Currently, the Internet and Mobile technology platforms have gained a lot of popularity in the Nigerian context. Many businesses are seizing the opportunity provided by these platforms to market their goods and services in what is termed 'e-marketing'. E-Marketing opportunities on these platforms include facebook marketing, twitter marketing, google marketing, whatsapp marketing, youtube marketing, marketing through personal blogs, sms marketing and email marketing, among others. Although these marketing avenues have been engaged by many businesses even with scarce financial resources, the result has been that of little or no corresponding effect on their profit margins. There is therefore the need to predict customer behaviour as regards these marketing avenues so that businesses can know which ones to engage for their marketing activities. This study is therefore aimed at understanding and predicting customer behaviour through correlation analysis and classification techniques in data mining respectively. The results obtained will enable the business community gain an understanding of customer behaviours and engagements on these platforms. Furthermore, the loss on marketing investments by businesses will be minimized leading to increase in business profit margins as businesses make target marketing through the stated channels efficiently.


In this paper, a new technique for testing the interconnects of an arbitrary design mapped into an FPGA is presented. In this technique, only the configuration of logic blocks used in the design is changed. The test vector and configuration generation problem is systematically converted to a satisfiability (SAT) problem, and state of the art SAT-solvers are exploited for test configuration generation. Experimental results on various benchmark circuits show that only two test configurations are required to test for all bridging faults, achieving 100% fault coverage, with respect to the fault list.


The aim of this study was to examine the experience, knowledge and attitude to mandatory reports of mistreatments amongst first line managers and assistance nurses in municipal elderly care. The following questions were at the center of the analysis: how do the different professional groups view having to report their own organization? How can various factors affect the mandatory reporting of mistreatments? What knowledge do the different professional groups have of mistreatments and mandatory reporting? A qualitative research method was used to examine these questions in the form of semi structured interviews and a small document study. The interviews were carried out with assistance nurses and first line manages in elder care, we interviewed four respondents from both professional groups. The interviews were then transcribed and coded with help of a content analysis. We have used Berger and Luckmanns theories about institutionalization when analyzing our results. We have also used Lipskys theory about street-level bureaucracy. The analysis is structured around themes and analyzed based on previous research and the above said theories. Our results show that there is a struggle amongst the both first line managers and assistance nurses to fully comprehend the complexity of mandatory reporting of mistreatments and that it's often hard to draw the line between mandatory reporting of mistreatments and other less severe reporting's such as deviation reports. Further, we have concluded that there is a fear amongst assistance nurses of reporting. Primarily because of a belief that reprisals, first and foremost from colleagues, will follow. We have also concluded that the workplace often seems to be characterized by a normative system in which loyalty and silence are common elements which may inhibit reporting.Key words: mandatory reporting of mistreatments, knowledge, attitudes, experience, elder care. Nyckelord: lex Sarah, kunskap, installning, erfarenhet, aldreomsorg.


A new potential quality assurance (QA) method is explored for clinical electron beams and clinical proton beams based on imaging and measuring Cerenkov light. A simulation was performed of the deposited energy and of Cerenkov production in water using Geant4. Monte Carlo simulation was used to predict the measured light distribution around the water phantom, to reproduce Cerenkov images and to find the relation between deposited energy and Cerenkov production. The camera was modelled as a pinhole camera in Geant4, to attempt to reproduce Cerenkov images. The potential of using a standard commercial camera to image Cerenkov light generated from electrons in water for fast QA measurement of a clinical electron beam was explored and compared to ionization chamber measurements. The new method was found to be linear with dose and independent of dose rate (to within 3%). The uncorrected practical range measured using Cerenkov images was found to overestimate the actual value by 3 mm in the worst case. The field size measurements underestimated the field sizes at the edges by 5% without applying any correction factor. Still, the measured field size could be used to monitor relative changes in the beam profile. Finally, the beam-direction profile measurements were independent of the field size within 2%. We found that imaging Cerenkov emission from a breast phantom during electron irradiation could be a suitable tool to monitor the dose and the dose rate consistency with high precision and short-term repeatability better than 3% except when measuring very low doses. Cerenkov light measurements were linear with dose and independent of dose rate. The maximum light intensity occurred at an angle of 45.0°. We were unable to identify the regions of the phantom with higher scattering and absorption properties, designed to mimic diseased tissues using images of Cerenkov emission of an optical breast phantom. We found that the Cerenkov light emissions in proton therapy can be divided into two distinct mechanisms: a fast component due to prompt gamma interactions (99.13%) and neutron interactions (0.87%), and a slow component due to radioactive decay. The simulated depth distribution of the Cerenkov emission shows a strong relation with the depth distribution of the induced radioactive isotopes, which emit positrons. The fast component was found to be linear with dose and independent of dose rate, while the slow component increases non- linearly with dose and is highly dependent on dose rate. Imaging Cerenkov light during electron radiotherapy or proton therapy could be used as a very quick routine QA tool.


Adjustable balancers are useful in applications where rotational imbalance is frequently varied. For example, in media level servo track writers used in the hard disk drive industry, a set of blank disks is loaded on a spindle motor for the purpose of servo writing. Since servo writing is performed at high speeds, imbalance introduced by disks and spacers results in significant vibrations that can affect the quality of the servo writing process. This paper proposes a new configuration of adjustable balancer that enables to compensate for rotational imbalance each time a new set of blank disks is loaded into the servo track writing machine. The adjustable balancer is ring shaped with a number of grooves displaced around axis of rotation. Steel balls are placed inside the grooves and held by permanent magnets. Imbalance compensation is achieved by electromagnetically activated release of the steel balls. The main advantage of the proposed configuration is its large compensation range. Presented three-dimensional finite-element analysis results and experimental results demonstrate and prove the effectiveness of this novel configuration.


Orthostatic instability is one of the main consequences of weightlessness or gravity challenge and plays as well a crucial role in public health, being one of the most frequent disease of aging. Therefore, the assessment of effective countermeasures, or even the possibility to predict, and thus prevent orthostatic instability is of great importance. Heat stress affects orthostatic stability and may lead to impaired consciousness and decrease in cerebral perfusion, specifically during the exposure to G-forces. Conversely, peripheral cooling can prevent orthostatic intolerance – even in normothermic healthy subjects. Indicators of peripheral vasodilation, as elevated skin surface temperatures, may mirror blood decentralization and an increased risk of orthostatic instability. Therefore, the aim of this study was to quantify orthostatic instability risk, by assessing in 20 fighter jet pilot candidates' cutaneous limb temperatures, with respect to the occurrence of G-force-induced almost loss of consciousness (ALOC), before and during exposure to a push-pull maneuver, i.e., head-down tilt, combined with lower body negative pressure. Peripheral skin temperatures from the upper and lower (both proximal and distal) extremities and core body temperature via heat-flux approach (i.e., the Double Sensor), were continuously measured before and during the maneuver. The 55% of subjects that suffered an ALOC during the procedure had higher upper arm and thigh temperatures at baseline compared to the 45% that remained stable. No difference in baseline core body temperature and distal limbs (both upper and lower) skin temperatures were found between the two groups. Therefore, peripheral skin temperature data could be considered a predicting factor for ALOC, prior to rapid onset acceleration. Moreover, these findings could also find applications in patient care settings such as in intensive care units.


This paper investigates the assessment of the first-ever proposals for accreditation of professional doctorates in Brazil. This modality of course was implemented in the country in 1998 and was designed to bridge the gap between academia and the productive sector, further integrating scientific research and societal needs. At first, the modality was restricted to the master's level, and only in 2017 new legislation authorised institutions to submit professional doctorate proposals to CAPES: the Brazilian agency in charge of accrediting graduate education. By May 2019, 30 new courses were approved, and this research analysed the evaluation reports of all of the 135 proposals initially submitted, in order to identify the criteria used to either or not accredit the courses. From the coding of such reports, it was also possible to map what the agency expects to see in successful proposals, as well as to ascertain if the evaluation process has been conducted coherently and consistently across different fields. With that, this paper can also be seen as a contribution to Brazilian academia in the design of future professional doctorate proposals.


BALOIAN, B.E., Anger in the Old Testament (American University Studies VII/99; New York: Peter Lang, 1992), pp. 225. Cloth, £21.00. ISBN 0-8204-1514-6. This Claremont dissertation charts human anger in the OT, then divine anger, then the correlation of the two, concluding with a 'theological vantage point' (and an Excursus on jealousy). Human anger is occasionally appropriate, e.g. in response to injustice. It is to be controlled, not suppressed. Divine anger is not just emotion, it is efficacious, usually upon a nation; it is prompted by injustice, and expresses love. Theologically, God's anger was good for Israel. The argument seems at times to


A systematic investigation of the ground-state geometries and stabilities of clusters made by employing ab initio density-based molecular dynamics is reported. Although in the solid-state form, the 50:50 alloy takes on a B32-ordered structure, no evidence for such ordering has been seen for small clusters. Instead there is a clustering tendency of the Al atoms, and they tend to form inner clusters whose geometries are different from those of the free Al clusters. The Li and Al atoms favour a tetrahedral coordination due to the significant role of the s - p bonding of the electrons. A stability analysis based on energetics shows that the stability is enhanced in clusters where all of the Al faces have been capped by Li atoms, and this gives some remarkably interesting geometries, like the face-centred-cubic structure of .


Background: Alzheimer's disease (AD) is a leading cause of dementia in the elderly and has become a major health issue. However, a large number of genetic risk factors remain undiscovered. Methods: To identify novel risk genes and better understand the molecular pathway underlying AD, whole-exome sequencing (WES) was performed in 215 early-onset AD (EOAD) patients and 55 unrelated healthy controls of Han Chinese ethnicity. Subsequent direct sequencing was performed in 4962 individuals to validate the selected rare mutations. Computational annotation and in vitro functional studies were performed to evaluate the role of candidate mutations in EOAD and the underlying mechanisms.Results: We identified two rare missense mutations in the phosphodiesterase 11A (PDE11A) gene, resulting in p.Arg202His, and p.Leu756Gln, in individuals with EOAD. Both mutations are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation, and classified as pathogenic. Furthermore, we found significantly decreased protein levels of PDE11A in brain samples of AD patients. Expression of PDE11A variants and knockdown experiments with specific short hairpin RNA (shRNA) for PDE11A both resulted in an increase of AD-associated Tau hyperphosphorylation at T181, S404, S202, S416, S214, S396 and AT8 epitopes in vitro. PDE11A variants or PDE11A shRNA also caused increased cAMP levels, protein kinase A (PKA) activation, and cAMP response element-binding protein (CREB) phosphorylation. Additionally, pretreatment with a PKA inhibitor (H89) suppressed PDE11A mutation-induced p-Tau formation.Conclusions: Our results demonstrate that both PDE11A mutations and PDE11A knockdown increase Tau phosphorylation through the cAMP/PKA pathway, suggesting that PDE11A is a novel risk gene for AD. This study provides insight into the involvement of Tau phosphorylation via the cAMP/PKA pathway in EOAD pathogenesis and provides a potential new target for intervention.


The master sinter curve (MSC) is an empirical model used to predict the density of a part after being sintered. The model is typically applied to components that undergo isotropic shrinkage. Parts manufactured using binder jetting additive manufacturing (BJAM) are known to have nonuniform powder systems and high levels of anisotropy. This work explores the application of the master sinter curve to components made by BJAM. Cylindrical samples were manufactured with the long axis parallel (vertical), perpendicular (horizontal), and 45 deg to the printing direction. A bimodal blend of titanium powder (0–45  µm and 106–150 µm) was used to make samples with consistent green densities (ranging from 47.2% to 52.3%) between the different orientations. Samples were then sintered at heating rates of 1, 3, and 5 °C/min to a maximum of 1400 °C. After sintering, the samples showed significant variation between the different orientations, with vertical samples on average 7.6 ± 2.98% and 4.7 ± 1.20% denser than the horizontal and the 45 deg samples, respectively. The calculated apparent activation energies for sintering were within the same range for all orientations, 200–260 kJ/mol for vertical and 45 deg, and 140–260 kJ/mol for horizontal samples. Validation sinter runs showed that the density prediction errors of the master sinter curves were between 0.9% and 4.3%. This work shows that the master sinter curve can be applied to predict the sintered density of components manufactured by binder jetting additive manufacturing.


Objective:To evaluate the feasibility and efficacy of sequential neoadjuvant chemotherapy, chemoradiation, and surgery in patients with locally advanced esophageal cancer. Patients and Methods:There were 29 patients who received paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2 2 weeks apart. Two weeks later, patients received cisplatin 75 mg/m2 and 5-fluorouracil (5-FU) 1000 mg/m2/d continuous infusion for 4 days with concurrent radiotherapy in 15 fractions to a total dose of 4000 cGy. After 6 weeks, cisplatin and 5-FU were repeated at the above doses. After 4 to 6 weeks, patients were restaged and underwent surgical resection. Results:All 29 patients completed the prescribed gemcitabine, paclitaxel, and radiation therapy. Febrile neutropenia occurred in 1 patient and 4 patients received growth factor support. After neoadjuvant treatment, 1 patient refused surgery, 23 underwent R0 resection (82%), while 5 developed progressive disease. Four patients developed anastomotic leaks (17%). Four patients had complete pathologic responses (14%) and 4 (14%) had only residual microscopic disease. Nine patients remain alive at a median follow-up of 48 months. Three-year survival for the entire cohort was 36%. Conclusion:This regimen was associated with a high rate of compliance and induction therapy had an acceptable toxicity profile. The R0 resection rate and 3-year survival data are similar to recently reported studies. While active, gemcitabine and paclitaxel induction therapy was associated with an increased rate of postoperative complications, but no increase in survival. Patterns of failure continue to demonstrate the need for regimens incorporating greater emphasis on systemic therapy for locally advanced esophageal cancer.


With the conversion of Constantine in 312, Christianity began a period of political and cultural dominance that it would enjoy until the twentieth century. Jacob Neusner contradicts the prevailing view that following Christianity's ascendancy, Judaism continued to evolve in isolation. He argues that because of the political need to defend its claims to religious authenticity, Judaism was forced to review itself in the context of a triumphant Christianity. The definition of issues long discussed in Judaism the meaning of history, the coming of the Messiah, and the political identity of Israel became of immediate and urgent concern to both parties. What emerged was a polemical dialogue between Christian and Jewish teachers that was unprecedented. In a close analysis of texts by the Christian theologians Eusebius, Aphrahat, and Chrysostom on one hand, and of the central Jewish works the Talmud of the Land of Israel, the Genesis Rabbah, and the Leviticus Rabbah on the other, Neusner finds that both religious groups turned to the same corpus of Hebrew scripture to examine the same fundamental issues. Eusebius and Genesis Rabbah both address the issue of history, Chrysostom and the Talmud the issue of the Messiah, and Aphrahat and Leviticus Rabbah the issue of Israel. As Neusner demonstrates, the conclusions drawn shaped the dialogue between the two religions for the rest of their shared history in the West."


GMR sensors are increasingly used for magnetic surface inspection due to their high sensitivity and high spatial resolution. In case of simple planar or cylindrical shaped components, the GMR-based inspection procedure can be automated easily. In order to reduce the inspection time we present a GMR-based NDT-system consisting of a yoke and a coil as a local magnetization unit. This way the global magnetization step and, if necessary, the corresponding demagnetization cycle can be avoided reducing the number of working steps. Using a local probe we measured plates, bearings, and rails, each of which containing real fatigue cracks and reference artificial cracks of different depths and orientations. Cracks with a depth of 40 μm could be resolved with a signalto-noise ratio of about 20. A reduction of the measuring time can be obtained using a sensor array. We present an optimized sensor array for nondestructive testing application, where gradiometric arranged GMR layers were fabricated on a board with up to 48 GMR sensors. Each sensor detects the vertical field gradient. In our example the baseline was chosen to be 250 μm which efficiently suppress external background fields without losing sensitivity for the detection of surface breaking defects.


The influence of space flight factors on optomotor reactions and optokinetic resistance of 17 cosmonauts after prolonged (75 and 185 days) and short-term (4, 7, 14 days) flights is discussed.


ABSTRACT Online risks and harms, including cyber-bullying, trolling, revenge porn and digital harassment, are an everyday reality in many young people's lives. Educators are increasingly being called upon to address these concerns but are not adequately equipped to do so. In this article the case is made for a new educational model for cyber-flourishing. The model is constructed through a pragmatic approach to moral theory, adopting the central tenets of deontology, utilitarianism and virtue ethics, and showing how these can be integrated and put to work by teachers to tackle online harms. The model is comprised of three core components, cyber-rules, cyber-wisdom and cyber-flourishing, and each is explained in detail in the article. Cyber-rules must be put in place by schools to provide the foundations for the cultivation of character and cyber-wisdom. Cyber-wisdom is the individual quality of doing the right thing, at the right time, especially when no one is looking. Cyber-flourishing is defined as authentic happiness that comes from living morally in the online world, and is the utility value that we should all strive for. The article concludes by outlining nine educational practices that demonstrate how teachers can adopt and implement the model in their schools. The model is the first attempt in the world to integrate moral theory into an educational model that provides an overarching and whole-school approach to tackling pressing everyday online concerns.


The control of propagating cracks in structures first requires an understanding of the interrelationships of microstructure, fractographic features, dynamic stress intensity factor, and crack velocity in materials. Conventional techniques for measuring crack velocity suffer in varying degrees from imprecision, excessively stringent synchronization requirements or poor resolution due to data compression on a single oscilloscope sweep. A new instrumentation concept has evolved from consideration of the advantages and limitations of earlier techniques. High-speed digital data processing techniques are used to measure time of sequential events 300 ns apart to an accuracy of ′ 50 ns. Temporary storage, high-speed sampling, and a 3:1 multiplexing scheme have been combined with a random access memory structure to enable recording times of as many as three simultaneous events per microsecond. Special templates have been designed to vapor deposit on sample metallic propagation grid configurations that take full advantage of the electronic capabilities of the system. These have 250-μm slits precisely spaced 5 deg apart in radial arrays and 1 mm apart in parallel arrays. Applications to fast fracture, crack branching, fatigue cracking, and stress-corrosion cracking are discussed.


Assessing the semantic similarity of terms is identified is an important step in many real world applications ranging from information retrieval systems to Geographic Information Science (GIS). In geographic information science and semantics, the computation of semantic similarity and relatedness is widely recognized as key to supporting a vast number of tasks in information integration and retrieval. By contrast, the role of them has been largely ignored in this context. In this paper, the notion of geographic semantic relatedness and similarity is discussed and their impotence is highlighted in task of Geographic Information System. Subsequently, various measures conducted in this filed for computing semantic relatedness of geographic terms are reviewed and their potentials and drawbacks are mentioned. The article concludes by comparing the similarity measures and giving general advice how to choose an appropriate semantic similarity and relatedness measure. Advantages and disadvantages point to their suitability for different tasks.


This work describes a method for calculating pressure fields from temperature and velocity data in non-adiabatic compressible flows, such as the flow around a cooled turbine vane. Prior studies have demonstrated the ability to use particle image velocimetry methods to estimate the pressure gradient in the momentum equation, which is subsequently integrated to produce pressure fields. Due to changes in total temperature for non-adiabatic compressible flows, pressure fields cannot be computed from velocity measurements alone and temperature data must also be provided. In this work, a benchmarked steady 3D RANS simulation is used to generate velocity, temperature, and pressure fields in the transonic flow around a high-pressure turbine inlet guide vane. A procedure for solving the momentum equation and integrating for pressure is developed for non-adiabatic flows. Error is assessed by comparing calculated pressure to CFD predicted pressure, and the effects of PIV spatial resolution and measurement error are considered. The accuracy of the method on non-adiabatic flows is assessed using a vane with extensive film cooling. A clear benefit of incorporating temperature measurements in the pressure determination method is demonstrated, offering opportunities for deeper understanding of aerodynamic losses and entropy generation in cooled turbine flowfields.


This study adds a microeconomic perspective to the discussion on ethnic diversity and economic performance in developing countries by investigating the motivation for intra-ethnicity marriage in rural Sub-Saharan Africa. Specifically, the paper proposes that ethnic similarity between spouses enhances economic outcomes through a shared agricultural production technology. Furthermore, the framework suggests that the probability of marriage within the same ethnic group is positively related to the size of the group due to frictions in the marriage market: Search costs for co-ethnic spouses are larger the smaller the group. The theoretical propositions are supported using Ethiopian rural household data by demonstrating that inter-ethnicity marriage of the household head has adverse implications for family income. The negative effect is robust to controlling for lagged income and initial conditions, present when investigating the link with changes in family wealth, and persists in additional sensitivity checks.


This chapter outlines in four sections the recent development of the study of the cultural industries, the challenges that have shaped it, and what the consequences of the growth and development of the cultural industries are. We begin by positioning the cultural industries within academic debate s discuss how they have been conceptualised. The second section is concerned with the problems of defining the cultural industries. In the third section we examine the range of secondary impacts, and in the fourth section we consider the primary impacts of the cultural industries under five headings: production process, the speed of circulation, intermediation, project based firms, and spatial clustering.


Despite a long history of study, the mechanisms underlying the geographical patterns of species richness are still controversial. Patterns and determinants of species richness are well-known to vary with spatial scale. However, most studies on the effects of scale have focused on grain size whereas the quantitative effects of geographical extent are rarely tested. Here, using distribution maps of 11 405 woody species found in China and associated environmental data to the domain, we investigated the influence of geographical extent on the determinants of species richness patterns. Our results revealed consistent extent dependence of all species, narrow- and wide-ranged species: with the expansion of geographical extents, the explanatory power of climate (i.e. environmental energy, water availability and climatic seasonality) increased, while the explanatory power of habitat heterogeneity and human activities decreased. Although the primary determinant of species richness patterns varied significantly at small to meso-geographical extent, we showed that species richness was predominantly determined by environmental energy at large extent. Our findings indicate that differences in geographical extent may have led to the controversies regarding the primary determinants of richness patterns in previous studies, and that a multi-scale perspective not only with regard to grain-size but also extent is likely to shed new light on this old debate of what determines richness patterns.


"Software security" often evokes negative feelings amongst software developers because this term is associated with additional programming effort, uncertainty and road blocker activity on rapid development and release cycles. The Secure DevOps movement attempts to combat the toxic environment surrounding software security by shifting the paradigm from following rules and guidelines to creatively determining solutions for tough security problems Taschner, 2015. Secure software should be focused on a proactive approach that limits the attack surface and produces reliable software. Secure DevOps developers want their software to bend but not break, which means the software absorbs attacks and continues to function. The burgeoning concepts of DevOps include a number of concepts that can be applied to increase the security of developed applications. Applying these and other DevOps principles can have a big impact on creating an environment that is resilient and secure. Specifically, this paper clearly explains how to address security concerns in the early stages of the development lifecycle and leverage that knowledge throughout the SDLC.


The meningiomas are justly considered to be among those intracranial tumours most amenable to treatment, and if the difficulties, often formidable, attending their removal can be overcome, there is good prospect of a permanent cure. However, in occasional cases, late recurrences do take place, even after resections appearing entirely satisfactory to the surgeon responsible. This is not a common misfortune, but neither is it rare enough to be negligible. Considerable interest attaches to the tumours which recur after seemingly adequate treatment. They present important practical problems in prophylaxis and in management. And they are most instructive as studies in the biology of the meningiomas generally. Most neurosurgeons have experienced the disappointment of such recurrences. Horsley (1893), Ballance (1907), and Krause (1910-12), while stressing the innocence of the tumours they designated fibromas, endotheliomas, or dural sarcomas, all mention their occasional unexpected recurrence. Initially, little importance was attached to these recurrences, but as neurosurgical technique improved and the number of survivals increased, they attracted more attention. Craig, in 1927, first emphasized the variations in the natural history of the meningiomas, and separated a group whose histology and behaviour he considered frankly malignant. Taylor (1928) also challenged contemporary belief in the innocence of the meningiomas. It was, however, in the great monograph of Cushing (1938) that the behaviour of the meningiomas and their disposition to recur were most fully discussed. Cushing apparently began his surgical career with the conviction that the meningiomas are highly benign tumours: he ultimately came to treat them with the greatest respect, as prone to infiltrate locally and to recur from such infiltrations. In 43 of his 295 cases, reoperation for " actual or symptomatic" recurrence was necessary, and 76 patients died at home with incompletely removed tumours. Cushing unfortunately does not state the incidence of recurrence after operations which had appeared to him as total removals: but analysis of his tabulated cases suggests that it was not less than 15%. He and Eisenhardt presented a complex histological classification, which was specifically intended as a guide to the biological behaviour of the tumours, but they nevertheless recognized the limitations of the histological assessment. This monograph remains the prime source for any study of the meningiomas. Since its publication, there have been a number of reports on the modern treatment of meningiomas; in most of these the development of recurrence is mentioned. There has been at least one study devoted solely to this problem (Volynkin, 1955). Much has been written on the pathology of the meningiomas, and especially on their occasional malignancy. A review of the large body of literature suggests, however, that there is still difference of opinion on several questions of fundamental importance. (1) There is no agreement on the frequency or significance of recurrence. Very few contemporary surgeons have given the incidence of recurrence in their material. Olivecrona (Olivecrona, 1947; Hoessly and Olivecrona, 1955) thought that with his parasagittal meningiomas the recurrence rate was under 10%; his figures are, however, admittedly incomplete, since they do not comprehend patients dying at home. Grant (1954) reported 13 delayed deaths due to tumour growth in 219 cases, all after " incomplete removals ". He refers to these fatalities as deaths from recurrence, and very properly, since one may speak of a symptomatic recurrence even after an operation known to have been incomplete. But it is not possible to determine from his account whether these " incomplete removals " had been recognized as such initially, or whether they had appeared complete resections at the original operation. This is a crucial distinction. The same uncertainty vitiates (for this particular purpose) the report of Horrax and Strain (1952), who mention nine fatal recurrences in 168 cases. Moreover, in neither 22 P rocted by coright.


Worldwide, more than 1 million people develop colorectal cancer (CRC) annually. CRC is a major health problem in the Western world and the second most common cause of cancer mortality. To improve performance, the role of chemotherapy for CRC has increased dramatically over the last decade. The vast majority of CRC patients now receive chemotherapy with multiple agents that are currently approved for the treatment in the appropriate setting [1]. However, it is a complex process to select the optimal chemotherapy for each patient and practice evidence gap is still a problem. Some guidelines for the treatment of CRC have been developed to promote the standardization of CRC treatment. Postoperative, or "adjuvant," systemic therapy has become standard for stage III colon cancer. Adjuvant therapy should also be strongly considered in stage II patients. It is generally recommended for any medically fit patient with stage II cancer with unfavorable factors. The hypothesis that the antitumor activity of the combination agent, including oxaliplatin, irinotecan, bevacizumab, cetuximab in metastatic cure rates, would result in increased adjuvant proved to be often wrong. Although new drug development takes years, targeted drug use can occur more quickly with advanced tests and will be a focus of future work. In addition, efforts will focus on identifying biomarkers that predict response to systemic therapy so that tailored therapy can be initiated. The future of oncology will come with the better understand‐ ing of the biology and genetics of the tumor and its host. This will help to develop tailored approach to the patients, including more specific systemic therapy, aimed at molecular targets of the malignant tumor, thus reducing the negative effects. At that time, the treatment of oncological diseases will experience a new era, comparable to the introduction of antibiotics.


Abstract This research investigates postage stamps as a communication design medium that has a key role in the construction of national gendered commemoration. By examining the commemorative depiction of women on Israeli postage stamps, we analyze approaches to miniaturization and discuss graphic design's implications for the visual articulation of gender within national culture. We further discuss the impact of technological transformations and digitization processes on postage stamp design. We apply social semiotic methodologies, archival research, and interviews with the designers, presenting new findings pertaining to research for design. As such, the present research expands our understanding of small-scale communication design for smartphones, icons, and logos.


There has been in the past ten to fifteen years a surge of activity concerning the cohomology of semi-direct product groups of the form $\mathbb{Z}^{n}\rtimes$G with G finite. A problem first stated by Adem-Ge-Pan-Petrosyan asks for suitable conditions for the Lyndon-Hochschild-Serre Spectral Sequence associated to this group extension to collapse at second page of the Lyndon-Hochschild-Serre spectral sequence. In this thesis we use facts from integer representation theory to reduce this problem to only considering representatives from each genus of representations, and establish techniques for constructing new examples in which the spectral sequence collapses.


Notwithstanding several neurotransmission systems are frequently related to memory formation; forgetting process and neurotransmission systems or their transporters; the role of c-aminobutyric acid (GAT1), glutamate (EACC1), dopamine (DAT) and serotonin (SERT) is poorly understood. Hence, in this paper western-blot analysis was used to evaluate expression of GAT1, EAAC1, DAT and SERT during forgetting in trained and untrained rats treated with the selective serotonin transporter inhibitor fluoxetine, the amnesic drug d-methamphetamine (METH) and fluoxetine plus METH. Transporters expression was determined in the hippocampus (HIP), prefrontal cortex (PFC) and striatum (STR). Results indicated that forgetting of Pavlovian/instrumental autoshaping was associated to up-regulation of GAT1 (PFC and HIP) and DAT (PFC) while SERT (HIP) was down-regulated; no-changes were observed in striatum. Methamphetamine administration did not affect forgetting at 216 h post-training but up-regulated hippocampal DAT and EACC, prefrontal cortex DAT and striatal GAT1 or EACC1. Fluoxetine alone prevented forgetting, which was associated to striatal GAT1 and hippocampal DAT up-regulation, but prefrontal cortex GAT1 down-regulation. Fluoxetine plus METH administration was also able to prevent forgetting, which was associated to hippocampal DAT, prefrontal cortex SERT and striatal GAT1, DAT or SERT up-regulation, but prefrontal cortex GAT1 down-regulation. Together these data show that forgetting provokes primarily hippocampal and prefrontal cortex transporters changes; forgetting represent a behavioral process hardly modifiable and its prevention could causes different transporters expression patterns.


Abstract. This paper provides an introduction to the concepts of water security including not only the risks to human wellbeing posed by floods and droughts, but also the threats of inadequate supply of water in both quantity and quality for food production, human health, energy and industrial production, and for the natural ecosystems on which life depends. The overall setting is one of constant change in all aspects of Earth systems. Hydrological systems (processes and regimes) are changing, resulting from varying and changing precipitation and energy inputs, changes in surface covers, mining of groundwater resources, and storage and diversions by dams and infrastructures. Changes in social, political and economic conditions include population and demographic shifts, political realignments, changes in financial systems and in trade patterns. There is an urgent need to address hydrological and social changes simultaneously and in combination rather than as separate entities, and thus the need to develop the approach of 'socio-hydrology'. All aspects of water security, including the responses of both UNESCO and the International Association of Hydrological Sciences (IAHS) to the concepts of socio-hydrology, are examined in detailed papers within the volume titled Hydrological Sciences and Water Security: Past, Present and Future.


Long-distance race car drivers are classified as athletes. The sport is physically and mentally demanding, requiring long hours of practice. Therefore, optimal dietary intake is essential for health and performance of the athlete. The aim of the study was to evaluate dietary intake and to compare the data with dietary recommendations for athletes and for the general adult population according to the German Nutrition Society (DGE). A 24-h dietary recall during a competition preparation phase was obtained from 16 male race car drivers (28.3 ± 6.1 years, body mass index (BMI) of 22.9 ± 2.3 kg/m2). The mean intake of energy, nutrients, water and alcohol was recorded. The mean energy, vitamin B2, vitamin E, folate, fiber, calcium, water and alcohol intake were 2124 ± 814 kcal/day, 1.3 ± 0.5 mg/day, 12.5 ± 9.5 mg/day, 231.0 ± 90.9 ug/day, 21.4 ± 9.4 g/day, 1104 ± 764 mg/day, 3309 ± 1522 mL/day and 0.8 ± 2.5 mL/day respectively. Our study indicated that many of the nutrients studied, including energy and carbohydrate, were below the recommended dietary intake for both athletes and the DGE.


In milling operations, cutting edge impacts due to the interaction between the cutter and the workpiece excite vibrations. It is possible to distinguish between free, forced and self-excited vibrations. Chatter is a self-excited vibration that can occur in machining processes, and is considered to be a common limitation of productivity and quality. Stability lobes diagrams (SLDs) show the frontier between chatter-free milling operations, i.e. stable dominated by forced vibrations, and operations with chatter, i.e. unstable. These diagrams are usually obtained from impact hammer testing. However, this method requires trained personnel with advanced knowledge and it is not easily applied in engineering studies or operator training. This paper presents an experimental method that allows engineering students and operators-in-training to observe the chatter phenomenon and to distinguish between forced and chatter vibrations and identify process stability diagrams.


With rapidly evolving internet technologies and emerging tools, sports related videos generated online are increasing at an unprecedentedly fast pace. To automate sports video editing/highlight generation process, a key task is to precisely recognize and locate the events in the long untrimmed videos. In this tech report, we present a two-stage paradigm to detect what and when events happen in soccer broadcast videos. Specifically, we fine-tune multiple action recognition models on soccer data to extract high-level semantic features, and design a transformer based temporal detection module to locate the target events. This approach achieved the state-of-the-art performance in both two tasks, i.e., action spotting and replay grounding, in the SoccerNet-v2 Challenge, under CVPR 2021 ActivityNet workshop. Our soccer embedding features are released at https://github.com/baidu-research/vidpress-sports. By sharing these features with the broader community, we hope to accelerate the research into soccer video understanding.


Internationalisation of the curriculum has created changes to the traditional curriculum but little attention in research has been paid to the student perspective on these changes, and how they experience them. This paper aims to fill the gap by reporting on the findings of graduate students' perceptions of the internationalisation of the curriculum at Makerere University in Uganda. This study adopted a sequential explanatory survey study in which we collected both quantitative and qualitative data from a sample of 180 graduate students. The findings showed that the majority of the respondents agreed that their curricula had an international dimension. This was commonly seen by graduate students in terms of international academic staff, international students, travel abroad programmes for students, courses with an international focus, comparative studies and focus on ICTs. The participants voiced concerns about logistical constraints and the universality of knowledge. These findings reinforced the earlier research that proposed that the above aspects are critical in the IoC and can act as benchmarks to guide further work in the direction of the university's internationalisation agenda. No earlier works had similar results, at least in the context of the Global South where this study was conducted. Further studies need to involve other actors in higher education to explore more fully the notion of IoC to explain better the basis of students' perceptions and experiences of IoC reported in this study.


Dysphagia is common but may be underreported. Specific symptoms, rather than their perceived location, should guide the initial evaluation and imaging. Obstructive symptoms that seem to originate in the throat or neck may actually be caused by distal esophageal lesions. Oropharyngeal dysphagia manifests as difficulty initiating swallowing, coughing, choking, or aspiration, and it is most commonly caused by chronic neurologic conditions such as stroke, Parkinson disease, or dementia. Symptoms should be thoroughly evaluated because of the risk of aspiration. Patients with esophageal dysphagia may report a sensation of food getting stuck after swallowing. This condition is most commonly caused by gastroesophageal reflux disease and functional esophageal disorders. Eosinophilic esophagitis is triggered by food allergens and is increasingly prevalent; esophageal biopsies should be performed to make the diagnosis. Esophageal motility disorders such as achalasia are relatively rare and may be overdiagnosed. Opioid-induced esophageal dysfunction is becoming more common. Esophagogastroduodenoscopy is recommended for the initial evaluation of esophageal dysphagia, with barium esophagography as an adjunct. Esophageal cancer and other serious conditions have a low prevalence, and testing in low-risk patients may be deferred while a four-week trial of acid-suppressing therapy is undertaken. Many frail older adults with progressive neurologic disease have significant but unrecognized dysphagia, which significantly increases their risk of aspiration pneumonia and malnourishment. In these patients, the diagnosis of dysphagia should prompt a discussion about goals of care before potentially harmful interventions are considered. Speech-language pathologists and other specialists, in collaboration with family physicians, can provide structured assessments and make appropriate recommendations for safe swallowing, palliative care, or rehabilitation.


: First clinical indications of positron emission tomography (PET) were in the fields of neurology and cardiology, but oncology is the domain in which PET got its recognition as an essential diagnostic tool. Its fast diffusion as an imaging method for diagnosis and follow-up of cancer has been facilitated by the existence of a single tracer for all kinds of oncological PET explorations. Nowadays, this tracer, fluorodeoxyglucose (FDG), is so largely distributed that non oncological PET indications have emerged. For instance, PET with FDG has totally supplanted gallium-67 for the evaluation of inflammatory conditions. Another non oncological domain in which PET with FDG has kept an important clinical role is neurology. The strong local relationship between neuronal activity and cerebral glucose uptake confers to PET with FDG a primordial role in neurological conditions in which structural changes are insufficient to establish a firm diagnosis. This is the case for focal epilepsy that remains an undisputed indication of PET with FDG, and for neurodegenerative disorders, in particular those that lead to dementia for which tracers detecting amyloid and tau depositions are now available. New tracers have enlarged PET indications in oncology, in particular for cancers that are not well evaluated with FDG. Since the early clinical PET introduction, patients with brain tumours are benefiting from PET exploration with amino-acid tracers, in particular for therapeutic tumour targeting. The recent development of tracers for neuroendocrine and prostatic cancers has opened a new field of applications for PET, linked to innovative radiotherapeutic approaches.


Strategic controlling has become an imperative in business planning and determining company's long-term goals. Companies use different managerial tools in their planning process in order to determine possible threats and opportunities in their business environment. The goal of the paper is to present a case study of one pharmaceutical Croatian company using the model INDUSTRUCT, which is utilized for analysing industrial environment, which is, develop based on the Porter's five forces model. Although recent research results show that companies in Croatia use more often operational tools in their business rather than strategic tools this model shows the simplicity of its use and easiness of analyse. Focus of the research is highly competitive rivalry in pharmaceutical industry characterized with the big threats from supplier, buyers, substitutes, as well as newcomers. In such highly competitive industry, companies must constantly rethink their strategies and use tools that will help them detect threats and opportunities hiding in their environment.


The clinical translation of Fourier transform infrared (FT-IR) microspectroscopy in pathology will require bringing this technique as close as possible to standard practice in pathology departments. An important step is sample preparation for both FT-IR microspectroscopy and pathology. This should entail minimal disruption of standard clinical practice while achieving good quality FT-IR spectral data. In fact, the recently described possibility of obtaining FT-IR spectra of cells placed on glass substrates brings FT-IR microspectroscopy closer to a clinical application. We have now furthered this work in order to identify two different types of lung cancer cells placed on glass coverslips. Two types of sample preparation which are widely used in pathology, cytospin and smear, have been used. Samples were fixed with either methanol, used in pathology, or formalin (4% paraformaldehyde) used widely in spectroscopy. Fixation with methanol (alcohol-based fixative) removed lipids from cells causing a decrease in intensity of the peaks at 2850 cm−1 and 2920 cm−1. Nevertheless, we show for the first time that using either type of sample preparation and fixation on thin glass coverslips allowed to differentiate between two different types of lung cancer cells using either the lipid region or the fingerprint region ranging from 1800 cm−1 to 1350 cm−1. We believe that formalin-fixed cytospin samples would be preferred to study cells on thin coverslips using FT-IR microspectroscopy. This work presents a clear indication for future advances in clinical assessment of samples within pathology units to gain a deeper understanding of cells/tissues under investigation.


Having been working for some time past at the Cretaceous Fishes, my interest has been especially centred in the group of the Edaphodontidæ; for the specimens belonging to this group, which have been brought to light within the last few years, have much enlarged our knowledge of these peculiar forms of fossil fishes. The general results of my examination of this group, will shortly be published; and in the present communication it is only proposed to consider two specimens from the Lower Greensand of New Zealand, which have been deposited in the British Museum by Dr. Hector. My attention was first directed to these specimens by Mr. W. Davies, of the British Museum, when I was examining the fine series of Chimæroid jaws now in the national collection. One of these New-Zealand specimens is the right mandible of a species of Ischyodus already known to us from the Gault of Folkestone; and the second is a small right maxilla, which is altogether new and appears to be generically distinct from any of the fossil forms hitherto described. Before considering the peculiarities of the mandible, it will be necessary to enter into some explanation and description of the species to which it is referred. It appears that, the late Prof. Agassiz, some years ago, saw in the Earl of Enniskillen's collection of fossil fishes, a Chimæroid mandible from the Gault of Folkestone, which he named, in manuscript, Chim0œra brevirostris. Subsequently, in his ' Poissons Fossfles' (1843), he alluded to this specimen


A multiplexing communications channel is considered. The network stations share the channel on a time-division multiple-access (TDMA) basis or by using a slotted frequency-division multiple-access (FDMA) scheme. Messages are categorized by their differing priorities. Two service disciplines are considered: nonpreemptive and preemptive-resume. A discrete-time priority queuing system is introduced and investigated. Message-delay distributions are obtained for priority and ordinary messages in a two-class system model, under each service discipline. Next, delay analysis for a p-class model is carried out. The results are then applied to general, slotted, priority FDMA and TDMA schemes. >


This current work aims to determine phytochemicals, in vitro radical scavenging, and in vivo oxidative stress reduction activities of peppermint (Mentha piperita L.) ethanolic extract (PEE). The Clule method was used to determine the phytochemical content. An in vitro antioxidant with radical scavenging activity was measured using 2,2-diphenyl-1-picrylhydrazyl. An in vivo antioxidant with oxidative stress reduction was carried out for 10 days on 25 male Sprague–Dawley rats (divided into five groups). Every day, each group was given positive control, negative control, 5, 10, and 20 mg/200 gr of body weight (BW) of the extract. The blood plasma was taken for malondialdehyde analysis. A phytochemical identification of PEE revealed more compounds, such as flavonoids, alkaloids, steroids, essential oils, and tannin. PEE exhibits significant in vitro radical scavenging activity, with an IC50 value of 126.695 μg/mL. In the in vivo antioxidant with oxidative stress reduction experiments, 5 mg/200 gr BW was the most effective dose, as evidenced by a considerable drop in malondialdehyde level (0.312 nmol/mL) after and before treatment. In conclusion, PPE has the potential to be developed as a herbal antioxidant based on in vitro and in vivo test results.


Recently exosomes have attracted interest due to their potential as cancer biomarkers. We report the real time, label‐free sensing of single exosomes in serum using microtoroid optical resonators. We use this approach to assay the progression of tumors implanted in mice by specifically detecting low concentrations of tumor‐derived exosomes. Our approach measures the adsorption of individual exosomes onto a functionalized silica microtoroid by tracking changes in the optical resonant frequency of the microtoroid. When exosomes land on the microtoroid, they perturb its refractive index in the evanescent field and thus shift its resonance frequency. Through digital frequency locking, we are able to rapidly track these shifts with accuracies of better than 10 attometers (one part in 10^11). Samples taken from tumor‐implanted mice from later weeks generated larger frequency shifts than those from earlier weeks. Control samples taken from a mouse with no tumor generated no such increase in signal between subsequent weeks. Analysis of shifts from tumor-implanted mouse samples show a distribution of unitary steps, with the maximum step having a height of ~1.2 fm, corresponding to an exosome size of 44 ± 4.8 nm. This size range corresponds to that found by performing nanoparticle tracking analysis on the same samples. Our results demonstrate development towards a minimally‐invasive tumor "biopsy" that eliminates the need to find and access a tumor.


Creative cognition is important to academic performance and career success during late adolescence and adulthood. However, there is a lack of longitudinal data on whether brain structural development could predict improvements in creative thinking, and how such changes interact with other cognitive abilities to support creative performance. Here we examined longitudinal alterations of brain structure and their relation to creative cognitive ability in a sample of 159 healthy young adults who were scanned using magnetic resonance imaging 2-3 times over the course of 3 years. The most robust predictor of future creative ability was the right dorsolateral prefrontal cortex (DLPFC), which in conjunction with baseline creative capacity showed a 31% prediction rate. Longitudinal analysis revealed that slower decreases in gray matter density within left frontoparietal and right frontotemporal clusters predicted enhanced creative ability. Moreoever, the relationship between longitudinal alterations within frontal-related clusters and improved creative ability was moderated by the right DLPFC and working memory ability. We conclude that continuous goal-directed planning and accumulated knowledge are implemented in the right DLPFC and temporal areas, respectively, which in turn support longitudinal gains in creative cognitive ability.


James Frederick Ferrier was born in Edinburgh on June 16th, 1808. He was educated privately and at the Royal High School, Edinburgh. After spending two sessions at Edinburgh University, he entered Magdalen College, Oxford, where he graduated in 1831. Returning to Edinburgh, he qualified as an advocate in 1832, but devoted himself to philosophical studies, largely as a result of his close friendship with Sir William Hamilton. In 1838-9, he published An Introduction to the Philosophy of Consciousness in Blackwood's Magazine. This was followed by a number of interesting articles and reviews, chiefly on sense-perception. In 1844, Ferrier deputised for SirWilliam Hamilton in the Chair of Logic and Metaphysics at Edinburgh, and, in the following year, he became Professor of Moral Philosophy and Politica Economy in St Andrews. In 1854, he published The Institutes of Metaphysics. He died in 1864, leaving behind him a valuable course of Lectures on Greek Philosophy, which was published posthumously.


As digital system speeds increase and their sizes diminish, it becomes increasingly important to understand the mechanism of signal crosstalk (noise) in interconnections between logic elements. The worst case is when two wires run parallel for a long distance. Past literature has been unsuccessful in explaining crosstalk between parallel wires above a ground plane, because it was assumed that only one signal propagation velocity was involved. This paper proves that a signal introduced at one end of a printed wire above a ground plane in the presence of a second parallel (passive) wire must break up into two signals traveling at different velocities. The serious crosstalk implications are examined. The new terms slow crosstalk (SX), fast crosstalk (FX) and differential crosstalk (DX) are defined.


Proteins are biochemical entities consisting of one or more blocks typically folded in a 3D pattern. Each block (a polypeptide) is a single linear sequence of amino acids that are biochemically bonded together. The amino acid sequence in a protein is defined by the sequence of a gene or several genes encoded in the DNA-based genetic code. This genetic code typically uses twenty amino acids, but in certain organisms the genetic code can also include two other amino acids. After linking the amino acids during protein synthesis, each amino acid becomes a residue in a protein, which is then chemically modified, ultimately changing and defining the protein function. In this study, the authors analyze the amino acid sequence using alignment-free methods, aiming to identify structural patterns in sets of proteins and in the proteome, without any other previous assumptions. The paper starts by analyzing amino acid sequence data by means of histograms using fixed length amino acid words (tuples). After creating the initial relative frequency histograms, they are transformed and processed in order to generate quantitative results for information extraction and graphical visualization. Selected samples from two reference datasets are used, and results reveal that the proposed method is able to generate relevant outputs in accordance with current scientific knowledge in domains like protein sequence/proteome analysis.


Fruits and vegetables belong to an essential class of foods that supply human diet with nutritive requirements including vitamins and minerals which are essential for normal body health and function. The study was carried out to determine the physico-chemical analysis and sensory qualities of mixed fruit squash. Carrot (Drocus carota), papaya (Carica papaya) and banana (Musa sapientum) juice were standardized to produce mixed squash which was stored for 9 weeks in sterilized glass bottles at room temperature. Marginal changes in pH, total soluble solids, acidity and vitamin C were observed. Estimation of vitamin C content (6.32 – 15.45 mg) of mixed squash showed high improvement in nutritional value of papaya juice incorporated with carrot and banana juice in squash. TSS (40.0 to 41.6) increased with gradual passage of storage time, which might be due to hydrolysis of polysaccharides into monosaccharide and oligosaccharides. The titratable acidity (1.25% to 2.97%) increased and pH (5.01 to 3.87) decreased progressively during the storage period might be due to the excessive fermentation and presence of lactic acid reducing micro- organism. The mean overall acceptability scores of more than 8 for mixed squash prepared up to 40% carrot juice incorporation with 40% papaya and 20% banana juice indicated the commercial scope for manufacturing good and nutritious squash from carrot, papaya and banana juice. However, the shelf life of mixed squash was established within 8 weeks. The product is recommended for children, youth and elderly persons to be used within 8 weeks.


State-of-the-art train delay prediction systems neither exploit historical data about train movements, nor exogenous data about phenomena that can affect railway operations. They rely, instead, on static rules built by experts of the railway infrastructure based on classical univariate statistics. The purpose of this paper is to build a data-driven train delay prediction system that exploits the most recent analytics tools. The train delay prediction problem has been mapped into a multivariate regression problem and the performance of kernel methods, ensemble methods and feed-forward neural networks have been compared. Firstly, it is shown that it is possible to build a reliable and robust data-driven model based only on the historical data about the train movements. Additionally, the model can be further improved by including data coming from exogenous sources, in particular the weather information provided by national weather services. Results on real world data coming from the Italian railway network show that the proposal of this paper is able to remarkably improve the current state-of-the-art train delay prediction systems. Moreover, the performed simulations show that the inclusion of weather data into the model has a significant positive impact on its performance.


Robots exhibit flexible behavior largely in proportion to their degree of knowledge about the world. Such knowledge is often meticulously hand-coded for a narrow class of tasks, limiting the scope of possible robot competencies. Thus, the primary limiting factor of robot capabilities is often not the physical attributes of the robot, but the limited time and skill of expert programmers. One way to deal with the vast number of situations and environments that robots face outside the laboratory is to provide users with simple methods for programming robots that do not require the skill of an expert. For this reason, learning from demonstration (LfD) has become a popular alternative to traditional robot programming methods, aiming to provide a natural mechanism for quickly teaching robots. By simply showing a robot how to perform a task, users can easily demonstrate new tasks as needed, without any special knowledge about the robot. Unfortunately, LfD often yields little knowledge about the world, and thus lacks robust generalization capabilities, especially for complex, multi-step tasks. We present a series of algorithms that draw from recent advances in Bayesian non-parametric statistics and control theory to automatically detect and leverage repeated structure at multiple levels of abstraction in demonstration data. The discovery of repeated structure provides critical insights into task invariants, features of importance, high-level task structure, and appropriate skills for the task. This culminates in the discovery of a finite-state representation of the task, composed of grounded skills that are flexible and reusable, providing robust generalization and transfer in complex, multi-step robotic tasks. These algorithms are tested and evaluated using a PR2 mobile manipulator, showing success on several complex real-world tasks, such as furniture assembly.


When evaluating ontogenetic shifts in isotopic composition of consumer tissues within the context of a dietary analysis, the isotopic starting point of consumers in the population should not be ignored. Neonate isotopic composition may be different from that of juveniles and adults; in general, neonate tissues are built from maternal resources rather than food resources. Thus, the range of isotope values observed within a population of consumers may be significantly impacted by consumer isotope ratios at birth. Long-term goals of my research involve the use of stable isotopes to assess the role diet plays in driving population level differences in life history and demography observed among three pigmy rattlesnake (Sistrurus miliarius; family Viperidae) populations. For meaningful interpretation of field-collected data, it was important to determine starting (i.e., at birth) isotopic compositions of rattlesnakes from the study populations. We quantified isotopic composition of pregnant pigmy rattlesnake scale tissue, isotopic composition of neonate scale tissue and the degree that neonate scale tissue isotopic composition reflected the isotopic composition of maternal scale tissue. Collectively, neonate isotopic composition was highly variable among-litters; average litter δ13C values spanned 7 ‰ and average litter δ15N values spanned 2.8 ‰. Over 95 % of the variation in offspring isotopic composition was expressed among litters. Thus, high levels of among-litter isotopic variation were largely due to the retention of a maternal signal. Results of the enclosure study suggest that highly variable isotopic signatures in young animals within field populations could easily reflect the retention of a maternal signal rather than differences in resource utilisation among younger snakes.


Abstract : Understanding the genetic basis of cancer will greatly improve our ability to develop more effective therapies. One family of genes involved in cancer is the tumor suppressor genes. We have functional evidence for a new breast cancer suppressor gene on chromosome 17. Transfer of a normal human chromosome 17 results in growth arrest of the MCF7 breast cancer cell line. We are using two approaches to localize the region containing this gene. The first involves the transfer of chromosome 17s containing specific deletions into MCF7 cells followed by our growth arrest assay to determine whether that chromosome contains the suppressor gene. We have determined that the gene lies on chromosome 17q and are now further localizing this gene. In parallel, we are studying loss of heterozygosity (or LOH, which is an indirect indicator of the presence of a suppressor gene) in breast tumors and have identified at least three candidate LOH regions on chromosome 17. Future studies will involve physical mapping of the region containing the suppressor gene, and we provide evidence for our ability to develop region-specific markers. We have also undertaken feasibility studies to determine whether YACs can be used in the MCF7 growth arrest assay.


Arginase shares a common substrate, l-arginine, with nitric oxide synthase (NOS). Both enzymes are active at inflammatory sites. To understand regulation of arginase and its relationship to nitric oxide (NO) production, we studied effects of N G-hydroxy-l-arginine (HOArg) and interleukin-4 (IL-4) on urea and[Formula: see text] synthesis by glomeruli during rat immune glomerulonephritis and compared these with macrophages and glomerular mesangial cells (MC). In nephritic glomeruli, elicited macrophages, and MC stimulated with IL-1 and adenosine 3',5'-cyclic monophosphate agonists, increased arginase and induced NOS activity was found. Urea production was inhibited by HOArg and increased by IL-4. NO inhibition [ N G-monomethyl-l-arginine (l-NMMA)] increased arginase activity in nephritic glomeruli and macrophages but not MC.[Formula: see text] synthesis was inhibited byl-NMMA and IL-4. It was increased with HOArg under conditions of NO inhibition. In contrast, in normal glomeruli and basal MC, where there was no induced NO synthesis, IL-4 had no effect on arginase activity, whereas HOArg consistently reduced it in glomeruli only. Type II arginase (Arg II) mRNA was detected in normal glomeruli; nephritic glomeruli expressed both Arg I and Arg II mRNAs. This is the first demonstration of arginase modulation in glomeruli and MC and of the expression of arginase isoforms in glomeruli. The differential responses to two endogenous compounds generated by inflammation suggest this may be part of coordinated regulation of arginase and inducible NOS in immune injury, whereby arginase is inhibited during high-output NO production and stimulated with NO suppression. This, together with control of arginase and NOS isoforms, may be important in controlling the balance of inflammatory and repair mechanisms.


Deduplication has become a widely deployed technology in cloud data centers to improve IT resources efficiency. However, traditional techniques face a great challenge in big data deduplication to strike a sensible tradeoff between the conflicting goals of scalable deduplication throughput and high duplicate elimination ratio. We propose AppDedupe, an application-aware scalable inline distributed deduplication framework in cloud environment, to meet this challenge by exploiting application awareness, data similarity and locality to optimize distributed deduplication with inter-node twotiered data routing and intra-node application-aware deduplication. It first dispenses application data at file level with an application-aware routing to keep application locality, then assigns similar application data to the same storage node at the super-chunk granularity using a handprinting-based stateful data routing scheme to maintain high global deduplication efficiency, meanwhile balances the workload across nodes. AppDedupe builds application-aware similarity indices with super-chunk handprints to speedup the intra-node deduplication process with high efficiency. Our experimental evaluation of AppDedupe against state-of-the-art, driven by real-world datasets, demonstrates that AppDedupe achieves the highest global deduplication efficiency with a higher global deduplication effectiveness than the high-overhead and poorly scalable traditional scheme, but at an overhead only slightly higher than that of the scalable but low duplicateelimination-ratio approaches.


Background Clostridium difficile infection (CDI) is a significant healthcare burden, with increased morbidity and mortality. Traditional treatment regimens using antibiotics for recurrent CDI are significantly less successful compared with 80–90% with fecal microbiota transplantation (FMT). There is a paucity of data on failure rates and mortality after FMT in CDI. This study aims to identify the rates of failure, relapse, and mortality associated with FMT as well as the risk factors for FMT failure. Methods A large retrospective cohort study was carried out including all patients who underwent FMT from December 2012 through May 2014. Patient factors (demographics, comorbidities, immune-suppression, transplant history, antibiotics used, hospitalization, and surgeries), disease factors (number of episodes of CDI, treatments, and severity), and transplant factors (route and number of FMT) were examined. Failure of treatment was defined as no resolution of diarrhea in patients who had been treated with one or more fecal microbiota transplantation within 90 days of FMT. Results A total of 201 patients (age 66.6±18.3 years, 62.2% women) were included. The overall failure rate was 12.4%. Patients with failed fecal transplant had increased number of FMTs compared with those who responded (mean 1.92±0.997 vs. 1.29±0.615; P=0.004). No colectomies or death related to CDI were found in our patient population. Significant predictors of failure were female sex (P=0.016), previous hospitalization (P=0.006), and surgery before FMT (P=0.005). The overall mortality rate was 9.0% and failure of FMT was associated with an increased risk of death (odds ratio=5.833, confidence interval 2.01–16.925; P<0.05). Conclusion FMT is a suitable alterative to antibiotic use for recurrent CDIs, with a high success rate. The results indicate that hospital-acquired CDI may be a predictor of failure of FMT.


ABSTRACT Mixtures of melt and residue in a high-T metamorphic complex have a lower density and viscosity than the surrounding host crust, and the mixtures should ascend due to buoyancy. The mixtures are recognized as migmatites in the high-T metamorphic complex. To confirm ascent of migmatites, we conducted numerical simulations of ascent of a model migmatite (buoyant viscous fluid). The numerical simulations show that the model migmatite could rise to shallow levels of a model crust so long as it is continuously produced at the bottom of the model crust. Otherwise it ceases to rise at depth due to loss of buoyancy by cooling. The numerical simulations also show that the model migmatite experiences vertical thinning during the ascent. The ascent mechanism proposed in this paper requires the continuous production of partially melted rocks at the base of the crust, which is provided by a continuous input of energy into the crust from the mantle. Given that high-T metamorphic complexes are associated with igneous activity beneath a volcanic arc, the igneous activity reflects the energy input into the lower crust from the mantle. A high-grade part (migmatites) of a high-T metamorphic complex in the Omuta district of northern Kyushu, southwest Japan, experienced thinning during ascent. Large amount of igneous rocks, such as plutonic and volcanic rocks, are also distributed in northern Kyushu. Zircon U–Pb ages of igneous rocks from northern Kyushu reveal that igneous activity continued from 115 to 93 Ma, and that peak igneous activity at 110–100 Ma was synchronous with the ascent of migmatites of the high-T metamorphic complex in northern Kyushu. Therefore, the numerical simulations may provide an appropriate model of the ascent of migmatites of the high-T metamorphic complex beneath a volcanic arc, at the eastern margin of Eurasia in the mid-Cretaceous. GRAPHICAL ABSTRACT


The relevance of foreign languages within educational systems is indisputable. They have become a key element on account of globalisation, new technologies and the arrival of the so-called Communication Era. Governments and educational centres, motivated by the pressure of the labour market and the very interest of educational agents (teachers, families, students), have been crucial to make of this field a prominent axis of educational projects. In an increasingly global and competitive society, the external evaluation of languages has been established to validate the quality of educational systems and to provide students with certificates and diplomas which grant access to different educational institutions, international mobility or the labour market itself. In particular, this Master's Dissertation analyses the DELF-DALF diplomas (Diplôme d'Études de Langue Française and Diplôme Approfondi de Langue Française). These certifications are organised by the French Ministry of Education through the CIEP (Centre International d'Études Pédagogiques) and have been adapted to the Common European Framework of Reference for Languages (CEFRL). The interest of this work is to analyse how language proficiency is evaluated and certified by external institutions within multilingual environments. We thoroughly examine the evaluation method of these diplomas regarding their evaluation rubrics, descriptors and format so as to extract some of the specific circumstances that may influence the linguistic performance of bilingual speakers. The author, teacher of French as a foreign language and corrector-examiner of DELF-DALF diplomas, performs a theoretical analysis according to the foundations of the exams, the linguistic features of bilingual speakers and the public-domain correction criteria of the DELF-DALF diplomas.


Future climate change projections are not limited to a simple warming, but changes in precipitation and sea level pressure (SLP) are also projected. The SLP changes and the associated atmospheric circulation changes could directly mitigate or enhance potential projected changes in temperature and precipitation associated with rising temperatures. With the aim of analysing the projected circulation changes and their possible impacts on temperature and precipitation over Europe in summer [June–July–August (JJA)], we apply an automatic circulation type classification method, based on daily SLP, on general circulation model (GCM) outputs from the Coupled Model Intercomparison Project phase 5 (CMIP5) database over the historical period (1951–2005) and for climate under two future scenarios (2006–2100). We focus on summer as it is the season when changes in temperature and precipitation have the highest impact on human health and agriculture. Over the historical observed reference period (1960–1999), our results show that most of the GCMs have significant biases over Europe when compared to reanalysis data sets, both for simulating the observed circulation types and their frequencies, as well as for reproducing the intraclass means of the studied variables. The future projections suggest a decrease of circulation types favouring a low centred over the British Isles for the benefit of more anticyclonic conditions. These circulation changes mitigate the projected precipitation increase over north‐western Europe in summer, but they do not significantly affect the projected temperature increase and the precipitation decrease over the Mediterranean region and eastern Europe. However, the circulation changes and the associated precipitation changes are tarnished by a high uncertainty among the GCM projections.


Food shortage has been a problem in Swaziland (now Eswatini) due to many factors not limited food base. A study on cassava production in Eswatini was conducted to determine awareness of producers and non-producers, sources of awareness of cassava cultivation and challenges faced in cassava cultivation. Systematic random sampling technique was used to select 441 respondents consisting of 195 cassava producers and 246 non-producers. A valid and reliable (r=.89) questionnaire was used to collect data. Findings of the study revealed that both cassava producers and non-producers were aware of cassava cultivation but one non-producer claimed not to be aware. The major sources of information included: other farmers, neighbours and friends, radio, Extension agents from NGOs and Government Extension Agents. Cassava producers encountered many challenges in cassava cultivation mainly: harvesting energy demand, pest infestation (cassava mosaic, mealy bug and caterpillars), non-availability of planting material, mechanization of planting, non-availability of market, burrowing animals eat tubers, and bacterial blight disease. The conclusion was that producers including nonproducers were aware of cassava production mainly through informal sources and less from Government Extension agents. It was recommended that Government Extension Agents should strengthen their educational effort to educate farmers in order to address some of the challenges and motivate them to engage in cassava production and change their attitude towards cassava cultivation.


Many countries face aging populations, and this is accompanied by discussions of how people can stayemployed later in life. This raises the question of how organizations can attract, retain, and develop olderworkers for productive working lives. This paper presents a study in Sweden of pensioners' motives forparticipating in work and learning activities. Of 232 individuals, 83 (35.8 %) had worked after retirement,but only four had worked full time. The main motives for continuing to work and learn were (1) stayingactive, (2) social contact, and (3) the content of the activity. The motive of staying active, which reflects adesire to stay healthy, might be enhanced with age and is rarely included in discussions about workmotivation. Using self-determination theory to interpret the results, a suggestion is that organizationsshould use separate strategies for organizing work and learning for younger and older workers.


Radio and memory form a radical coupling, stitching together musical cultures with personal psychologies. I pursue such relations in Phantom Music by focusing on, and unpacking a project I developed for exhibition in 2005. The project, Phantom Radio, is based on forming a library of radio memory. Collecting stories from 105 individuals from around the world, the library consists of written statements and CDs of all the songs mentioned. Through the project, questions of broadcast technology, and the work of memory, are brought forward. To pursue such questions, the following article maps out the territory explored in the project. Reflecting on various threads, from habits of listening to the effects of music on individual lives, leads to a tracing out of the 'phantasmic' and the 'social' aspects of radio. And further, how music supplies a form of shared ground to the individual instances of unexpected experiences.


Background: Combination of atracurium and vecuronium is a good alternative for rapid tracheal intubation in certain conditions where one has to avoid giving succinylcholine as a muscle relaxant. It has been shown good synergism between two drugs for mechanism of action, duration of action, haemodynamic stability, and recovery from anaesthesia. Materials and Methods: A total of 75 patients were studied in 3 groups having 25 patients in each. Intubating conditions were studied after 75 seconds and 90 seconds in combination of atracurium and vecuronium with same dose. Pulse rate and systolic blood pressures were monitored during intubation and subsequently during maintenance. Results: Combination of atracurium and vecuronium gave clinically acceptable intubating condition in majority of patients in 75 seconds but in 90 seconds, it gave similar results to that of suxamethonium at the cost of longer duration. Alone vecuronium is not a suitable non depolarizing muscle relaxant for rapid sequence induction. No significant difference in haemodynamic data were noted in all three groups. Good and early recovery was noted in combination of atracurium and vecuronium. Combination of two drugs was synergistic and more potent in an equipotent dose ratio favouring one parent drug so maximum reduction of drug requirement would be about 40%.


T his paper reports on the design, delivery and assessment of a model for internal library education around research data management (RDM). Conducted at the University of Pittsburgh Library System (ULS), the exercise and resultant instructional session employed an active learning approach, in which a group of librarians and archivists explored data issues and conventions in a discipline of their own selection and presented their findings to an audience of library colleagues. In this paper, we put forth an adaptable active learning model for internal RDM education and offer guidance for its implementation by peer libraries that are similarly building internal capacity for the design and delivery of RDM services that are responsive to disciplinary needs .


Abstract

Objective – In this case study, librarians at the William H. Hannon Library at Loyola Marymount University explored user behaviour in the Information Commons, user preferences for furniture style and configuration, and how users engaged with a mix of technology, resources, and activities inside the space.

Methods – The researchers used a mixed-methods case study consisting of 2,443 "direct observations," 646 environmental scans, 248 patron surveys, and 46 whiteboard poll questions. They created visualizations of results in Tableau, with filters for zone and variable. They then carried out a follow-up furniture preferences survey with 190 respondents.

Results – Independent study dominated the space usage. Users valued spaciousness, quiet, privacy, and a clean environment. Users frequently multi-tasked with additional devices as they simultaneously used the library computers, including cell phones, headphones, and laptops. The majority of students self-reported using a library computer for email and to access the campus online learning platform. They also reported reading/studying and printing as frequent activities, although these were less frequently observed. Unattended belongings were observed along with broken electrical outlets. Temperature and noise levels were highly variable.

Conclusions – This methodology allowed for the exploration of space use and satisfaction and uncovered implications for the redesign of the library space. The library has already taken steps toward making improvements based on this assessment project including: removing some reference stacks in favor of additional seating space, an inventory of all electrical outlets, and the exploration of new furniture and noise control strategies.


Physical therapists often use casting as an adjunct to traditional management of patients with brain injury. Casts generally are used on these patients for one of two reasons: 1) to increase range of motion with the use of serial casting or 2) to augment functional treatment with the use of inhibitive casting. This clinical report describes serial and inhibitive casts and introduces a precasting work sheet that promotes the selection of appropriate casting patients and necessary planning. The work sheet guides the therapist through an assessment of patient data relevant to casting, including passive range of motion, postural tone and abnormal reflexes, and voluntary movement. The precasting work sheet helps therapists gain expertise in casting by familiarizing them with the factors to consider before casting, encouraging them to set goals for casting, and helping them to determine whether the goals were met.


Upper tracheal obstruction, stridor and dispnea developed in a 53 year-old woman because of a large calcified benign goiter. There was a mass of 3 to 4 cm in size with calcification located on the right side of trachea and in the substernal region on the chest roentgenography. CT revealed bilaterally nodular substernal goiter and tracheal compression with the calcified nodule. Cytological finding of fine needle aspiration biopsy was benign goiter. Bilateral subtotal thyroidectomy was performed to the patient with the diagnosis of substernal benign goiter without any complication. [Journal of Turgut Ozal Medical Center 1996;3(3):203-205]


Antiferroelectric liquid crystals are considered as smarter materials for display technologies owing to their faster response time over conventional nematics. However there is large scope for modifications of its physical properties. In the present study multiwalled carbon nanotubes (MWCNT) are dispersed in a high tilted antiferroelectric liquid crystal composed of rod like molecules. The effects of nano-dispersion on electro-optical and dielectric properties of the host are studied in details. The time for switching between dark and bright states and the rotational viscosity are reduced and spontaneous polarization is enhanced considerably by minute addition of MWCNTs. The high tilt angle of the molecules necessary for obtaining good dark state in displays has not changed after dispersion of nanotubes. The strong interaction of the aromatic cores of the rod like liquid crystal molecules with the honey-comb pattern of the CNT walls is considered responsible behind such improvements of physical properties of the host. Copyright © 2016 VBRI Press.


This study shows that a limiting dispersed phase particle size exists at very low concentrations for polymer blends mixed in an internal batch mixer and two types of twin-screw extruders. The Taylor limit for breakup of a single drop in a matrix underpredicts the limiting particle size; this discrepancy is attributed to viscoelastic effects. For uncompatibilized blends, the final particle size increases with the dispersed phase concentration due to increased coalescence. The particle size distribution also broadens at higher concentrations. Using in-situ reaction during blending or adding premade diblock copolymers suppresses coalescence resulting in smaller particle size and narrower particle size distribution. Using premade block copolymers is not as efficient in stabilizing morphology as using reactive polymers. It is shown that the main advantage of using compatibilizers in polymer blends is the suppression of coalescence achieved through stabilizing the interface, not a reduction in the interfacial tension. There is a critical shear rate in polymer systems where a minimum particle size is achieved. A qualitative explanation of why this occurs is given based on droplet elasticity


Despite the strong increase in the modal share of cycling in several European cities, cycling under the influence of alcohol and drugs (CUI) does not seem to have attracted enough attention from researchers and authorities, while recent scientific studies are almost non-existent. The present study addresses this gap of knowledge by providing an overview of current situation regarding legislation, enforcement and preventive measures on CUI based on a questionnaire survey on 15 IRTAD member countries. It is evident that CUI is an emerging problem, growing in parallel with cycling itself, not properly addressed since enforcement and provision for measures to prevent it are insufficient: in over one third of the examined countries, there is no penalty for CUI. The overview and discussion on CUI practices is expected to assist in the identification and prioritization of CUI needs.


The cDNA clone encoding the fast-twitch isoform of myosin light chain 1 (MLC-1f) was isolated from bovine longissimus dorsi muscle and sequenced in M13 and pUC8. An 0.8-kb subclone, produced by digestion of the cDNA with EcoRI, contained the portion of the molecule common to MLC-1f and MLC-3f. The cDNA in pUC8 contained an additional 81 bp upstream of the EcoR I digestion site, which was unique to MLC-1f. The cDNA clone was used to measure MLC-1f mRNA in longissimus dorsi muscle of cattle chronically administered the beta-adrenergic agonist clenbuterol. Treatment with clenbuterol for 50 days increased succinic dehydrogenase negative (type IIB) and positive (types I and IIA) myofiber cross-sectional areas by 25%. After the 50-day treatment period, the amount of MLC-1f mRNA was 90% greater in longissimus dorsi muscle of treated animals than in the initial group. This effect was lost when clenbuterol treatment was withdrawn for a 78-day period, during which time muscle growth in the treated animals stopped completely. We conclude that we have cloned the bovine cDNA for MLC-1f, which has provided additional evidence that beta-adrenergic agonists increase myofibrillar gene expression.


Male patients over 50 years with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) are potential candidates for prostatic artery embolization (PAE). PAE is not a perfect fi t for all BPH patients. Careful pre- and postpostprocedural evaluation/consultation with correct selection of patients should be tailored on an individual basis. Evaluated parameters include the following: LUTS severity quanti fi cation with validated questionnaires as the international prostate symptom score (IPSS) and qualityof life(QoL),erectileandejaculatoryevaluationwithvalidatedquestionnaires,blood tests including full blood count, coagulation pro fi le, renal function and total/free prostate-speci fi c antigen (PSA), prostate volume measured by multiparametric magnetic resonance (mpMR) of the prostate and/or transrectal ultrasound, uro fl owmetry measuring the peak urinary fl owrate (Qmax), and postvoid residual urine (PVR). Correct arterial anatomy identi fi cation with either computed tomography (CT) angiography, MR angiography, or intraprocedural cone-beam CT (CBCT) are suggested for a con fi dent procedure and avoiding potential complications. The minimally invasive nature of PAE with a faster recovery, preserving the sexual function, and comparable results to standard prostatic surgery make the procedure an attractive choice for many male patients suffering with this condition.Patientsshouldbeinformedabout thepotentialforhigherretreatmentratesand shorter duration of treatment effect when compared with standard prostatic surgery. In this comprehensive review, we provide an updated toolbox for all interventional radiologists interested in the PAE practice for patients with BPH. We explain how to evaluate patients during consultation before and after PAE, describe the preprocedural imaging required, explain the technique, and narrate how to optimize outcomes. Finally, we review the level of evidence of PAE for BPH.


This study examines the role of nitrogen transformations in the acidification of soil under stock urine patches, specifically the formation of acidic subsurface layers. These are horizontal planes of acidity several centimetres below the soil surface. Glasshouse studies were conducted to relate nitrogen transformations to measured pH changes in soil treated with urine or urea solution (simulated urine). Acidic subsurface layers formed in both urine- and simulated urine-treated soil. With the development of a H + balance model, the contribution of nitrogen transformations to changes in the H + concentrations in simulated urine patches was determined. During the first 9 days following treatment, urea hydrolysis and NH3 volatilisation dominated changes in H + concentration. After that, net immobilisation contributed to H + changes; however, nitrification was the dominant process occurring. Downward movement of NH4 + originating from urea hydrolysis allowed more nitrification to occur in lower soil layers. The net result of these processes was net acidification of the 4-6, 6-8, and 8-10 cm layers by approximately 0.7, 0.6, and 0.3 pH units, respectively. Thus nitrogen transformations were responsible for the formation of acidic subsurface layers in simulated stock urine patches within 6 weeks of application. SR03 J R. et al Aci ace st tc Additional keywords: acidification, soil pH, urea, nitrification, H + budget.


Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as 'is genotoxic,' 'is immunosuppressive' or 'modulates receptor-mediated effects,' and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.


In 2011, the U.S. reported 3 million child maltreatment cases, an uncomfortably high but recurring figure each year. Research shows exposure to early life stress (ELS) increases an individual's susceptibility to substance abuse, specifically of nicotine, alcohol, and cocaine. Increased susceptibility may result from dysregulation of the HPA axis sustaining activation into adulthood after ELS. Hyperactivation of the HPA axis significantly reduces hippocampal BDNF, a neurotrophin involved in neuronal growth and plasticity. Reduced hippocampal BDNF may be a factor in substance abuse vulnerability. Additionally, research shows exercise protects hippocampal BDNF from stress induced down-regulation. To explore these relationships, this study used maternal separation (MS) to model ELS in rats. Following MS, rats voluntarily exercised for three weeks, or were sedentary, followed by cocaine conditioned place preference. We quantified hippocampal BDNF from these groups and predicted MS would down-regulate BDNF and exercise would ameliorate this effect. Finally, we predicted BDNF levels would correlate with total running activity. We found no significant effect of MS or exercise, and total running activity weakly correlated with BDNF expression. Our results parallel the behavioral results of this experiment, in which there also were no significant effects of exercise on sensitivity to the locomotor or rewarding effects of cocaine. Thus, although no significance was found in this study, it may provide further insight into the relationships between ELS, exercise, and substance abuse and provide footing for improvement in the development of designs exploring them.