we break down aesthetics into multiple aspects, each can be learned individually from a shared dataset of professional examples. Each aspect corresponds to an image operation that can be optimized efficiently. A novel editing tool, dramatic mask, is introduced as one operation that improves dramatic lighting for a photo. Our training does not require a dataset with before/after image pairs, or any additional labels to indicate different aspects in aesthetics.
Using our system, we mimic the workflow of a landscape photographer, from framing for the best composition to carrying out various post-processing operations. The environment for our virtual photographer is simulated by a collection of panorama images from Google Street View. We design a "Turing-test"-like experiment to objectively measure quality of its creations, where professional photographers rate a mixture of photographs from different sources blindly. Experiments show that a portion of our robot's creation can be confused with professional work.


Much research attention has been devoted to community context and health. Communities are often defined as residential spaces, such as neighborhoods, or as social groupings, such as caste in India. Using data from a group of tea estates in South India, we attempt to address important methodological challenges in the identification of neighborhood effects on child health. We find significant neighborhood effects for weight for age at age one, including a protective role for community-level women's education, but none for birth weight. In contrast to the usual pattern in rural India, caste disparities in child health are also eliminated in this setting.


This paper examines to what extent household leverage—as measured by the debt-to-income (DTI) ratio—predicts delinquency in Peru's consumer credit market. A model is estimated to assess the relation between delinquency and the DTI ratio. The initial and current DTI ratios are assessed as delinquency predictors. The results confirm that the current DTI ratio is effective for predicting delinquency. This evidence supports its use in financial regulation to improve household credit risk assessment and control.


In order to test the concept of "sleep learning", cats were exposed to habituation treatment of auditory stimuli during different stages of the sleep-waking cycle. While it was possible to demonstrate that habituation to an auditory stimulus can take place in paradoxical sleep (PS) and slow-wave sleep (SWS) as well as during periods of wakefulness, it was not always possible to demonstrate a transfer of habituation from the training period to other periods. A complete transfer of habituation occurred between the two sleep periods (PS and SWS); a partial transfer of habituation occurred between the waking period and both of the two sleep stages (PS and SWS), but only a minimal transfer of habituation was found between any one of the sleep stages and the waking period. When the cats were able to transfer the habituation, they also were able to discriminate between the habituating tone and a novel tone. The findings that only minimal transfer of habituation could occur between each of the sleep stages and the waking period do not lend support to the concept of "sleep learning".


Two very different models of product innovation are postulated and tested. The conservative model assumes that innovation is performed reluctantly, mainly in response to serious challenges. It therefore predicts that innovation will correlate positively with environmental, information processing, structural and decision making variables that represent, or help to recognize and cope with these challenges. In contrast, the entrepreneurial model supposes that innovation is always aggressively pursued and will be very high unless decision makers are warned to slow down. Thus negative correlations are predicted between innovation and the variables that can provide such warning. Correlational and curvilinear regression analyses revealed that each model was supported by conservative and entrepreneurial sub‐samples, respectively, in a diverse sample of 52 Canadian firms.


In recent years there has been significant progress in algorithms and methods for inducing Bayesian networks from data. However, in complex data analysis problems, we need to go beyond being satisfied with inducing networks with high scores. We need to provide confidence measures on features of these networks: Is the existence of an edge between two nodes warranted? Is the Markov blanket of a given node robust? Can we say something about the ordering of the variables? We should be able to address these questions, even when the amount of data is not enough to induce a high scoring network. In this paper we propose Efron's Bootstrap as a computationally efficient approach for answering these questions. In addition, we propose to use these confidence measures to induce better structures from the data, and to detect the presence of latent variables.


OBJECTIVE
Primary carcinoma of the fallopian tube (PCFT) is a rare malignancy comprising 1% of genital tract cancers. We sought to compare survival trends between PCFT and ovarian carcinoma (OC) patients (pts) in a matched, case-control comparison.

MATERIALS AND METHODS
Patients with PCFT were identified from five academic centers. Two OC controls were identified for each PCFT pt based on age, stage, and residual disease. All pts were surgically staged and treated with platinum based chemotherapy (CT) if indicated. PFS and OS were then compared with Kaplan-Meier analysis.

RESULTS
96 PCFT cases and 189 OC controls were identified. 50 early stage PCFT were matched with 97 OC pts. The most common CT regimen was carboplatinum and paclitaxel in 84 and 86% respectively. Median follow-up was 57 and 42 months for the PCFT and OC groups and 5-year overall survival (OS) differed at 95% and 76% (p=0.02). 46 Stage III/IV PCFT pts were matched with 92 OC controls. 88.5% were optimally debulked. Median follow-up was 33 and 35 months for PCFT and OC pts and 3-year overall survival was 59% for both groups.

CONCLUSIONS
This is the first study to compare outcomes for PCFT and OC in a matched, case-control comparison. Our study demonstrates that, for advanced stage PCFT, a similar survival outcome is obtained compared to OC patients. This should reassure clinicians that treatment of PCFT should mirror that of OC and that PCFT should be included in clinical trials.


Signs of Safety (SoS) is a comprehensive assessment framework (AF) used in some form in most English children's service departments as well as in many other countries. The Framework for the Assessment of Children in Need and their Families (AF) was introduced nearly twenty years ago to address identified failures to adopt a holistic approach to assessments of families where there were concerns that children were in need of protection or support. The AF is not only a statutory requirement in England but it has influenced the development of approaches to assessment globally. An evaluation of SoS in pilot local authorities in England provided opportunities to examine the extent to which the two frameworks were being used together. Findings from interviews, case record analysis and a survey indicate that while recording processes were aligned with the AF, it was not central to many of the assessments conducted and it proved difficult to detect its influence on their content. It appears timely to examine the extent to which the AF is used across England, to assess its relevance to current practice and the extent to which frameworks such as SoS have supplemented or replaced it.


Abstract The intranasal distribution of aerosol from a metered dose inhaler has been assessed using a radiotracer technique. Inhalers were prepared by adding 99Tcm-labelled Teflon particles (simulating the drug particles) to chlorofluorocarbon propellants, and scans of the head (and chest) taken with a gamma camera. Ten healthy subjects (age range 19–29 years) each performed two radioaerosol studies with the inhaler held in two different ways: either in a single position (vial pointing upwards) or in two positions (vial pointing upwards and then tilted by 30° in the sagittal plane). The vast majority of the dose (82.5 ± 2.8 (mean ± SEM) per cent and 80.7 ± 3.1 per cent respectively for one-position and two-position studies) was deposited on a single localized area in the anterior one-third of the nose, the initial distribution pattern being identical for each study. No significant radioaerosol was detected in the lungs. Only 18.0 ± 4.7 per cent and 15.4 ± 4.1 per cent of the dose had been removed by mucociliary action after 30 minutes, and it is probable that the remainder had not penetrated initially beyond the vestibule. Since the deposition pattern was highly localized and more than half the dose probably failed to reach the turbinates it is possible that the overall effect of nasal MDIs is suboptimal for the treatment of generalized nasal disorders.


Mass elevation and lee effects markedly influence snow lines and tree lines in high mountain systems. However, their impact on other phenomena or groups of organisms has not yet been quantified. Here we quantitatively studied their influence in the Himalaya–Tibet orogen on the distribution of ground beetles as model organisms, specifically whether the ground beetle distribution increases from the outer to the inner parts of the orogen, against latitudinal effects. We also tested whether July temperature and solar radiation are predictors of the beetle's elevational distribution ranges. Finally, we discussed the general importance of these effects for the distributional and evolutionary history of the biota of High Asia. We modelled spatially explicit estimates of variables characterizing temperature and solar radiation and correlated the variables with the respective lower elevational range of 118 species of ground beetles from 76 high-alpine locations. Both July temperature and solar radiation significantly positively correlated with the elevational ranges of high-alpine beetles. Against the latitudinal trend, the median elevation of the respective species distributions increased by 800 m from the Himalayan south face north to the Transhimalaya. Our results indicate that an increase in seasonal temperature due to mass elevation and lee effects substantially impact the regional distribution patterns of alpine ground beetles of the Himalaya–Tibet orogen and are likely to affect also other soil biota there and in mountain ranges worldwide. Since these effects must have changed during orogenesis, their potential impact must be considered when biogeographic scenarios based on geological models are derived. As this has not been the practice, we believe that large biases likely exist in many paleoecological and evolutionary studies dealing with the biota from the Himalaya-Tibet orogen and mountain ranges worldwide.


Japan's experience shows that very negative circumstances are required for a country to suffer from protracted deflation. The comparison of Japan's developments in the last few years with those of the US points to large differences, which suggest that the risk of deflation in the US is low. However, the analysis of the deflation spiral in Japan could be useful to draw lessons for other countries. The first lesson to draw is that deflation is very costly and that it is difficult to anticipate. Authorities should, thus, react aggressively to avoid zero interest rates, since reaching the zero bound drastically reduces the effectiveness of monetary policy. Before reaching the zero-bound, it seems useful to adopt an inflation targeting regime, perhaps accompanied by an explicit compromise of maintaining interest rates at very low levels for a predetermined period. When zero bound is reached, the authorities still have policy instruments to fight against deflation, among them heterodox monetary measures, expansionary fiscal policy and/or substantial exchange rate depreciation. The case of Japan points to the large potential costs of these options, in terms of the central bank's balance sheet, the sustainability of the fiscal accounts and, potentially, the stability of the international monetary system. However, Japan's protracted stagnation and deflation is bound to be more costly.


Governance and public policies of coastal water quality in the « Pertuis Charentais » The coastal area of the Charente-Maritime region is highly attractive and mainly used for economic and recreational activities. Each year, 3 million tourists visit this territory stretching over 460 kilometers of coastline. According to the National Statistics Institute, more than 6.5% of the local economy relies on tourism. The Pertuis Charentais, which are the receptacle of three rivers (the Sevre-Niortaise, the Charente and the Seudre), create a good natural environment for shellfish farming. The shellfish sector is an additional structuring activity. It shapes land and sea territories and contributes to the development of the department identity. In terms of economics, shellfish farming achieves a turnover of 350 million euros and generates nearly 25,000 direct jobs. 23% (50,000 tones) out of the 217,000 tones of shellfish sold in 2016 were shipped by companies located in this department. Given the importance of its coastal activities, the water quality is of major importance and represents a challenge for the Charente-Maritime. Poor water quality is detrimental to the life of the biodiversity living there. Poor conditions will thus affect the water, its usage and the various environments. People's health and safety may also be impacted. If a potential toxic bacteria or microscopic algae was likely to develop, bathing could become dangerous and be prohibited. Poor chemical status could lead to the closure of shore fishing areas, having consequences on both professional and recreational fishing. Bacteriological contamination could affect aquaculture meaning the coastal shellfish could not be sold. These degradations are Chapter written


Mechanisms supplying nitrogen (N) to phytoplankton, and thus constraining the levels of export production, over the oligotrophic subtropical Atlantic are assessed along a meridional transect. Stable nitrogen isotope signals reveal a localized region of N2 fixation over the northern subtropical gyre. Elsewhere, particulate organic nitrogen was isotopically enriched and there was no widespread evidence of a trophic bias. Thus phytoplankton are utilizing an enriched source of N along the transect through much of the oligotrophic Atlantic, which may reflect utilization of nitrate from the deep ocean or, possibly, a supply of dissolved organic nitrogen (DON) from a non‐N2 fixing source. While there is a significant supply of DON over the subtropical gyres, reaching 0.15 mol Nm−2 yr−1, less than 10% of the DON is semilabile and thus only implies a relatively small contribution to the nitrogen supply required for export production. Over the central part of the subtropical gyres, the supply of N to phytoplankton is probably from nitrate in the underlying thermocline, possibly from convection and diapycnic transfer, or more likely, from finescale upwelling by mesoscale eddies and frontal circulations. The lateral supply of dissolved organic phosphorus (DOP) appears to be a factor of 2–3 times more important than the lateral supply of semilabile DON, and thus might play a role in contributing to the phosphorus (P) supply for phytoplankton. The lateral supply of DON and DOP might also be important in closing the N and P budgets over the North Atlantic.


Abstract. In this study we evaluate simulated surface SO2 and sulphate (SO42−) concentrations from the United Kingdom Earth System Model (UKESM1) against observations from ground based measurement networks in the USA and Europe for the period 1987 to 2014. We find that UKESM1 captures the historical trend for decreasing concentrations of atmospheric SO2 and SO42− in both Europe and the USA over the period 1987 to 2014. However, in the polluted regions of the eastern USA and Europe, UKESM1 over-predicts surface SO2 concentrations by a factor of 3, while under-predicting surface SO42− concentrations by 25–35 %. In the cleaner western USA, the model over-predicts both surface SO2 and SO42− concentrations by a factor of 12 and 1.5 respectively. We find that UKESM1's bias in surface SO2 and SO42− concentrations is variable according to region and season. We also evaluate UKESM1 against total column SO2 from the Ozone Monitoring Instrument (OMI) using an updated data product. This comparison provides information about the model's global performance, finding that UKESM1 over predicts total column SO2 over much of the globe, including the large source regions of India, China, the USA and Europe as well as over outflow regions. Finally, we assess the impact of a more realistic treatment of the model's SO2 dry deposition parameterization. This change increases SO2 dry deposition to the land and ocean surfaces, thus reducing the atmospheric loading of SO2 and SO42− . In comparison with the ground-based and satellite observations, we find that the modified parameterization reduces the model's over prediction of surface SO2 concentrations and total column SO2. Relative to the ground-based observations the simulated surface SO42− concentrations are also reduced, while the simulated SO2 dry deposition fluxes increase.


With a critical brush, this study depicts the history, the legal basis, the financial aspects and more generally the complicated process of decentralization in the Democratic Republic of the Congo (DRC), from the colonial days (1908-1960) to the provincial elections held in December 2018. A recurrent fixture of institutional design throughout the country's turbulent history, decentralization constitutes one of the most ambitious projects of the 2006 Congolese Constitution and certainly one of the most challenging areas of administrative law in the DRC. Short of a federal state, the DRC is in terms of Constitution a highly decentralized state. The Constitution divides the former 11 provinces into 26 new territorial units. However, the process has hit a slew of difficult hurdles. Overall, it emerges that the rolling out of the decentralization policy and its timing have been significantly driven by political calculations more than resource constraints, recently by an attempt by the ruling government to divide provinces into smaller ones in order to prolong its rule. Even after the effective partition of the 11 former provinces, the process still suffers further complications, for example, delays and logistic problems in electing new governors in 2015, which in turn led to litigation before the Constitutional Court in September that year. These difficulties take place in a broader context of even greater challenges. The latter include insufficient capacity of provincial administrators, fiscal decentralization, the questionable economic viability of most provinces, and repeated internal wrangling that has already culminated in the removal or resignation of governors in several provinces. The trials and tribulations of decentralization in Africa's second largest country – and one of its most populous, least developed yet resource-richest countries – will enlighten experts and policy makers in other countries. This case study straddles the fields of law, politics and history. It can thus considerably serve constitutional lawyers, policy makers and historians in other countries.


Convolutional neural networks (CNNs) provide a dramatically powerful class of models, but are subject to traditional convolution that can merely aggregate permutation-ordered and dimension-equal local inputs. It causes that CNNs are allowed to only manage signals on Euclidean or grid-like domains (e.g., images), not ones on non-Euclidean or graph domains (e.g., traffic networks). To eliminate this limitation, we develop a local-aggregation function, a sharable nonlinear operation, to aggregate permutation-unordered and dimension-unequal local inputs on non-Euclidean domains. In the context of the function approximation theory, the local-aggregation function is parameterized with a group of orthonormal polynomials in an effective and efficient manner. By replacing the traditional convolution in CNNs with the parameterized local-aggregation function, Local-Aggregation Graph Networks (LAGNs) are readily established, which enable to fit nonlinear functions without activation functions and can be expediently trained with the standard back-propagation. Extensive experiments on various datasets strongly demonstrate the effectiveness and efficiency of LAGNs, leading to superior performance on numerous pattern recognition and machine learning tasks, including text categorization, molecular activity detection, taxi flow prediction, and image classification.


As with the rest of the world, Belarus has been affected by the global economic crisis. However, the main consequences for the country were less economic, but rather political in nature. Although closely connected with Russia, it was not the spill-over of the crisis, such as the reduction in its hitherto 'miraculous' levels of economic growth to almost nothing in one year, that hit Belarus hard. Instead, it was Russia's deliberate politics of 'pragmatization', directed at its 'near abroad' to facilitate compliance of and interdependence with its neighbours, which dramatically altered Belarus's foreign policy landscape. The two principal corollaries of the global crisis for Belarus therefore included the new and irreversible search (successful or otherwise) for diversification away from Russia, and the reinvigorated sense of sovereignty with which Belarus now attempts to rebuild itself domestically and internationally.


Physical activity is known to promote the health and well-being of the population. When people are unable to perform a classical physical activity due to disability, age or disease, we will talk about Adapted Physical Activity (APA). For these people, the practice of such activity has an important role to prevent the loss of independence and to fight against post hospitalization deconditioning. In the current climate, recommendations for physical activity have been published. However, to ensure the effectiveness and safety of patients, it is important to customize the APA by analyzing and quantifying it. Various tools exist to measure it. The main objective will be to find the measurement method which best suit the patient according to his personal physical abilities and to adapt the APA program for his return home.


The design, properties and even definitions of cocrystals continue to receive considerable attention. Our understanding of the way in which molecules communicate and assemble is still incomplete, which means that supramolecular synthesis of discrete or extended molecular assemblies held together by noncovalent forces, remains a major fundamental scientific challenge. In this presentation, we outline a hypothesisdriven three-step protocol for the construction of ternary cocrystals and supermolecules where stoichiometry and primary intermolecular interactions can be readily rationalized [1-5].


Rituximab (MabThera/Rituxan) is a therapeutic monoclonal antibody against CD20, an antigen expressed by B cells but not B-cell progenitor or plasma cells. It is currently approved for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) and is well tolerated and efficacious. A small open-label study (conducted by Edwards and Cambridge) indicated that selective depletion of B cells using rituximab led to sustained benefits for patients with active rheumatoid arthritis. A 24-week, double-blind, randomized controlled trial was carried out to confirm these initial observations. In total, 161 patients with active rheumatoid arthritis were randomized to one of four treatment groups: rituximab monotherapy; rituximab plus methotrexate (R+MTX); rituximab plus cyclophosphamide (R+CTX); or methotrexate alone (MTX). Rituximab was administered as two 1000 mg infusions on days 1 and 15. An analysis at 24 weeks showed that the proportion of patients achieving an ACR20 response was significantly greater (P < or = 0.025 for all three comparisons) in all the rituximab groups compared with the MTX control group (rituximab alone, 65%; R+CTX, 76%; R+MTX, 73%; MTX alone, 38%). Both ACR50 (43 vs 13%; P = 0.005) and ACR70 (23 vs 5%; P = 0.048) responses were also significantly higher for the R+MTX group compared with the MTX group. The rituximab groups showed no significant safety differences compared with the MTX arm. The majority of adverse events were of mild to moderate intensity. Rituximab is a novel targeted therapy for the treatment of rheumatoid arthritis and it appears to be highly effective, safe and well tolerated.


A great number of element correlations have been observed in lunar samples. It is known from theoretical and experimental studies that in the solar nebula the elements condensed in groups according to their condensation temperatures and chemical affinities. One of these groups - the refractory elements - is represented by the early condensates or high temperature condensates (h.t.c.). From element correlations and group relations we estimate the bulk Moon to contain about 50 % of h.t.c.; the other 50%, the non-refractory portion, consists mainly of (Mg, Fe)-silicates and minor phases of about chondritic composition. Recently we have found strong evidence that most of the lunar highland samples represent mechanical mixtures of a differentiated (feldspathic) lunar component and a primary component from the last accretion stage of the Moon. The contribution of the h.t.c. in this primary material is estimated to 21 %. Hence, an inhomogeneous accretion of the Moon is indicated. After the formation of a highly refractory core relatively more and more non-refractory material was added until the Moon reached its final mass. The composition of the primary matter observed in the lunar highlands gives us an important clue to the composition of the non-refractory portion of the Moon and thus leads to a more reliable estimation of the lunar bulk composition.


ABSTRACT Although efforts to restore floodplain forests are becoming more popular in the northeastern United States, best management practices are not well defined. In this study, we demonstrate the success of a planting effort in western Massachusetts to increase the extent of a floodplain forest along the Housatonic River. Over 1700 floodplain-adapted tree saplings were planted in an old field and in two hayfields at Bartholomew's Cobble, a property located in Sheffield, Massachusetts, and individually tagged to follow their growth and survival. Planted trees had relatively high rates of survival over a 6 y period, especially the two most commonly planted tree species: silver maple (Acer saccharinum, 42.5% survival) and boxelder (Acer negundo, 71.7%), although plantings were more successful in the old field compared to the two hayfields. Tree dbh after 6 y differed across fields for silver maples and boxelders with those planted within the old meadow significantly larger than those planted into hayfields (silver maple dbh 9.8 cm old field vs. 6.5–6.6 cm hayfields; boxelder dbh 10.4 cm old field vs. 4.4–6.6 cm hayfields). By documenting which floodplain-adapted tree species were successful in establishing under which conditions, our observational study provides valuable insights for future restoration efforts.


This study aims to determine the form of criminal responsibility to the crime of legislative elections in Semarang; and obstacles in the implementation of criminal law enforcement against criminal acts of the legislative elections in the city of Semarang.The results showed that the process of law enforcement against criminal acts in general legislative elections held in the context of the criminal justice system in Indonesia, which includes the process of investigation by the police, prosecution by prosecutors and sentencing / verdict by the District Court. Criminal investigations are conducted legislative elections Police, in accordance with the provisions of Article 1 Paragraph (13) of Act No. 2 of 2002 on the Indonesian National Police. In the organization of the legislative elections, in the enforcement of the criminal acts of the legislative elections undergone many obstacles such as: Non-fulfillment of formal requirements and substantive a report criminal election, which resulted election supervisors or investigators difficulty to follow up a report, on terms materially one of them seek witnesses were very hard done by the Election Supervisory; The absence of witnesses because people who know the incident did not dare to testify due to intimidation;The limited time handling criminal offense elections, at both or election supervisory level law enforcement officers.Keywords: Criminal Liability; Crime; Legislative Election.


A novel experimental technique was used to investigate the in-cylinder air-fuel ratio excursions of a port-injected spark-ignition engine during load and fuel transients. This involved sampling directly from the engine cylinder using a fast flame ionisation detector (FID) system throughout an engine transient test. All tests were conducted with the coolant at the normal operating temperature of 90°C. The research engine used was a 1.6ltr four-cylinder multi-point fuel injection spark-ignition (SI) engine with four-valves-per-cylinder, with sequential injection and an electronic management system. The engine transient involved a rapid throttle opening within about 15msec. Various load steps were investigated at 2000rev/min along with the effect of altering the type of fuel injector. It was found that the response of the engine to a load transient involved a lean air-fuel ratio excursion (maximum gravimetric air-fuel ratio of about 25:1) lasting for only a single cycle, followed by a rich air-fuel ratio excursion (minimum air-fuel ratio of about 10:1) which decayed towards stoichiometric air-fuel ratio after about 10 cycles. © Copyright 1996 Society of Automotive Engineers, Inc.


This report details the histopathologic findings in a unique fibrosing disorder that recently emerged among patients with renal disease. The affected patients were initially identified among recipients of renal transplants at a single institution, but later cases at other centers were identified, and included patients receiving renal dialysis for a variety of different kidney diseases. The cutaneous changes consisted largely of indurated plaques and papules on the extremities and trunk. Systemic findings seen in scleromyxedema, which the condition resembles in some respects, were absent. By routine microscopy, the findings range from a very subtle proliferation of dermal fibroblasts in early lesions, to a florid proliferation of fibroblasts and dendritic cells in fully developed cases. Thick collagen bundles with surrounding clefts are a prominent finding, and a variable increase in dermal mucin and elastic fibers was usually evident with special stains. CD-34 positive dermal dendrocytes were floridly abundant, with dendritic processes aligned with elastic fibers and around collagen bundles in a dense network. Factor XIIIa and CD-68 positive mono-and multinucleated cells are also present in increased numbers. Electron microscopy highlighted increased elastic fibers closely apposed to dendritic cell processes. The entire dermis was commonly involved, with increased spindle cells, collagen, mucin, and elastic fibers extending through the subcutis along the septa of fatty lobules. In some instances, the process resembled a sarcoma on histopathologic examination. The recent emergence of this condition and the apparent clustering of cases in specific dialysis centers initially suggested a possible infectious and/or toxic agent. To date, however, no such agent has been identified. We propose the term "nephrogenic fibrosing dermopathy (NFD)" until a specific cause can be identified.


The use of hollow section columns in steel construction is presently hindered by the lack of adequate connection technologies. Due to access constraints, standard bolting techniques are difficult to achieve, if not impossible without welding. As an alternative to welding, blind-bolting techniques were developed to provide desirable bolted configurations, allowing hollow column frames to be erected in the same way as open profile column frames. But the current blind-bolting techniques are restricted to the construction of simple connections because of their difficulties in achieving sufficient tensile stiffness.

More recently, a novel anchored blind-bolt, labelled the Extended Hollo-bolt (EHB), has been developed at the University of Nottingham; as a modification of the standard Hollo-bolt. For the proposed connection technology, its potential in providing moment-resistance has been assessed successfully. However, the existing data related to the performance of this novel connector in tension is insufficient to permit its design. This work investigates the performance of the EHB blind-bolt under tension loading and focuses on determining, and modelling the stiffness of this novel technology in such a way to enable its application within the component method approach.

An extensive experimental programme was devised to collect sufficient component characteristic data to enable the development of an EHB component model. This covered data deals with the overall response of the connector and the individual responses of its contributing elements. A total of 51 experimental pull-out tests and 20 pre-load tests have been performed.

The force-displacement behaviour of the investigated joint component was determined under monotonic pull-out testing, where remote video gauge techniques have been adopted to capture the full non-linear response of the component, alongside traditional techniques to confirm the reliability of the data. The test matrix varies the grade and size of the component's internal bolt, the strength of concrete, and the depth of its mechanical anchorage. From the pull-out tests it was identified that the EHB component can ultimately develop the full tensile capacity of its internal bolt. This ultimate failure mode is confirmed for the range of parameters that was covered in this study. Increasing concrete strength had the most enhancing effect on the response of the component.

A secondary programme was related to the measurement of pre-load that is induced in the internal bolt of the EHB component at its tightening stage; where pre-load was monitored over a five day period. The test matrix varies the grade and size of its internal bolt, and also considers various bolt batches. It was concluded that the relative level of component pre-load to ultimate strength increased only in the case where higher bolt grades were used.

To model the tension behaviour of the EHB component, a mechanical model was developed that is based on an assembly of the component's different sources of deformation. The component model employs idealised springs with tetra-linear characteristics for the elongation of Its Internal bolt element, and springs with tri-linear characteristics for the slip of its expanding sleeves and mechanical anchorage elements. By comparing the predictions of the component model with relevant experimental data, the component model has been shown to be capable of describing the EHB component response with reasonable accuracy; capturing its tensile stiffness and its yielding trend. The accuracy of the component model has also been assessed in exclusion of pre-load effects. It was found that if the level of pre-load Is excluded from the assembly process, this can have highly undesirable effects on the predictions of the component's response. The findings of the supplementary pre-load testing programme assisted greatly in the accuracy of the component model by providing the necessary levels of pre-load.

The proposed component model has demonstrated that the behaviour of the EHB component can be modelled by the component method approach; by employing Idealised models for the behaviour of its contributing elements. The validated component model is considered to simulate the tension behaviour of the novel anchored blind-bolt with sufficient fidelity that it can be considered as a benchmark for further studies.


Cancer is a major cause of death worldwide with an increasing incidence rate and is considered a major public health problem. Distance metastasis to other tissues, high toxicity, and drug resistance of cancer cells to chemotherapy demand novel therapeutic approaches to treat cancer. Natural compounds from medicinal plants have been studied for therapeutic use in various malignancies. Nimbolide is an active principal compound from Azadirachta indica, which is an Asian traditional medicinal plant utilized historically as a remedy for a variety of diseases due to its antioxidant, anti-inflammatory, anti-cancer, and antimicrobial properties. It is a limonoid triterpene possessing potent anti-cancer effects in various types of cancers. It has been reported to induce multiple cytotoxic effects in tumor cells by modulating the cell proliferation, cell cycle, apoptosis, and metastasis by altering the various molecular signaling pathways. In the present review, we summarized all the in vitro and in vivo studies reporting the molecular targets of nimbolide for the therapeutic approaches in different types of cancer cells. We analyzed research publications up to September 2021 on the effect of nimbolide in various malignancies and the molecular mechanism of action. Nimbolide targets different signaling pathways including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), insulin like growth factor (IGF), Wingless and INT-1 (Wnt)/β-catenin, mitogen-activated protein kinases (MAPK)/c-Jun N-terminal kinases (JNK), phosphoinositide 3-kinase (PI3K)/AKT, tumor necrosis factor-α (TNF-α)/nuclear factor kappa B (NF-κβ), and death receptor 5 (DR5) in several cancer cells. Nimbolide's widespread availability and absence of side effects, as well as understanding the molecular mechanism of nimbolide's action, will be useful to develop a therapeutic agent against cancer.


A numerical approach is presented for computing the macroscopic permeability of fibrous porous media taking into account for various fiber types in hexagonal arrangement. A model based on Lattice Boltzmann Method(LBM) for viscous, incompressible flow through a regular array of fibers is employed for predicting the permeability of this media. The effect of porosity on the macroscopic permeability is studied. Such microstructure parameter as fiber shape is varied. The results show that the fiber shape significantly affects the permeability of this media in different porosity.


Nowadays people are more health conscious; they monitor the ingredients and nutrients of what they eat. Fruits and vegetables, which are rich of phytochemicals, are always chosen as a good diet. Phytochemicals are rich of nutrients and can give health benefits to the takers. Previous research has modelled the phytochemicals into its chemical structure and colours according to group of fruits and vegetables ontologically. However, there is no semantic web representation of that ontology model that makes the information more sharable among users. Therefore, in this paper, we develop a semantic web for phytochemical ontology model by linking the user interface to ontology model using JENA framework. The data from the ontology is read by using SPARQL query to display information to the front-end user. By having this semantic web representation, it is hoped that the knowledge is more accessible and shareable among intended users.


The CPX method (ISO/DIS 11819-2) was developed to measure the influence of tyre/road noise on different road surfaces, using one or two reference tyres mounted on a trailer/vehicle. In recent years, the CPX trailer has been used to compare the noise behaviour of different passenger car tyres using the tyre load (3200 N) and inflation pressure (200 kPa) specified in the standard. Several experts on tyre/road noise question whether this method is appropriate for such use, and specifically whether measured values can be compared with the labelling values. The labelling values are based on coast-by conditions as defined in ECE Reg.117, with a loading and tyre pressure that differs from the CPX method. To investigate the influence of the test conditions on the measured noise levels, two tests were conducted: 1) A test according to the specifications of ISO 11819-2 and 2) A test according to the specifications of ECE Reg.117, but with a CPX trailer instead of a vehicle. A total of 11 passenger car tyres have been tested, including two tyres designed for electric vehicles. Measurements have been done on 7 different SMA road surfaces. The paper presents both A-weighted overall noise levels and third octave band spectra. The main conclusion is that the change in loading and tyre pressure did not improve the correlation with the label values.


Abstract We evaluated the effect of chemical fertilizer and manure applications on N2O emission from a managed grassland by establishing three treatment plots of chemical N fertilizer (chemical fertilizer), manure combined with chemical N fertilizer (manure) and no N fertilizer (control) at the Shizunai Experimental Livestock Farm in southern Hokkaido, Japan. The N2O fluxes from the soils were measured using a closed-chamber method from May 2005 to April 2008. Soil denitrifying enzyme activity (DEA) in the root-mat layer (0–2.5 cm) and in the mineral soil layer (2.5–5 cm) of each treatment plot was measured using an acetylene inhibition method after treatment with NO3 −-N addition, glucose addition, both NO3 −-N and glucose addition or neither NO3 −-N nor glucose addition. Annual N2O emission ranged from 0.6 to 4.9 kg N2O-N ha−1year−1, with the highest emission observed in the manure plot and the lowest in the control plot. The chemical fertilizer induced emission factor (EF) (range: 0.85–1.32%) was significantly higher than the manure-induced EF (range: 0.35–0.85%). The denitrification potential of the soil horizons was measured with the addition of both NO3 −-N and glucose, and was significantly higher in root-mat soil than in mineral soil. Soil DEA in the root mat with the addition of NO3 −-N with and without the addition of glucose had a significantly positive correlation with soil pH (P < 0.05). Soil pH was significantly influenced by N source, which was significantly lower in the chemical fertilizer plot than in the control and manure plots. For a fixed quantity of available N, the application of manure could result in higher N2O emission compared with chemical fertilizer, owing to higher soil pH values under manure application than under chemical fertilizer application.


Adult male rats were fed on either low-K or normo-K diet for 3 months. Gossypol acetic acid was given po to all rats in a daily dose of 15 mg/kg, 6 d/wk for the same period of time. At the end of the regimen, plasma K+ concentration was determined and testicular histology examined. The plasma K+ concentration of the rats fed on low-K diet was far lower than both the reported normal value and the value of the rats fed on normo-K diet, indicating a K deficient status of the former. Both the extent and severity of damage of seminiferous epithelia were significantly more pronounced in low-K fed than in normo-K fed rets. It is concluded that the antisperma-togenic activity of gossypol can be enhanced by K deficiency. a contributing factor in the development of gossypol-induced sterility.


Abstract Objective: To assess long-term cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) combined subtype. Methods: 223 otherwise healthy adults (≥18 years of age) with ADHD combined subtype were exposed to ≤24 months of MAS XR (20–60 mg/day). Resting sitting diastolic blood pressure (DBP) and systolic blood pressur (SBP) and pulse were measured at baseline and weekly, then monthly during long-term treatment. Twelve-lead electrocardiograms were obtained at screening/baseline, weekly, then at 3-and 6-month intervals up to 24 months. Findings: With MAS XR 20–60 mg/day, mean changes in DBP (1.3±9.2 mm Hg; P=.O42), SBP (2.3±12.5 mmHg; P=.OO6), and pulse (2.1±13.4 bpm; P=.019) were small and not clinically significant. A clinically insignificant increase in QTcB (corrected by Bazett's formula) interval (7.2 msec; P<.001) was observed at 24 months. No subject exhibited QTcB interval >480 msec (QTcF [corrected by Fridericia's formula] >454 msec). Seven subjects discontinued due to a car-diovascular adverse event (hypertension, n=5, palpitation/tachycardia, n=2); none of these events was reported as serious. Few subjects with normal baseline vital signs (using approved parameters at the time of study initiation) exhibited clinically significant abnormalities at end point; several subjects with borderline baseline values exhibited shifts to abnormal values during MAS XR therapy. Conclusion: Cardiovascular effects of long-term MAS XR (≤60 mg/day) were minimal in otherwise healthy adults with ADHD. Nevertheless, vital signs should be monitored prior to and during treatment with any stimulant.


Commercially available Thermit (Al + Fe/sub 3/O/sub 4/) was ignited, forming a molten mixture of Al/sub 2/O/sub 3/ + Fe. The subsequent mixing of this melt with water in steel containers produced explosive interactions that were used to model hydrovolcanic activity. Debris collected from the experiments consisted of quenched Thermit particles ranging in size from < 1 ..mu..m to centimeters. Scanning electron microscopy of the debris showed spheroidal, irregular aggregates and blocky particle shapes that are very similar to hydrovolcanic ash, as well as some types of stratospheric dust and industrial fly ash. 27 references, 3 figures, 1 table.


Summary The considerable falls in viscosity of sodium caseinate solutions under the action of rennet are shown to be due to changes in volume and shape (or either alone) of loosely coiled long chain molecules, resulting from the discharge of ionization ('Third-type electro-viscous effects'). This reduction may be as well effected by small amounts of NaCl or by the separated decomposition products of the rennin-caseinate reaction. Even at the highest practicable caseinate concentrations (9–10% by weight) the solutions are truly fluid over the range of shear-rate of the Ostwald viscometers used The initial rate of fall of viscosity is found to be proportional to the maximum (initial) specific viscosity, leading to an equation Xk1 = 1/τ where X the proportional viscosity loss, varies with the source of caseinate but is constant for all normal rennets; k1, the first-order reaction constant, varies with the rennet but is independent of the source of casein over a wide range; and τ, which has the dimensions of time, varies with both caseinate and rennet. The parameter k1 may be found either from the exponential viscosity fall or calculated from the asymptotic initial slope and has been shown to serve as a useful index of rennet activity. This method of rennet testing does not depend on the keeping qualities of rennins, rennets, milks or caseinates. Details of the preparation of caseinates and of the methods for practical testing of commercial rennets are given.


The formation of fields of standing surface acoustic waves (SAW) in LiNbO/sub 3/ and La/sub 3/Ga/sub 5/SiO/sub 14/ (LGS) crystals was studied by high-resolution topography method on a laboratory X-ray source. The fields of standing SAW were formed using SAW-resonator structures consisting of interdigital transducer (IDT) and reflecting gratings. The SAW amplitudes and power flow angles were measured by X-ray topography, diffraction in acoustic beam was visualized, and the SAW interaction with the crystal structure defects was studied.


The main problem in underwater passive acoustic (UPA) detection was to separate unknown independent signals that propagate from unknown directions. Few algorithms can separate multiple signals and find their directions when there is no a priori knowledge about signals and their directions. We propose an improved algorithm to resolve this problem, allowing the element weights to be adapted to the element delays, which could possibly increase performance and speed up convergence. It is using the narrowband assumption and adjusting complex weights other than delays. Real radiated noises of ships and computer simulation data are used to test the improved algorithm. The results of the experiments reveal the signal separation performance and convergence rate are superior to independent component analysis blind Beamformer. The sampling rate could also be less because phase shifts are used instead of time shifts.


This paper reports on one stage of a European Union (EU)-funded project, Intercultural Education of Nurses and health professionals in Europe 2 (IENE2), that aimed to contribute to the vocational education and training (VET) of nurses andother healthcare professionals in Europe by enhancing the capacity of teachers to promote intercultural dialogue and the development of students' ability to provide culturally competent care. A previous project (IENE1) produced a model for the development of cultural competence for use in the participating institutions. The project reported in this paper describes the transfer of this innovation to a wider audience. A needs analysis of a sample of teachers identified their training needs in relation to integrating the model into their curricula to prepare their students to work in multicultural environments and/or other European countries. The opinions of health services employers and senior managers were also elicited. The results of this investigation informed the production of a Train the Trainer package for use in a series of workshops for teachers in participating organisations.


Retroviruses are relevant human pathogens affecting the lives of tens of millions of people globally each year and resulting in nearly 2 million deaths annually. Understanding the process of retrovirus infection has wide benefits including the identification of therapeutic targets to treat HIV/AIDS and better understanding of cellular pathways disrupted in diseases, such as cancer and AIDS. Here, I first present my role in a collaborative project that led to the identification of over 200 cellular factors with potentially important roles in the early stages of retrovirus infection. We identified these factors through a genome-wide siRNA screen and through characterization of interactions between host and virus proteins. Additionally, I present my work on ZASC1, a host cell transcription factor that binds to the promoter regions of both HIV-1 and MLV and regulates virus gene expression in cultured established cell lines. I generated a ZASC1 knockout mouse model, showing that this gene is non-essential to development and reproduction. This mouse model was used to characterize the role of ZASC1 in retrovirus replication and disease pathogenesis. I showed that ZASC1 influences myeloid cell differentiation in this compartment and that this transcription factor is required for efficient early Mo-MuLV infection in the bone marrow compartment. Through studies of Mo-MuLV pathogenesis in the ZASC1 knockout mouse model, I show that despite this early defect, tumorigenesis is not regulated by ZASC1


CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and TNF-α secretion by DCs.


A major research program underway at Loughborough University involves the generation of ultrahigh magnetic fields up to 300 T (3 MG) by means of magnetic flux-compression. A high pulsed current is discharged into a single-turn driving coil surrounding a liner, with various aspects of the associated practical work being presented in a companion paper. This paper explains the two-dimensional filamentary modeling technique that is used to provide detailed prediction of the liner implosion, driving coil dynamics and magnetic field diffusion through all the metallic elements of the arrangement. The main typical results from numerical experiments are presented and experimental data are compared with theoretical predictions.


Theranostics: towards postgenomic diagnostics Theranostics is a portmanteau word created by linguistically blending 'therapeutics' and 'diagnostics'. Theranostics has indeed turned over a new leaf for medical diagnostics in the postgenomics era. The new concept of theranostics is made possible by integrating the application of molecular biomarkers across the continuum of tests and interventions ranging from disease susceptibility testing and the monitoring of clinical outcomes resulting from interventions, such as drugs (e.g., pharmacogenomic tests), nutrition (e.g., nutrigenomic tests) and vaccines (e.g., vaccinomic tests) [1–4]. Being crucial to both human health and diseases, theranostics therefore has inherent orientation towards improving global health and widespread societal issues such as poverty and conflicts that are intimately linked with health [3,4]. Theranostics involves a variety of biotechnological inventions including the data-intensive platforms (genomics, proteomics and metabolomics) nanotechnology and hybrid assay platforms as exemplified by nano proteomics. Seen in this light, the concept of theranostics is markedly broader than the classic notion of personalized medicine or biomarkers that draw moderately from a singular biotechnology platform such as high-throughput genotyping. Theranostics is emerging at a time when there is growing interest in ecosystem health – another strand of conceptual extension in postgenomic diagnostics currently being accelerated by theranostics. Indeed, the initial findings of the Human Microbiome Project (HMP) announced in June 2012 have suggested the need for considering theranostics under the holistic rubric of 'one health'. The HMP data thus far have shown that microbial communities and their genes (the microbiome) inextricably co-exist throughout the human body, with fundamental roles in both human and ecosystem health [5]. In fact, there is emerging evidence that human microbiomes are implicated in conditions such as malnutrition despite adequate access to food and commonly known chronic diseases (e.g., Type 2 diabetes and obesity) [5,6]. Although many of these human diseases appear to run strongly in families, research in genetics has not been able to elucidate the causative genes in a commensurate manner – that is, the so-called 'missing heritability'. It could be that some of the heritable components of common human diseases may rest in the microbiomes that can be passed on through generations. Hence, viewing human beings as 'walking ecosystems' that contain many collaborating and competing species provides clues for another possibility: the new generation of postgenomic theranostics may very well be harnessed, not only from the keen knowledge of the host (human organism), but also from the biological variations in the microbiomes. Finally, it is noteworthy that such remarkably broad range of postgenomic diagnostics anticipated to emerge from theranostics R&D is also embedded in vast societal expectations, whether by governments, industry or citizens, in the 'bioeconomy' and knowledge-based Vural Özdemir


Comparison of physico-chemical quality of strawberry fruit cv. Praratchatan 60, 72 and 80 at 25, 50 and 75% color break was investigated. Strawberry fruit cv. Praratchatan 60 and 72 had prominent numbers of conic-shaped fruit which were 77.78 and 62.22%, respectively, while moderate numbers were found in strawberry fruit cv. Praratchatan 80 (46.67%). Fruit weights and fruit sizes in terms of width, length and thickness were different among three cultivars. Strawberry fruit characteristics and chemical properties also varied among cultivars and color break stages which appeared in the surface color, flesh color, firmness, soluble solids content (SSC), titratable acidity (TA) and vitamin C content. Strawberry fruit cv.Praratchatan 60 had the highest total soluble phenolics (TSP) and antioxidant activity (AA). Besides, AA from crude extracts of three strawberry cultivars notably correlated to their TSP (correlation coefficient (R) of 0.976). Furthermore, strawberry fruit harvested at 75% color break had higher SSC, vitamin C and anthocyanin content while being lower in firmness, TA, TSP and AA compared to those harvested at 25 and 50% color break.


High percentages of Micro and Small-sized enterprises (MSEs) perish in their initials years of business. That is why various efforts have been made to know their operation and improve it. However those proposals of improvement are mostly based in reductionist diagnostics that limit the understanding of their business processes. This paper presents an integral diagnostic of MSEs, specifically in the service sector in the north of Mexico, through which the maturity level of its processes is determined. The design was descriptive exploratory with a quantitative approach. A rubric-type instrument was applied, which was designed to perform an integral diagnosis and measure the maturity level of the processes in 140 companies. The results indicate that the maturity levels of the business processes in the service sector are mostly craft-like. The elements with the lowest maturity levels include service assessment as part of management, the capacity to design new services/processes, evaluation and selection of suppliers, and improvements to the purchasing process that can assure an appropriate level of service. The need to implement improvement projects in areas related to planning, monitoring, control and information support systems were also detected. The main contribution of this work is having defined the service sector of the municipality where the organizations under study are located, which will help entrepreneurs in the sector, to improve their knowledge on the area in which they operate; researchers decide to make more contributions to the sector; and clients obtain information about the business they purchase from.


To evaluate the preventive effects of combined vaccination for Pasteurella multocida, Mannheimia haemolytica and Histophilus somni on respiratory diseases in Japanese Black calves, 295 calves at one farm were alternately assigned to two groups; 147 calves received the vaccine at 4 and 8 weeks of age (vaccination group), and the other 148 calves did not receive vaccine (control group). The incidences of respiratory diseases were 25.9 and 70.9% in the vaccination and control groups, respectively, and the odds ratio for comparison between the two groups was 0.143 (95% confidence interval: 0.086–0.238). Administration of the multiple vaccine to Japanese black calves might be one of effective factor for prevention of respiratory diseases.


The quasi Fermi level for electrons in a soft perovskite crystalline thin film and the contact qualities at the PCBM/perovskite and perovskite/P3CT-Na interfaces can be increased using a facile encapsulation method, which improves the device performance and stability of the resultant perovskite solar cells. In the encapsulated perovskite solar cells, the averaged open-circuit voltage (VOC) largely increases from 0.981 V to 1.090 V after 9 days mainly due to the increased quasi Fermi levels. Besides, the reflectance and photoluminescence (PL) spectra show improved contact qualities at the PCBM/perovskite and perovskite/P3CT-Na interfaces, which can be used to explain the increase in the short-circuit current density (JSC) from 21.68 mA cm-2 to 23.48 mA cm-2 after the encapsulation process. Besides, nanosecond time-resolved PL and temperature-dependent PL spectra can be used to explain the increased VOC, which is mainly due to the increased shallow defect density and thereby increasing the exciton binding energy of the encapsulated perovskite sample. It is noted that the averaged power conversion efficiency (PCE) slowly decreases from 18.24% to 16.52% within 45 days.


Background The volume of specialty care referrals often outstrips specialists' capacity. The Department of Veterans Affairs launched a system of referral coordination to augment our workforce, empowering registered nurses to use decision support tools to triage specialty referrals. While task shifting may improve access, there is limited evidence regarding the relative quality of nurses' triage decisions to ensure such management is safe. Objective Within the specialty of sleep medicine, we compared receipt of contraindicated testing for obstructive sleep apnoea (OSA) between patients triaged to sleep testing by nurses in the referral coordination system (RCS) relative to our traditional specialist-led system (TSS). Methods Patients referred for OSA evaluation can be triaged to either home sleep apnoea testing (HSAT) or polysomnography, and existing guidelines specify patients for whom HSAT is contraindicated. In RCS, nurses used a decision support tool to make triage decisions for sleep testing but were instructed to seek specialist oversight in complex cases. In TSS, specialists made triage decisions themselves. We performed a single-centre retrospective cohort study of patients without OSA who were referred to sleep testing between September 2018 and August 2019. Patients were assigned to triage by RCS or TSS in quasirandom fashion based on triager availability at time of referral. We compared receipt of contraindicated sleep tests between groups using a generalised linear model adjusted for day of the week and time of day of referral. Results RCS triaged 793 referrals for OSA evaluation relative to 1787 by TSS. Patients with RCS triages were at lower risk of receiving potentially contraindicated sleep tests relative risk 0.52 (95% CI 0.29 to 0.93). Conclusion Our results suggest that incorporating registered nurses into triage decision-making may improve the quality of diagnostic care for OSA.


The entry in W. H. Auden's Commonplace Book for "Justice" cautions: "Whoever suffers from the malady of being unable to endure any injustice, must never look out of the window, but stay in his room with the door shut. He would also do well, perhaps, to throw away his mirror." Susan Moller Okin suffered this malady but rejected the poet's advice. She opened the window and looked in the mirror; her writings reflect sensitivity to injustice and acute awareness that her position of privilege and her good fortune made the work she did a moral imperative. The temper of her work was set by her political sensibility to the consequences of strength and weakness and by unflagging attention to the events of our world.


Introduction: COVID-19 has spread rapidly around the world. This epidemic has created stress and anxiety for pregnant women in different parts of the world. Objective: The aim of this study was to investigate the relationship between quality of life (QoL) with anxiety, depression, coronavirus induced anxiety, sexual function (SF), and marital satisfaction (MS) in pregnant women during the Covid-19 pandemic.Methods: The present study is a cross-sectional study involving 261 pregnant women, administered through an online survey.Outcomes: The Short-Form Health Survey (SF_12), Marital Satisfaction Scale (MSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and coronavirus induced anxiety questionnaire, Padua Obsession Questionnaire, General Health Questionnaire (GHQ) are used for data collection. Data were analyzed using the Pearson correlation coefficient and path analysis.Results: The overall goodness-of-fit statistics revealed that the predictors of QoL had excellent fitness indices (RMSEA=0.02; AGFI=0.99). The results show that coronavirus induced anxiety, marital satisfaction (MS), sexual function (SF), depression, and anxiety have a direct effect on women's QoL. Among the variables, GHQ has a more direct effect on women's QoL. General health (GH) is considered as a mediator variable; variables such as anxiety, depression, and coronavirus induced anxiety with effect on GH can impress QoL. Anxiety as a main predictor of QoL, with direct and indirect effects through GH, depression, SF, and MS can impress QoL.Conclusion: Since the QoL in pregnant women is associated with coronavirus epidemics, these results can be used to plan to improve the health and QoL of these people.


Bone resorption, characterized by the solubilization of both the mineral and the organic componcnts of the osscous matrix, was obtaincd in tissue culture under thc action of parathyroid hormonc (PTH). I t was accompanied by the excretion of six lysosomal acid hydrolascs, which was in good correlation with thc progress of the resorption cvaluatcd by the release of phosphate, calcium 45 or hydroxyproline from the cxplants; there was no increased excretion of two nonlysosomal cnzymcs, alkaline phosphatase, and catalasc. Balance studics and experiments with inhibitors of protein synthesis indicated that the intracellular stores of the acid hydrolases excreted were maintained by new synthesis. The release was not due to a direct disruption of the lysosomal membrane by PTH; it is presumed to result from an exocytosis of the whole lysosomal content and to involve mechanisms similar to those controlling the secretion of this content into digestive vacuoles. The resorbing explants acidified their culture fluids at a faster rate and released more lactate and citrate than the controls; this release was in good correlation, in the PTHtreated cultures, with the resorption of the bone mineral, but the amount of citrate released was considerably smaller than that of lactate. The acid released could account for the resorption of the mineral. I t is proposed, as a working hypothesis, that the acid hydrolases of the lysosomes are active in the resorption of the organic matrix of bone and that acid, originating possibly from the stimulation of glycolysis, cares for the concomitant solubilization of bone mineral while also favoring the hydrolytic action of the lysosomal enzymes. I N T R O D U C T I O N A concomitant removal of the organic and of the mineral components of the extracellular matrix of bone is a general character of bone resorption, regardless of the type of the operant cell: osteoclast (KSlliker, 1873; Hancox, 1956), osteocyte (B6langer et al., 1963) or, possibly, other cells (Cameron et al., 1967). However, the chemical identity of the agents responsible for these phenomena and the nature of the cellular mechanisms involved in their excretion is still a matter of speculation. The participation of enzymes able to hydrolyse collagen, proteins, and mucopolysaccharides has been postulated (McLean and Urist, 1961) and 676 on A uust 8, 2017 jcb.rress.org D ow nladed fom supported by observations of collagenolytic factors in bone (Walker et al., 1964; Woods and Nichols, 1965). Similarly, the hypothesis of a secretion of chelating agents (McLean, 1954) or of acid (Weidenreich, 1930) has been put forward to explain the removal of the mineral and it received credit from studies on the metabolism of bone cells (for a review, see Vaes, 1966 b). I t is the purpose of the present paper to report and to discuss observations on biochemical and cytological processes which are presumed to be of importance in the digestion of the organic matrix: namely the synthesis and the excretion of several lysosomal hydrolases by the cells while resorbing the extraceUular framework of bone. Data which may have significance regarding the mechanisms of solubilization of the mineral (the release of acid and of large amounts of lactate by the cells) will also be reported, and, in the discussion, an hypothesis will be presented which integrates these two groups of observations. Parts of the work described have already been the object of preliminary notes (Vaes, 1965 b, 1966 a and b). M A T E R I ~ . L S A N D M E T H O D S To obtain a model system of bone resorption, advantage was taken, throughout this study, of the property of PTH 1 to stimulate this process, either in tissue culture or in vivo. Bone Resorption in Tissue Culture Calvaria (without the oecipitals) were taken off 18-19 days Swiss albino or N M R I mouse embryos, put in a drop of Hanks' solution and dissected aseptically under a Zeiss stereomicroscope; their weights varied from 1.5 to 3.5 nag, according to the stage of development. They were then introduced into 20 ml--plastic roller-tubes (1 ealvarium per tube, as a rule) and laid into 0.05 ml chicken plasma, at 2 cm from the bottom of the tube. Fixation of the explants on the wall by dotting of the plasma was favored by leaving the tubes in the horizontal position during ~,~ hr at room temperature before the addition of the culture fluid; unless otherwise specified, this consisted in 1 mi of medium 199 I Abbreviations used: C, controls; EDTA, ethylenediamine tetraacetate; N, number of determinations; N.S., nonsignificant; p, level of significance; PTE, parathyroid extract; PTH, parathyroid hormone; SD, standard deviation. containing Hanks' salt solution as a base (Morgan, et al., 1955). The tubes were laid at 37°C in an almost horizontal position on the roller-tubes drum (6 revolutions per hr) and cultivated aseptically under an atmosphere of air. The culture media were renewed after 1 or 2 days of culture (exceptionally, 3 days). Due to the low buffering capacity of medium 199, when equilibrated with air, its pH shifted from 7.4 to 8.3-8.5 during the first hours of culture at 37 ° by loss of CO2; the acidification of the culture fluids by the explants was thus manifested by a progressive lowering of the pH below 8.3-8.5. The calvaria were treated in a paired manner. Two calvaria were taken from embryos of the same litter and cut at equal sizes under the dissecting microscope; 1 USP unit/ml of PTE was added to the medium of the "resorbing" calvarium and appropriate amount (0.01 ml) of a substitute solution (0.2% phenol, 1.6% glycerol and 0.7% cristalline bovine serum albumin), to the "control." Critical experiments were repeated, using purified PTH (2500 USP units per mg) or the nonhormonal parathyroid peptides 2, 3S, and 5 (Hawker et ai. 1966) instead of the impure whole-gland extract used routinely; the solvent (0.001 N acetic acid) was then added alone to the controls. As the calvaria contain, besides bone, some fibro-cartilaginous tissue present at the sutures in between the individual bones constituting them, control experiments were a lso done in which carefully dissected parietals, containing only bone tissue, were put into culture; the two parietals from the same embryo were then paired. For the experiments requiring labeling of the embryonic bones with radioisotopic calcium 45, the pregnant mice were injected subcutaneously, 64 hr (unless otherwise specified) before being killed, with 40-90 /~c of 4SCa labeled calcium chloride (specific activity: more than 1 c/g Ca). Bone Resorption In Vivo Infant Wistar rats of either sex and up to 8 days of age (generally, between 4 and 6 days) were injected subcutaneously twice daily, at 9 a.m. and at 5 p.m., during 3 days, with either 10 USP units of PTE or an equal volume (0.1 mi) of the control solution already described; Control and PTE rats were paired within the same litter. They were killed by decapitation 15-16 hr after the last injection; the serum inorganic phosphorus concentrations were then markedly depressed in the PTE group (--33 44.6%; p < 0.001). Their whole calvaria were dissected out, immersed in ice-cold 0.25 M-sucrose and used as material for the preparation of homogenates or of cytoplasmic fractions. GILBERT VAE~ Mcvhanisms of Bone Resorption 677 on A uust 8, 2017 jcb.rress.org D ow nladed fom Preparation and Fractionation of Homogenates of Bone Tissue Pooled calvaria were minced with scissors and homogenized in 2-3 ml of 0.25 M-sucrose w i t h a motor-driven, ground-glass conical homogenizer (Potter and Elvehjem, 1936); homogenates which had not to be further fractionated were made directly in bidistilled water. The homogenates were centrifuged at 600 g during 10 roan at 0°C, yielding a cell-free supernatant ("cytoplasmic extract" or E fraction) and a sediment containing most of the nuclei together with cell debris, connective tissue elements and solid mineral (N fraction). In some experiments, the cytoplasmic extract was further fractionated by differential centrifugation, according to Vaes and Jacques (1965 a and b) to yield M, L, P, and S ("nonsedimentable") fractions. Nonsedimentable enzyme activities are expressed in per cent of the total activities assayed in the reconstituted hornogenates (sum of fractions E and N). Cultures of Isolated Fibroblasts Fibroblasts, obtained by trypsinization from the whole carcass of eviscerated 19-day rat embryos, were grown as monolayers (Paul, 1961) during 1 wk in a modified Eagle (1959) minimal essential medium supplemented with 10% calf serum; the main modifications included the substitution of 0.5% lactalbumin hydrolysate to the amino acid present in Eagle's recipe as well as increasing the glucose concentration from 0.1 to 0.45%. Subcultures (Paul, 1961), containing about 4 X l0 b cells in 3 ml medium, were cultivated in Leighton tubes with appropriate refeedings, during either 1-3 days or 7 days, to obtain, respectively, actively growing or almost stationary cultures. They were then further cultivated during 1 or 2 days in fresh medium (either Eagle-serum or medium 199) containing variable amounts of PTE or of its substitute solution. This last medium was used for the enzymatic and chemical analyses. EnzYme Assays and Analytical Procedures Most of the techniques used for the enzyme assays have been described in detail elsewhere (Vaes and Jacques, 1965a). The definition of the "free activities" of the acid hydrolases and the methods used for their measurement have also been repor,ted (Vaes, 1965a). Uni~;s of enzyme activities generally refer to the decomposition of 1 /~mole of substrate/min, except for cytochrome oxidase, catalase, and hyaluronidase, whose units have been described together with their assays '(Vaes and Jacques, 1965a). In some experiments, acid phosphatase was determined by the amount of,0-nitrophenol liberated from p-nitrophenyl phosphate. The reaction was carried out in 0.5 ml of 0.008 M-p-nitrophenylpho


Knowledge about hepatotropic viruses is crucial for pediatricians because of the high prevalence of viral hepatitis during childhood. The multiplicity of hepatotropic viruses, the spectrum of acute and chronic infections, and the sequels of viral hepatitis result in a need for physicians to better understand the clinical and epidemiological context of patients with viral hepatitis, as well as the importance of prevention measures for hepatitis. A descriptive cross-sectional study was made of pediatrician's knowledge about viral hepatitis, through questionnaires to 574 pediatricians, with no obligation of identification. The pediatricians were recruited among those who attended a national Congress of Pediatrics in Brasília, Brazil. Among these pediatricians, 50.1% frequently treated cases of hepatitis, and 74.7% indicated that they had knowledge of the existence of five hepatotropic viruses; 14.5% knew about at least four types of hepatitis complications, while only 7.7% and 4.3% were able to correctly diagnose viral hepatitis A and B, respectively. Many (28.4%) did not know how to treat the patients adequately. Only 37.5% had already recommended vaccination against hepatitis B. Only 50.2% of the pediatricians had been vaccinated against hepatitis B. We concluded that it is crucial to make pediatricians more knowledgeable about viral hepatitis, through continued education programs, especially emphasizing prevention procedures.


Background Onasemnogene abeparvovec (AVXS-101), a one-time intravenous gene-replacement therapy, treats the genetic root cause of spinal muscular atrophy (SMA). In the phase 1 study, AVXS-101 dramatically improved survival, motor function, and motor milestone achievement in SMA type 1 (SMA1) patients. Methods STR1VE is a phase 3, multicenter, open-label study (NCT03306277) in SMA1 patients <6 months (bi-allelic survival motor neuron 1 gene [SMN1] mutations/deletions, 2 SMN2 copies). Primary outcomes are independent sitting ≥30 seconds at 18 months of age, and survival (no death/permanent ventilation) at 14 months. Secondary outcomes include ability to thrive and ventilatory support at 18 months. Exploratory outcomes include CHOP-INTEND and Bayley-III. Results Enrollment is complete (22 patients dosed). Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support. Mean baseline CHOP-INTEND: 32.6 (17.0–52.0) points; increased by 6.9 (-4.0–16.0), 9.2 (0–18.0), and 11.7 (-3.0–23.0) points at 1, 2, and 3 months; independent sitting: 11/22 patients; survival at 13.6 months: 13/15 (87%) (8 March 2019 datacut). Conclusions Preliminary data from the AVXS-101 phase 3 study show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.


We conducted a survey of actual using conditions of farm-made liquid fertilizers by investigating their formulation types, materials, making processes, using methods and various beneficial effects on 29 farms certified by National Agricultural Products Quality Management Service to produce environment-friendly agricultural products in 2009. Most of the materials used to make liquid fertilizers are those that can be easily obtained around the farms. Molasses or black sugar are added as an energy source of microorganism. And leaf mold, bacterial cultures supplied by agricultural extension centers of local governments, and cultures of native microorganisms were used as microbial sources for fermenting effective microorganisms. Types of the farm-made liquid fertilizers were fermented liquid fertilizers, fermented plant juices, amino acid liquid fertilizers, calcium-liquid fertilizers, and phosphoric acid liquid fertilizers. Effects of liquid fertilizers used by the farms were found to promote plant growth by supplying nutrition, to accelerate blooming and flower bud formation, to enhance the quality of agricultural products such as increase of sugar contents and improvement of storing conditions, to induce resistance against diseases and insect pests, and to cause endurance to high temperature stress. Chemical properties of the liquid fertilizers collected were analyzed. As a result, pH and EC range showed differences according to kinds of the liquid fertilizers. Amount of macro-nutrients, such as nitrogen and phosphoric acid, in


Objective: The study documented the influence of HIV/AIDS information on the knowledge and attitudes of barbers relating to the prevention of HIV in their professional practices. Methods: Data were collected using standardized questionnaire from all the 372 commercial barbers in a Local Government Area in Ibadan. Results: Ninety three percent of the barbers had at least primary school education and 99.5% learnt barbering through apprenticeship. Those who identified sex and sharing of invasive objects with infected persons as transmission routes were 96.7% and 84.7% respectively. Preventive measures mentioned were disinfection (86.0%) and avoiding accidental cuts (87.4%). There were misconceptions like availability of cure (18%) and transmission of HIV through handshake (14.5%). Majority (64.8%) thought only visibly stained instruments were infectious and 83.3% did not know that barbers were at risk of direct infection from the clients. Those with higher education had more HIV knowledge than the less educated ones (p<0.05). Ninety-five percent agreed that equipment decontamination was the primary responsibility of barbers. Major source of information identified was mass media (95.7%). Conclusion: The occupational-specific knowledge and attitudes of the barbers about HIV/AIDS were inadequate. Mass media messages should be reinforced with pertinent information through personto-person contact.


The Tohoku tsunami, that impacted the Japanese coast in 2011, caused great damages on many offshore vertical breakwaters ranging from the erosion of the rubble mound to the partial displacement or total collapse of caissons. The breakwater failure mechanisms were function of the tsunami wave types that vary along the Japanese coast according to the bathymetry features. The Iwate coast, characterized by deep water depths and steep slopes, was mainly impacted by tsunami overflow leading in particular to the failure of the world's deepest breakwater of Kamaishi. In the shallow waters of the Sendai bay, observations showed that breakwaters protecting harbor entrances were impacted by short waves train resembling to undular bore. This work aims to investigate this latter type of tsunami wave impacts that are less reported in the literature. We chose to focus on the highly damaged offshore breakwater of Soma, located in the south part of the Sendai bay. The hydrodynamics conditions during the tsunami impact are investigated using the VARANS Thetis code (Desombre et al., 2012), which allows to simulate both the free surface flow and the flow inside the rubble mound simulated by a porous medium. The model is forced at the offshore boundaries by the Funwave Boussinesq code that describes the transformation of the tsunami waves from the source to the generation of undular bores in shallow waters. The study includes the computation of forces acting on the caissons. We discuss the relevance of describing the hydrodynamics at the short wave scale to assess breakwater stability in the course of tsunami-like undular bore impact.


Introduction IL-17 secreting CD4 T cells (Th17) are a distinct lineage of pro-inflammatory lymphocytes that develop under control of the transcription factor RORγt. Th17 cells are pathogenic in models of autoimmunity and have been implicated in the pathogenesis of several forms of liver inflammation including primary biliary cirrhosis, alcoholic and viral hepatitis. Despite their importance in perpetuating inflammation, there is little known about the molecular basis for their recruitment and positioning to specific sites such as the liver. Methods Human intrahepatic Th17 cells were isolated from explanted liver tissue without cytokine expansion and analysed by multi colour flow cytometry. Murine liver injury models of Con A hepatitis, MCD Diet and repeated CCL4 injections were used for intravital microscopic assessment of Th17 cell recruitment to the liver. Results Less that 0.25% of T cells in normal human liver expressed IL-17 but we detected IL-17 secreting cells in inflamed human liver samples with the highest frequencies detected in patients with seronegative fulminant hepatitis (median 3.7%; IQR 3.4–3.9) non-alcoholic steatohepatitis (median 3.3%; IQR 2.7–3.5%) and auto-immune hepatitis (median 2.8%; IQR 2.6–3.3%). Intrahepatic IL-17+ cells expressed RORγt and the IL-23 receptor consistent with a Th17 lineage. They secreted IL-22 and IFNγ in addition to IL-17 and expressed high levels of the chemokine receptors CCR5, CCR6, CXCR3 and CXCR6. Intravital microscopy in murine models of acute liver injury (con-A hepatitis), steatohepatitis (MCD) and chronic liver injury (CCl4) demonstrated enhanced recruitment of adoptively transferred Th17 cells to the hepatic parenchyma via the sinusoids. Recruitment was significantly reduced by a blocking the CXCR3 ligand CXCL10 which also ameliorated liver injury. The CCR6 ligand, CCL20, was restricted to biliary epithelium and secreted by cholangiocytes in vitro suggesting a further recruitment signal positions Th17 cells near bile ducts in portal tracts. Conclusion Th17 cells are recruited to sites of inflammation in the liver by sequential interactions in which the CXCR3 ligand, CXCL10 promotes recruitment into the parenchyma from blood via the sinusoids and the CCR6 ligand, CCL20 positions cells at the biliary epithelium.


In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one‐third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low‐dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg−1 per min, followed by 3 min of 0·12 µg kg−1 per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3–299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6–407·9), while increases in platelet count for approximately 31% (95% CI 187·8–314·8) and MPV for 4·4% (95% CI 7·3–10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low‐dose epinephrine infusion in conditions of decreased blood pressure.


Purpose
This study aims to examine whether accountability and culture have an impact on auditors' professional scepticism. It also examines whether culture moderates the effect of accountability on auditors' professional scepticism.

Design/methodology/approach
Three of the Big 4 firms in Australia and Egypt participated in an audit judgement experiment, which required them to indicate their beliefs about the risk of fraud and error at the planning stage of a hypothetical audit and evaluate the truthfulness of explanations provided by the client management. The authors examined whether their professional scepticism was influenced by accountability.

Findings
The results indicate professional scepticism differs significantly between cultures in some situations. The fact that culture influences scepticism suggests that even when auditors use the same standards (such as ISA 240 and ISA 600), they are likely to be applied inconsistently, even within the same firm. The authors, therefore, recommend that international bodies issue additional guidance on cultural values and consider these cultural differences when designing or adopting auditing standards.

Originality/value
To the best of the authors' knowledge, this is the first study that examines whether culture moderates the impact of accountability on auditors' professional scepticism using Egyptian and Australian (Middle Eastern and Western) auditors. Prior literature suggests that individuals subject to accountability pressure increase their cognitive effort and vigilance to detect fraud and error. As the authors find evidence that culture moderates accountability pressure and as accountability affects scepticism, they add to the literature suggesting that culture can influence professional scepticism.


Cancer cells communicate with the environment through delivery of surface proteins, release of soluble factors (growth factors and cytokines), and sophisticated nanovehicles (exosomes) for establishment of invasive tumor growth. This communication occurs in part through constitutive exocytosis, regulated exocytosis, or release of intraluminal vesicles, and is modulated by small Rab GTPases, the master regulators of vesicle traffic. We studied Rab GTPases implicated in regulated exocytosis and showed a unique role for Rab27B in invasive tumor growth. Emerging evidence indicates that various exocytic routes are implemented by cancer cells to relay crucial information for fostering growth, migration, and matrix degradation.


Objective Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. Method 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. Results Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1–4 Hz) oscillations during the tolerance phase; in high-alpha (10–12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8–10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5–20 Hz) during the posttest phase and Gamma (28.5–45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. Conclusions These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes.


Suicide is a violent conduct causing one-self's death, and as such is one of the most complex phenomena of human behaviour. Suicide-note analyses have shown efficacy to comprehensively understand suicidal behaviour, but have been unfrequently conducted in Latin-America. The present study explored affective mobilization in the moments prior to the suicidal acts through an analysis of 203 of suicide notes from completed suicides in Chile (2010 – 2012). Interpretation was conducted according to Grounded Theory with the methods of constant comparison and theoretical saturation. The findings showed mainly positive affection, negative affection, depressive affection, and despair. It was concluded that interpersonal problems and emerging affections constituted crucial elements to understand suicidal behaviour.