INTRODUCTION AND OBJECTIVES: A recent study demonstrated that a validated model was more accurate in predicting de novo stress urinary incontinence (SUI) than both preoperative stress testing and expert prediction. However, this model was validated using a population that was 85% White. The study objective was to evaluate if this model correctly predicted de novo SUI after pelvic organ prolapse (POP) surgery in a diverse population. METHODS: This is a retrospective review of women without SUI who underwent POP surgery with or without a prophylactic incontinence procedure from January 2014 to January 2017. Charts were reviewed for demographic/clinical information and patient report of SUI up to 12 months after surgery. Patient characteristics were entered into the risk calculator and predicted risk was compared to actual outcome. RESULTS: 95 women without SUI underwent POP surgery during the inclusion period. 39 (48.2%) were Hispanic, 18 (22.2%) Black, 13 (16.1%) White, and 11 (13.6%) Other. 14 women developed de novo SUI (14.7%). Women with de novo SUI had a significantly higher BMI, smoking rate, and POPQ Aa point. The overwhelming majority of patients who developed de novo SUI were of Hispanic background (85.7%) There was no difference in the mean predicted percentage risk of de novo SUI after POP surgery without a concomitant incontinence procedure in women who developed SUI (36.2 95%CI 31.2-41.3) versus women who did not develop SUI postoperatively (33.0 95%CI 31.4-34.6). The majority of patients (85.7%) developed SUI within 6 months after surgery. Only 12 women underwent a prophylactic incontinence surgery at time of POP repair, of whom one patient developed de novo SUI, precluding comparison of these two groups. CONCLUSIONS: A risk calculator predicting de novo SUI after POP surgery without an incontinence procedure validated using a primarily White population did not correctly predict de novo SUI in this diverse population. The racial/ethnic composition of data sets used to create predictive models may affect its application in certain patient populations. Additional studies in diverse populations are needed to confirm these findings. Figure. No caption available. Source of Funding: None


Emerging technologies are fueling a third paradigm of education. Digital, networked and mobile media are enabling a disruptive transformation of the teaching and learning process. This paradigm challenges traditional assumptions that have long characterized educational institutions and processes, including basic notions of space, time, content, and learning outcomes. Innovative educators have an opportunity to blend face-to-face and digital learning models to advance an engaged, effective, efficient and affordable model of learning in the 21st century. This emerging paradigm includes changes in at least five key teaching and learning dimensions, including the direction of communication, the level of interactivity, the media of communication, the constraints on the educational process, and the learning outcomes. Recommendations for implementing new teaching and learning techniques are offered.


We develop parametric inference procedures for large panels of noisy option data in a setting, where the underlying process is of pure-jump type, i.e., evolves only through a sequence of jumps. The panel consists of options written on the underlying asset with a (different) set of strikes and maturities available across the observation times. We consider an asymptotic setting in which the cross-sectional dimension of the panel increases to infinity, while the time span remains fixed. The information set is augmented with high-frequency data on the underlying asset. Given a parametric specification for the risk-neutral asset return dynamics, the option prices are nonlinear functions of a time-invariant parameter vector and a time-varying latent state vector (or factors). Furthermore, no-arbitrage restrictions impose a direct link between some of the quantities that may be identified from the return and option data. These include the so-called jump activity index as well as the time-varying jump intensity. We propose penalized least squares estimation in which we minimize the L2 distance between observed and model-implied options. In addition, we penalize for the deviation of the model-implied quantities from their model-free counterparts, obtained from the high-frequency returns. We derive the joint asymptotic distribution of the parameters, factor realizations and high-frequency measures, which is mixed Gaussian. The different components of the parameter and state vector exhibit different rates of convergence, depending on the relative (asymptotic) informativeness of the high-frequency return data and the option panel.


Peatlands represent an enormous carbon reservoir and have a potential impact on the global climate because of the active methanogenesis and methanotrophy in these soils. Uncultivated methanotrophs from seven European peatlands were studied using a combination of molecular methods. Screening for methanotroph diversity using a particulate methane monooxygenase-based diagnostic gene array revealed that Methylocystis-related species were dominant in six of the seven peatlands studied. The abundance and methane oxidation activity of Methylocystis spp. were further confirmed by DNA stable-isotope probing analysis of a sample taken from the Moor House peatland (England). After ultracentrifugation, (13)C-labelled DNA, containing genomic DNA of these Methylocystis spp., was separated from (12)C DNA and subjected to multiple displacement amplification (MDA) to generate sufficient DNA for the preparation of a fosmid metagenomic library. Potential bias of MDA was detected by fingerprint analysis of 16S rRNA using denaturing gradient gel electrophoresis for low-template amplification (0.01 ng template). Sufficient template (1-5 ng) was used in MDA to circumvent this bias and chimeric artefacts were minimized by using an enzymatic treatment of MDA-generated DNA with S1 nuclease and DNA polymerase I. Screening of the metagenomic library revealed one fosmid containing methanol dehydrogenase and two fosmids containing 16S rRNA genes from these Methylocystis-related species as well as one fosmid containing a 16S rRNA gene related to that of Methylocella/Methylocapsa. Sequencing of the 14 kb methanol dehydrogenase-containing fosmid allowed the assembly of a gene cluster encoding polypeptides involved in bacterial methanol utilization (mxaFJGIRSAC). This combination of DNA stable-isotope probing, MDA and metagenomics provided access to genomic information of a relatively large DNA fragment of these thus far uncultivated, predominant and active methanotrophs in peatland soil.


When participants in psychophysical experiments are asked to estimate or identify stimuli which differ on a single physical dimension, their judgments are influenced by the local experimental context — the item presented and judgment made on the previous trial. It has been suggested that similar sequential effects occur in more naturalistic, real-world judgments. In three experiments we asked participants to judge the prices of a sequence of items. In Experiment 1, judgments were biased towards the previous response (assimilation) but away from the true value of the previous item (contrast), a pattern which matches that found in psychophysical research. In Experiments 2A and 2B, we manipulated the provision of feedback and the expertise of the participants, and found that feedback reduced the effect of the previous judgment and shifted the effect of the previous item's true price from contrast to assimilation. Finally, in all three experiments we found that judgments were biased towards the centre of the range, a phenomenon known as the "regression effect" in psychophysics. These results suggest that the most recently-presented item is a point of reference for the current judgment. The findings inform our understanding of the judgment process, constrain the explanations for local context effects put forward by psychophysicists, and carry practical importance for real-world situations in which contextual bias may degrade the accuracy of judgments.


There is increased pressure and incentive for Primary Care Trusts to ask general practitioners to prescribe generic statins and switch patients from branded statins. Whilst this seems attractive in an increasingly cost-aware NHS, there are many issues and implications involved in switching statins that are not always fully considered. With statins playing such a vital role in reducing mortality and morbidity in cardiovascular disease, switching to a cheaper statin can seem a good option. However, cost does not always reflect cost-effectiveness. A round table meeting was recently convened by The British Journal of Cardiology to discuss these issues. The expert panel considered the differences between statins and their safety and efficacy, which patients are suitable for switching, the follow-up needed, the costs to the practice in making a switch, and how patients can be involved in this process and their concordance optimised. The panel looked at the implications of switching patients in relation to both current and anticipated future guidelines for cholesterol targets and the Quality and Outcomes Framework, and at organisational changes taking place in general practice in relation to prescribing. This supplement is a summary of the presentations made during the meeting and the lively round table discussion. We hope it will help primary care teams weigh up the evidence and think carefully about all the considerations around this issue.


In the last decade, a number of states have expanded the jurisdiction of their juvenile courts by increasing the maximum age to 18. Proponents argue that these expansions reduce crime by increasing access to the beneficial features of the juvenile justice system. Critics counter that the expansions risk increasing crime by reducing deterrence. In 2010, Illinois raised the maximum age for juvenile court for offenders who commit a misdemeanor. By examining the effect of this law on juvenile offenders in Chicago, this paper provides the first empirical estimates of the consequences of recent legislative activity to raise the age of criminal majority. Applying a difference-in-differences design with multiple control groups, we find little evidence of an effect. Our results suggest that—contrary to the expectations of both advocates and opponents—increasing the maximum age for juvenile court does not affect juvenile recidivism.


Purpose: Inflammation occurs routinely when managing gliomas and is not easily distinguishable from tumor regrowth by current MRI methods. The lack of noninvasive technologies that monitor inflammation prevents us to understand whether it is beneficial or detrimental for the patient, and current therapies do not take this host response in consideration. We aim to establish whether a gadolinium (Gd)-based agent targeting the inflammatory enzyme myeloperoxidase (MPO) can selectively detect intra- and peritumoral inflammation as well as glioma response to treatment by MRI. Methods: We carried out serial Gd-bis-5-HT-DTPA (MPO-Gd) MRI before and after treating rodent gliomas with different doses of oncolytic virus (OV) and analyzed animal survival. The imaging results were compared with histopathologic and molecular analyses of the tumors for macrophage/microglia infiltration, virus persistence, and MPO levels. Results: Elevated MPO activity was observed by MRI inside the tumor and in the peritumoral cerebrum at day 1 post–OV injection, which corresponded with activation/infiltration of myeloid cells inhibiting OV intratumoral persistence. MPO activity decreased, whereas tumor size increased, as the virus and the immune cells were cleared (days 1–7 post–OV injection). A 10-fold increase in viral dose temporally decreased tumor size, but augmented MPO activity, thus preventing extension of viral intratumoral persistence. Conclusions: MPO-Gd MRI can distinguish enhancement patterns that reflect treatment-induced spatiotemporal changes of intratumoral and intracerebral inflammation from those indicating tumor and peritumoral edema. This technology improves the posttreatment diagnosis of gliomas and will increase our understanding of the role of inflammation in cancer therapy. Clin Cancer Res; 17(13); 4484–93. ©2011 AACR.


The protection of marine megafauna within Europe is rather fragmented. Developing conservation measures for highly mobile species presents definite challenges, particularly due to the many knowledge gaps. Recent studies have shown that these gaps can be filled in by Platforms of Opportunity (PO) which create low-cost approaches. However, the number of wildlife tour operators actively collecting PO data related to distribution and relative abundance of marine fauna remains limited. In this study, we investigated whether effort-corrected data on marine megafauna facilitated by a wildlife tour operator afforded robust long temporal data (2011-2015). Sightings data, collected in the wider Mount's Bay area (southwest Cornwall, UK), along with a GPS application, were collected to accurately record survey effort. In addition, radial sighting distances and detection curves were computed to explore the robustness of the data. Density maps of marine megafauna indicated that encounters occurred throughout the area in all three seasons but the temporal distribution was significantly different with numbers peaking in autumn. Odontocetes were mostly recorded during autumn, basking shark (Cetorhinus maximus) and ocean sunfish (Mola mola) were more abundant during summer and leatherback turtles (Dermochelys coriacea) were recorded occasionally. Our data showed that this shallow coastal environment is particularly important as a nursing area for harbour porpoises (Phocoena phocoena). Risso's dolphins (Grampus griseus) showed a high semi-residency pattern for adults with calves within one core-habitat. As such, the study provides important spatial and temporal baseline data that are essential for the protection of marine megafauna through the development of an ecological network of marine protected areas within UK waters. Although, data facilitated by wildlife operators have certain shortcomings we highlight that the protocols developed here secured efficient and precise data. Such collection protocols can be implemented on a larger scale, ultimately enhancing research monitoring efforts and marine ecosystem management.


CHILDREN IN EARLY CARE AND EDUCATION PROGRAMS All families with children need child care at one time or another, and increasingly, parents seek child care so they can work outside of the home. During the past two decades, the proportion of mothers of young children entering the labor force nearly doubled, reaching 68% in 1992, with a concomitant dramatic increase in the number of children younger than 5 years who receive some form of out-of-home child care. Currently, about 80% of children entering school have had regular care in either child care centers (nonresidential settings that provide care and education for any number of children), nursery schools or preschools, their own homes, the homes of relatives, or, most frequently, family day cane homes (the homes of the care givers in which care and education are provided for either a small [1 to 6] or large [7 to 12] number of children). The types of child care arrangements and the extent to which they are used vary according to the child9s age and the income, education, and employment status of the parents. Older preschool children, children whose mothers have more than high school educations, and children whose families9 incomes are higher are more likely to be enrolled in center-based care. Unemployed parents also tend to use care in centers rather than cane in the child9s or another family9s home, presumably because subsidized center-based child care programs are available for them. Overall, however, poor families are less likely to make use of preschool programs for their 3- to 4-year-old children than are more affluent families.


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This Commentary examines the link between monetary policy and income and wealth inequality by reviewing the theoretical channels that have been proposed and examining the empirical evidence on their importance. The analysis suggests that the magnitude of any redistributive consequences of conventional monetary policy seems to be small. Evidence that unconventional monetary policies have led to increases in inequality is still inconclusive.


Recently, the World Health Organization approved the nifurtimox–eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ∼1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.


The human figure made a spectacular return in visual art and literature in the 1920s. Following modernism's withdrawal, nonobjective painting gave way to realistic depictions of the body and experimental literary techniques were abandoned for novels with powerfully individuated characters. But the celebrated return of the human in the interwar years was not as straightforward as it may seem. In Realism after Modernism, Devin Fore challenges the widely accepted view that this period represented a return to traditional realist representation and its humanist postulates. Interwar realism, he argues, did not reinstate its nineteenth-century predecessor but invoked realism as a strategy of mimicry that anticipates postmodernist pastiche. Through close readings of a series of works by German artists and writers of the period, Fore investigates five artistic devices that were central to interwar realism. He analyzes Bauhaus polymath Laszlo Moholy-Nagy's use of linear perspective; three industrial novels riven by the conflict between the temporality of capital and that of labor; Brecht's socialist realist plays, which explore new dramaturgical principles for depicting a collective subject; a memoir by Carl Einstein that oscillates between recollection and self-erasure; and the idiom of physiognomy in the photomontages of John Heartfield. Fore's readings reveal that each of these "rehumanized" works in fact calls into question the very categories of the human upon which realist figuration is based. Paradoxically, even as the human seemed to make a triumphal return in the culture of the interwar period, the definition of the human and the integrity of the body were becoming more tenuous than ever before. Interwar realism did not hearken back to earlier artistic modes but posited new and unfamiliar syntaxes of aesthetic encounter, revealing the emergence of a human subject quite unlike anything that had come before.


Contemporary Indian English: Variation and Change offers the first comprehensive description of Indian English and its emerging regional standard in a corpus-linguistic framework. Drawing on a wealth of authentic spoken and written data from India (including the Kolhapur Corpus and the International Corpus of English), this book explores the dynamics of variation and change in the vocabulary and grammar of contemporary Indian English. The aims are to document the extent of lexical and grammatical nativization at the beginning of the twenty-first century and compare contemporary Indian English to other varieties around the world (for example British and American English). The results are relevant to sociolinguists, variationists and lexicologists seeking to investigate ongoing language change in emerging standard varieties of English. With its strong empirical foundation and its comparative outlook, the book is also of interest to anyone looking for an introduction to the corpus-based description of varieties of English.


In this paper we give a generalization of the serial costsharing rule de…ned by Moulin and Shenker (1992) for cost sharing problems. According to the serial cost sharing rule, agents with low demands of a good pay cost increments associated with low quantities in the production process of that good. This fact might not always be desirable for those agents, since those cost increments might be higher than others, for example with concave cost functions. In this paper we give a family of cost sharing rules which allocates cost increments in all the possible places in the production process. And we characterize axiomatically each of them by means of an axiomatic characterization related to the one given for the serial cost-sharing rule by Moulin and Shenker (1994). JEL classi…cation: C71


In 2002-2004, a study was carried out, based on a field experiment set up on soil of very good rye complex. The experiment was designed as randomized sub-blocks with three replications. Two methods of soil tillage, conventional and simplified tillage, and seven weeding methods such as application of the following herbicides 1) control object – without herbicides, 2) Plateen 41,5 WG , 3) Plateen 41,5 WG + Fusilade Forte 150 EC, 4) Plateen 41,5 WG + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC, 5) Barox 460 SL, 6) Barox 460 SL + Fusilade Forte 150 EC, 7) Barox 460 SL + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC), constituted experimental factors. Phosphorus content in the tubers of cultivar Wiking potato was determined by colorimetry and calcium was tested by the atomic absorption spectrophotometry method (AAS). Phosphorus and calcium content and their uptake with tubers yield significantly depended on the tillage methods and weed control methods as well as weather conditions in the study years. Potato tubers from the simplified tillage cultivation had more phosphorus than tubers whose cultivation was based on the conventional tillage, in contrast to calcium, which was more abundant in tubers from the conventional method. The herbicides significantly reduced the phosphorus content and increased the calcium content compared with the control object. Phosphorus and calcium uptake by potato was significantly higher in the conventionally tilled treatments compared with the simplified method, and in the herbicide-treated plots compared with the mechanically cultivated control treatment.


Propofol is an anesthetic agent suspended in an emulsion system that includes egg yolk lecithin and soybean oil, because of which, there is concern about the use of propofol in patients allergic to these substances. We examined the association between propofol administration and incidence of adverse events in dogs with allergy to egg yolk lecithin and soybean oil. On the basis of the findings of an allergen-specific immunoglobulin E (IgE) test, 14 dogs with high levels (high-IgE group) and 7 dogs with low levels (normal-IgE group) of IgE were selected. Following intravenous administration of propofol, the incidence of anaphylactic reactions and plasma histamine concentrations under general anesthesia maintained with isoflurane throughout surgery were compared between the two groups. The frequency of anaphylactic reactions and plasma histamine concentrations were compared by the chi-square test and Student t-test, respectively. The statistical significance for both tests was set at P<0.05. In the high- and normal-IgE groups, the average frequencies of anaphylactic reactions after propofol administration were 21.4 and 14.3%, and the mean plasma histamine concentrations were 167.9 ± 94.5 nM and 65.7 ± 40.3 nM, respectively. Animals of neither groups experienced shock-like symptoms. These results revealed that propofol might be relatively safe, although careful perioperative anesthesia monitoring and standby protocols are required when using propofol in dogs with a history of allergic diseases or high chicken- or soybean-specific IgE levels.


Abstract. In this study the properties of polar mesospheric clouds (PMCs) and the background atmosphere in which they exist are studied using measurements from two instruments, OSIRIS and SMR, on board the Odin satellite. The data comes from a set of tomographic measurements conducted by the satellite during 2010 and 2011. The expected ice mass density and cloud frequency for conditions of thermodynamic equilibrium, calculated using the temperature and water vapour as measured by SMR, are compared to the ice mass density and cloud frequency as measured by OSIRIS. We find that assuming thermodynamic equilibrium reproduces the seasonal, latitudinal and vertical variations in ice mass density and cloud frequency, but with a high bias of a factor of 2 in ice mass density. To investigate this bias, we use a simple ice particle growth model to estimate the time it would take for the observed clouds to sublimate completely and the time it takes for these clouds to reform. We find a difference in the median sublimation time (1.8 h) and the reformation time (3.2 h) at peak cloud altitudes (82–84 km). This difference implies that temperature variations on these timescales have a tendency to reduce the ice content of the clouds, possibly explaining the high bias of the equilibrium model. Finally, we detect and are, for the first time, able to positively identify cloud features with horizontal scales of 100 to 300 km extending far below the region of supersaturation ( > 2 km). Using the growth model, we conclude these features cannot be explained by sedimentation alone and suggest that these events may be an indication of strong vertical transport.


"The first full-length study of the Old English version of Bede's masterwork, dealing with one of the most important texts to survive from Anglo-Saxon England. The subjects treated range from a detailed analysis of the manuscripts and the medieval use of them to a very satisfying conclusion that summarizes all the major issues related to the work, giving a compelling summary of the value and importance of this independent creation. Dr Rowley convincingly argues that the Old English version is not an inferior imitation of Bede's work, but represents an intelligent reworking of the text for a later generation. An exhaustive study and a major scholarly contribution." GEORGE HARDIN BROWN, Professor of English emeritus, Stanford University. The Old English version of Bede's Historia ecclesiastica gentis anglorum is one of the earliest and most substantial surviving works of Old English prose. Translated anonymously around the end of the ninth or beginning of the tenth century, the text, which is substantially shorter than Bede's original, was well known and actively used in medieval England, and was highly influential. However, despite its importance, it has been little studied. In this first book on the subject, the author places the work in its manuscript context, arguing that the text was an independent, ecclesiastical translation, thoughtfully revised for its new audience. Rather than looking back on the age of Bede from the perspective of a king centralizing power and building a community by recalling a glorious English past, the Old English version of Bede's Historia transforms its source to focus on local history, key Anglo-Saxon saints, and their miracles. The author argues that its reading reflects an ecclesiastical setting more than a political one, with uses more hagiographical than royal; and that rather than being used as a class-book or crib, it functioned as a resource for vernacular preaching, as a corpus of vernacular saints' lives, for oral performance, and episcopal authority. Sharon M. Rowley is Associate Professor of English at Christopher Newport University.


Abstract Brachiopods were one of the most diverse groups of reef-dwellers during the Paleozoic, and their degree of specialization for reef habitats provides an important way of assessing the ecologic complexity in reef communities. Silurian (Wenlockian) reef brachiopods in Gotland and Wisconsin are compared to level-bottom brachiopods in Gotland, Wisconsin, and the Welsh Borderland. The reef—level-bottom comparisons are made at the level of single bulk samples, as combined groups of samples from single reefs and from single level-bottom communities, and as combined groups of samples from several reefs that occupy the same stratigraphic horizon. Species diversity of reef brachiopods is higher than that of level-bottom brachiopods, but the amount of this difference decreases from the scale of entire reefs to the scale of single samples, where Shannon indices (H′) and rarefaction curves of reef and level-bottom samples commonly overlap. In terms of species richness, maximum reef values reach 44 species (n = 3452 individuals), while maximum level-bottom values reach 32 species (n = 7732 individuals). Cluster analysis separates associations of reef and level-bottom brachiopods, but there is also some compositional overlap of reef and level-bottom samples. Although the reefs contain more pedunculate brachiopods and fewer strophic, free-lying brachiopods than level bottoms, the reef brachiopods include no morphotypes or genera that are not also known from the level bottom. Wenlockian reef brachiopods in Gotland and Wisconsin were open surface dwellers with very close taxonomic, functional, and ecologic ties to level-bottom communities. As such, they indicate very similar levels of ecologic complexity between reef and high-diversity level-bottom communities. Cryptic reef brachiopods are known from the Silurian, but appear to have been rare. Brachiopods did not include common reef specialists until the Late Paleozoic. The slow pace of brachiopod specialization for reefs and the very close resemblance of Silurian reef and level-bottom brachiopods reflect the ecologic simplicity and long-term diversity plateau of the Paleozoic evolutionary fauna.


This article explores the New Zealand Government's response to the COVID-19 coronavirus pandemic through a legal and constitutional lens. It adopts an essentially doctrinal analysis in describing the response but intertwines a comparative law thread, to draw selected comparisons with how other governments have responded. It offers some political, demographical and historical insights to provide background information for non-New Zealand readers. The article aims to provide a comprehensive view of New Zealand's constitutional arrangements and how they have impacted on the Government's response to COVID-19 as well as a critical analysis of that response by assessing the effectiveness of various measures adopted by the New Zealand Government. The article consists of six sections. Section one provides an introduction to New Zealand's constitutional framework including some demographic information for non-New Zealand readers. Section two describes the New Zealand Government's overall response to the COVID-19 pandemic. Section three discusses the declaration of a national state of emergency. Section four examines the Parliamentary oversight mechanism known as the "Epidemic Response Committee". Section five explores the role of the media and the importance of upholding the right to freedom of expression when responding to the pandemic. Finally, section six draws out some overall recommendations for New Zealand and other countries to consider when moving forward and preparing for the next pandemic.


The paper develops a consumption based equilibrium model, focusing on the risk premium and the risk-free interest rate. We derive testable expressions for these quantities, and confront these with sample estimates for the 20. century. Our framework is a dynamic model in continuous time, allowing for random jumps at random time points, in addition to diffusion uncertainty. Preferences are time separable and additive. The classical equity premium puzzle and the risk-free rate puzzle are re-examined. We present values for the parameters of the representative agent's utility function for different values of risk premia and interest rates, calibrated to two first moments of the US-data of the last century. Relatively low values for agents' risk aversion are consistent with the model, but positive values of the subjective interest rate seem harder to fit.


MFIs are a major source of finance to SMEs in Kenya; it is with this in mind that Trade Development Joint Loans Board was identified for study in order to assess the various contributions it has made on SMEs in Malindi. Many sources of literature were used by the researcher to gain an in-depth knowledge and fully appreciate the contributions MFIs have made to alleviate SMEs problems all over the world, Kenya and Malindi in particular. Various research methods were used in identifying the research area, target population, and sample to study. Stratified random sampling technique was used to identify the sample for study from the target population. Descriptive statistical methods were used to analyze the data collected. Presentation of the research findings was done through tables, figures and percentages for ease of clarification and understanding. The results from the study found out that credit acquisition from TDJLB which is an MFI enhances growth of SMEs. This was reflected in 73.33% of the loanees recording various levels of increase in sales volume after loan acquisition from TDJLB. The results recorded a positive effect recorded by loanees after accessing loan facility from the board as 71.43% of the loanees used the loan to increase stock in their businesses. Among loanees interviewed, 83.33% reported that the loans issued from the board proved useful in the growth of their businesses. It was found that most loanees are married and have dependants who depend on them. The businesses they operate supplements the provision of dependants needs and wants without which, life would be difficult. Most loanees have been able to offer employment opportunities to many unemployed members of the society. Therefore, due to credit facility offered by TDJLB, many loanees have contributed to easing of unemployment crisis in the country, thereby fulfilling the objective for which the board was set. Various recommendations were forthcoming from the interviewed loanees where most suggested that, due to changed economic scenario, the maximum amount being offered my TDJLB to SMEs should be increased to more than Kenya shillings one hundred thousand, which is the present maximum amount issued by the board. Areas for further research were identified which, this study could not cover; they included a need to conduct research on why TDJLB loanees default on loans borrowed from the board. There is also a need to conduct research on the training needs of officers charged with the responsibility of managing TDJLBs. The research therefore successfully assessed the impact which Trade Development Joint Loans Board which is an MR, has had on traders in Malindi District.


We present a general Bayesian approach to probabilistic matrix factorization subject to linear constraints. The approach is based on a Gaussian observation model and Gaussian priors with bilinear equality and inequality constraints. We present an efficient Markov chain Monte Carlo inference procedure based on Gibbs sampling. Special cases of the proposed model are Bayesian formulations of non-negative matrix factorization and factor analysis. The method is evaluated on a blind source separation problem. We demonstrate that our algorithm can be used to extract meaningful and interpretable features that are remarkably different from features extracted using existing related matrix factorization techniques.


While nursing homes were insulated from civil-rights enforcement at the time of the implementation of the Medicare program and lagged behind other parts of the health sector in providing comparable access to minorities, they are the only providers for which current reporting requirements make it possible to fully assess racial disparities in use and quality of care. We find that African Americans' use of nursing homes in 2000 in the United States was 14 percent higher than Caucasians' use. The largest relative African American use of nursing homes in 2000 took place in the South and West. Average nursing-home case-mix acuity for African Americans and Caucasians were essentially identical, suggesting that shifts in payment incentives have eliminated the selective admission of easy-care private-pay (predominantly Caucasian) patients and helped fuel the growth of private pay home care and assisted living for this segment of the population. While these shifts in incentives helped increase the use of nursing homes by African Americans, a high degree of segregation and disparity in the quality of the nursing homes used by African Americans persists. Parity in use is an illusive benchmark for measuring progress in assuring equity in treatment.


In Film Blackness Michael Boyce Gillespie shifts the ways we think about black film, treating it not as a category, a genre, or strictly a representation of the black experience but as a visual negotiation between film as art and the discursivity of race. Gillespie challenges expectations that black film can or should represent the reality of black life or provide answers to social problems. Instead, he frames black film alongside literature, music, art, photography, and new media, treating it as an interdisciplinary form that enacts black visual and expressive culture. Gillespie discusses the racial grotesque in Ralph Bakshi's Coonskin (1975), black performativity in Wendell B. Harris Jr.'s Chameleon Street (1989), blackness and noir in Bill Duke's Deep Cover (1992), and how place and desire impact blackness in Barry Jenkins's Medicine for Melancholy (2008). Considering how each film represents a distinct conception of the relationship between race and cinema, Gillespie recasts the idea of black film and poses new paradigms for genre, narrative, aesthetics, historiography, and intertextuality.


INTRODUCTION: In the last decade, over 800 disasters struck Latin America and the Caribbean, cumulatively affecting an estimated 64 million people. Three quarters of the region's population lives in disaster risk areas. There is widespread consensus that sexual violence increases in the aftermath of disasters, however historically its prevention has not been prioritized, and in general it remains a vastly understudied phenomenon at the intersection of health and human rights. The linkage between sexual violence and Human Immunodeficiency Virus (HIV) in the post-disaster context is similarly unrepresented in the literature. OBJECTIVES: This systematic review aims to assess the extent to which sexual violence in the post-disaster context has been studied in the region of Latin America and the Caribbean. The primary objectives of the review include (1) to identify and assess the quality of existing literature on sexual violence in the post-disaster context in Latin America and the Caribbean; (2) to assess whether ostensible increases in incidence of sexual violence and HIV infection in the post-disaster context are supported by the existing literature; and (3) to describe contextual factors of the post-disaster context that exacerbate sexual violence vulnerabilities. METHODS: A systematic review of the literature was conducted by searching PubMed, Ovid Global Health, Web of Science and LILACS databases for relevant publications on sexual violence in post-disaster Latin America and the Caribbean (n=147). Exclusion criteria were applied and 10 articles investigating the 2010 earthquake in Haiti (n=7), the 2007 earthquake in Peru (n=1), Hurricane Noel (2007) in the Dominican Republic (n=1), and Hurricane Mitch (1998) in Honduras and Nicaragua (n=1) were ultimately reviewed. RESULTS: The results of this systematic review indicate that sexual violence increases in the aftermath of natural disasters and that women and girls are the most vulnerable populations. Sexual violence may also increase risk of HIV, however there is insufficient evidence to support an association between sexual violence and HIV at the population level. Structural and social factors, most notably gender inequality, exacerbate sexual violence vulnerabilities in the postdisaster context. CONCLUSIONS: There is an urgent need for additional research investigating sexual violence in the global post-disaster context in order to inform prevention efforts and disaster preparedness and to uphold human rights. Funding: This project received no funding. Competing Interests: No competing interests exist. Acknowledgements I would like to thank Kate Nyhan, Research and Education Librarian at the Harvey Cushing/John Hay Whitney Medical Library at Yale, for her continuous support and expert advice during the literature search process. I would also like to thank my thesis advisor, Dr. Kaveh Khoshnood, for his support and encouragement.


A novel visually imperceptible image hiding scheme based on VQ compression and LSB modification is introduced in this article. Multiple secret images can be simultaneously and imperceptibly hid into another cover image with the same image size by the proposed scheme. In order to reduce the volume of secret images to be hid, a codebook is first generated form the secret images and these images are encoded into binary indexes by the vector quantization technique. Then the compressed data of secret images are embedded into the VQ codebook used in the encoding procedure by an adaptive least-significant-bits (LSB) modification technique. For the security purpose, the slightly modified codebook is further encrypted into a meaningless data stream by the DES cryptosystem. Finally, the encrypted codebook is embedded into the cover image using the greedy LSB modification technique. Simulation results show that the proposed scheme provides a good improvement in the visual quality of the extracted secret images and the cover image at the receiver. In addition, it also provides a better hiding capacity for the cover image.


Working with computational journalist Nick Diakopoulos, IEEE Spectrum has weighted and combined 12 metrics from 10 sources (including IEEE Xplore, Google, and GitHub) to rank the most popular programming languages. If you don?t agree with our weighting, want to see more languages, or are interested in what?s dominant in a specific subsector, such as mobile, go to our online interactive version. There you can adjust the weight of each metric and create your own custom ranking.


Progress in networking research depends crucially on applying novel analysis tools to real-world traces of network activity. This often conflicts with privacy and security requirements; many raw network traces include information that should never be revealed to others.The traditional resolution of this dilemma uses trace anonymization to remove secret information from traces, theoretically leaving enough information for research purposes while protecting privacy and security. However, trace anonymization can have both technical and non-technical drawbacks.We propose an alternative to trace-to-trace transformation that operates at a different level of abstraction. Since the ultimate goal is to transform raw traces into research results, we say: cut out the middle step. We propose a model for shipping flexible analysis code to the data, rather than vice versa. Our model aims to support independent, expert, prior review of analysis code. We propose a system design using layered abstraction to provide both ease of use, and ease of verification of privacy and security properties. The system would provide pre-approved modules for common analysis functions. We hope our approach could significantly increase the willingness of trace owners to share their data with researchers. We have loosely prototyped this approach in previously published research.


A rare but deadly form of human pancreatic cancer harbors mutations in chromatin remodeling genes. Pancreatic neuroendocrine tumors (PanNETs) are aggressive human cancers that often develop silently and progress to untreatable metastatic disease before diagnosis. Using an exome sequencing strategy to identify recurrent somatic mutations in PanNETs, Jiao et al. (see the Perspective by Elsässer et al.) find that the most commonly mutated genes, affecting nearly 45% of the tumors, encode proteins implicated in chromatin remodeling. About 15% of the tumors had mutations altering the mammalian target of rapamycin (mTOR) signaling pathway. mTOR inhibitors are already being tested as cancer therapies, so the mutational status of the PanNETs could help to identify which patients are most likely to respond to these drugs. Y. Jiao, C. Shi, B. H. Edil, R. F. de Wilde, D. S. Klimstra, A. Maitra, R. D. Schulick, L. H. Tang, C. L. Wolfgang, M. A. Choti, V. E. Velculescu, L. A. Diaz Jr., B. Vogelstein, K. W. Kinzler, R. H. Hruban, N. Papadopoulos, DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331, 1199–1203 (2011). [Abstract] [Full Text] S. J. Elsässer, C. D. Allis, P. W. Lewis, New epigenetic drivers of cancers. Science 331, 1145–1146 (2011). [Abstract] [Full Text]


An emerging body of data suggests that hypofractionated radiation schedules, where a higher dose per fraction is delivered in a smaller number of sessions, may be superior to conventional fractionation schemes in terms of both tumour control and toxicity profile in the management of adenocarcinoma of the prostate. However, the optimal hypofractionation scheme is still the subject of scientific debate. Modern computer-driven technology enables the safe implementation of extreme hypofractionation (often referred to as stereotactic body radiation therapy [SBRT]). Several studies are currently being conducted to clarify the yet unresolved issues regarding treatment techniques and fractionation regimens. Recently, the American Society for Radiation Oncology (ASTRO) issued a model policy indicating that data supporting the use of SBRT for prostate cancer have matured to a point where SBRT could be considered an appropriate alternative for select patients with low-to-intermediate risk disease. The present article reviews some of the currently available data and examines the impact of tracking technology to mitigate intra-fraction target motion, thus, potentially further improving the clinical outcomes of extreme hypofractionated radiation therapy in appropriately selected prostate cancer patients. The Champalimaud Centre for the Unknown (CCU)'s currently ongoing Phase I feasibility study is described; it delivers 45 Gy in five fractions using prostate fixation via a rectal balloon, and urethral sparing via catheter placement with on-line intra-fractional motion tracking through beacon transponder technology.


The global spread revolution of information and information technology is playing a decisive role to social change. Internet has become the most effective way for information transmission, whose role is network security. How to guarantee network security has become a serious and worrying problem. Biometric identification technology has some advantages including universality, uniqueness, stability and hard to be stolen. Through comparing with the other methods of biometric identification technology, such as fingerprint recognition, palm recognition, facial recognition, signature recognition, iris recognition and retina recognition, gene recognition has advantages of exclusiveness, never change, convenience and a large amount of information, which is thought to be the most important method of biometric identification technology. With the development of modern technology, the fusion of biological technology and information technology has become an inevitable trend. Biometric identification technology will necessarily replace the traditional identification technology and greatly change the life-style of people in the near future.


Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related neurodegenerative disorders and hence pose remarkable socio-economical burdens to both families and state. Although AD and PD have different clinical and neuropathological features, they share common molecular mechanisms that appear to be triggered by multi-factorial events, such as protein aggregation, mitochondrial dysfunction, oxidative stress (OS), and neuroinflammation, ultimately leading to neuronal cell death. Currently, there are no established and validated disease-modifying strategies for either AD or PD. Among the various lifestyle factors that may prevent or slow age-related neurodegenerative diseases, epidemiological studies on moderate consumption of red wine, especially as part of a holistic Mediterranean diet, have attracted increasing interest. Red wine is particularly rich in specific polyphenolic compounds that appear to affect the biological processes of AD and PD, such as quercetin, myricetin, catechins, tannins, anthocyanidins, resveratrol, and ferulic acid. Indeed, there is now a consistent body of in vitro and in vivo data on the neuroprotective effects of red wine polyphenols (RWP) showing that they do not merely possess antioxidant properties, but may additionally act upon, in a multi-target manner, the underlying key mechanisms featuring in both AD and PD. Furthermore, it is important that bioavailability issues are addressed in order for neuroprotection to be relevant in a clinical study scenario. This review summarizes the current knowledge about the major classes of RWP and places into perspective their potential to be considered as nutraceuticals to target neuropathology in AD and PD.


The current study aims to confine the prevalence rate of  Mycobacterium tuberculosis in suspected patients of district Mardan khaiber Pakhtunkhwa, Pakistan. It also aims to know about the pathogen of Mycobacterium tuberculosis and their pathogenicity in the host, mainly in human population of the district Mardan, to catch out the mode of transmission in the population of the suspected areas. One of the objectives of the study is to make people aware about the prevention and complete their treatment. District Mardan is one of the huge district of Khyber Pakhtunkhwa Pakistan where the new and relapse cases of tuberculosis found in high rate. Which have a great negative effect on the population of district Mardan. The research work done on the prevalence of tuberculosis in district Mardan in the period of October, November and December 2017. The overall 980 samples were registered in the different hospitals of Mardan area and examined by the use of sputum smear microscopy. A questionnaire has filled to collect data from patients which were include age, sex, area, marital status, diet, economic status, home condition, education, close contact to TB patients, drugs and awareness. In the selected sample the positive patients were 340 (34.69%) in which male were less prevalence 31.89% and female were high prevalence 37.44% that show that female have high rate of TB as compare to male due to the lack of education, awareness, and some other factors. The current study show that high prevalence 37.13% found in those patient who have lived in rural areas because of muddy houses, lack of education and dust in the rural areas. It also confined that high prevalence 42.10% found in the age range of 55 and above. It is noted that 32.77% of the suffering patients who were uneducated. Conclusion: The examination report display that the TB infection is high in the population of the district Mardan. It is also observed that the female are mostly suffered as compared to male. Treatment charges were the financial distressful constrictions challenged by TB patients therefore the role of government must be positive to provide TB drugs and perform many seminars for the people awareness.


Platelets were first described in the mid-nineteenth century. Since then, their roles were identified in hemostasis and thrombosis, inflammation, leukocyte interactions, angiogenesis, and cancer growth. But there is little information about such platelet functions in the newborn. Several studies highlighted some platelet differences between newborns and adults. Yet, in spite of these differences, healthy newborns appear to be adequately protected. A number of factors, however, were reported to negatively affect neonatal platelets. These include maternal hypertensive disorders or infections, neonatal asphyxia or respiratory distress, therapies such as ampicillin or indomethacin, and treatment modalities such as ventilators, nitric oxide, or extracorporeal membrane oxygenation (ECMO). Their effects on newborn platelets are usually transitory, lasting from several hours to a few days or weeks. If these effects are well characterized, they could serve as reporters for diagnosis and monitoring during therapy. Careful studies of neonatal platelets are needed to improve the understanding of basic physiology and pathophysiology in this cohort and to identify possible targets for intervention and therapy.


Quality of an open source software ecosystem (OSS ecosystem) is key for different ecosystem actors such as contributors or adopters. In fact, the consideration of several quality aspects(e.g., activeness, visibility, interrelatedness, etc.) as a whole may provide a measure of the healthiness of OSS ecosystems. The more health a OSS ecosystem is, the
more and better contributors and adopters it will gather. Some research tools have been developed to gather specific quality information from open source community data sources. However, there exist no frameworks available that can be used to evaluate their quality as a whole in order to obtain the health of an OSS ecosystem. To assess the health
of these ecosystems, we propose to adopt robust principles and methods from the Service Oriented Computing field.


A central hypothesis in sensory coding suggests that auditory neurons are optimized to represent sounds experienced by an organism in natural environments. In order to characterize the relationship between physical characteristics of natural sounds and their neural representation, we first quantified spectral and temporal modulations of a large ensemble of natural sounds that included animal vocalizations, human speech and environmental background sounds. We examined the neural responses to these sound cues in the central nucleus of the inferior colliculus (CNIC). We will demonstrate that neural filtering properties in the CNIC are optimized for encoding natural sounds in a manner that maximize power transfer across the ensemble of neurons. We next tested whether spectro-temporal sound preferences are hierarchically organized within the CNIC neural ensemble. A distinct laminar organization for sound frequency (tonotopy; Merzenich and Reid 1974; Semple and Aitkins 1979) and temporal modulation preferences (Schreiner and Langner 1988) has been previously demonstrated within the CNIC lamina; yet it is not clear whether higher-level spectral and temporal sound cues are systematically represented within the threedimensional volume of the CNIC. To test this hypothesis, we recorded neural responses to dynamic moving ripple sounds (Escabi and Schreiner 2002) with a 16 channel acute recording probe placed orthogonal to the isofrequency lamina of the CNIC. The probe spatial position was referenced to a three-dimensional coordinate system using a stereotaxic frame assembly. Each penetration was separated by 300μm along the laminar plane. This procedure allowed us to fully sample the threedimensional volume of the CNIC. Spectrotemporal receptive fields (STRF) were computed from the neural responses using reverse correlation procedures. We will show that the reconstruction of the spectro-temporal preferences along and across the isofrequency lamina exhibits a systematic organization for important acoustic parameters. Such a distributed organization has implications for how spectral and temporal features in natural sounds are encoded in the CNIC. In summary, these results provide evidence for an orderly neural representation of spectral and temporal sound cues that is consistent with efficiency coding principles.


A genetic system was developed in Escherichia coli to study leucine zippers with the amino-terminal domain of bacteriophage A repressor as a reporter for dimerization. This system was used to analyze the importance of the amino acid side chains at eight positions that form the hydrophobic interface of the leucine zipper dimer from the yeast transcriptional activator, GCN4. When single amino acid substitutions were analyzed, most fimctional variants contained hydrophobic residues at the dimer interface, while most nonfunctional sequence variants contained strongly polar or helix-breaking residues. In multiple randomization experiments, however, many combinations ofhydrophobic residues were found to be nonfunctional, and leucines in the heptad repeat were shown to have a special function in leucine zipper dimerization.


We develop a tractable model of strategic debt renegotiation in which businesses are sequentially interconnected through their liabilities. This financing structure, which we refer to as a debt chain, gives rise to externalities as a lender's willingness to provide concessions to his privately-informed borrower depends on how this lender's own liabilities are expected to be renegotiated. Our analysis reveals how targeted government subsidies and debt reductions as well as incentives for early renegotiation following large economic shocks such as COVID-19 or a financial crisis can prevent default waves.


Chinese legend has it that Pan Gu broke out of an egg, created the heavens and earth out of chaos (and egg parts), and stood on the earth to hold up the heavens. At the end of the Western 20th century, Pan Gu has been reborn as a serine-threonine kinase. The DNA replication block that follows meiosis is derepressed at fertilization, but just how the unfertilized ovum is prevented from entering S phase is largely a mystery. Fenger et al. have identified and characterized Pan Gu (PNG), which controls the onset of embryonic DNA synthesis in Drosophila. png is expressed only in the maternal ovaries and in embryos up to 3 hours after fertilization. Because plutonium (plu) mutants can enhance the phenotype evinced by weak png mutations (aberrant DNA synthesis and mitoses), the authors asked whether PNG and PLU (an ankyrin-repeat protein) associate. PNG immunoprecipitated with PLU; however, association was dependent on PNG kinase activity, suggesting that phosphorylation or the wild-type conformation of PNG was essential for coprecipitation. Additionally, association of PNG and PLU appeared indirect and was most likely mediated by an unknown adaptor protein, as PNG and PLU failed to associate in yeast two-hybrid experiments. PNG stabilized the levels of cyclin A and B, and led to higher levels of histone phosphorylation, presumably mediated by the kinase CDC2. These results suggest a mechanism whereby S phase is suppressed: by keeping mitotic kinases active (which prevent the activation of DNA replication origins), and maintaining chromatin in a highly condensed state (through histone phosphorylation), PNG may control the switch from mitosis to DNA synthesis in early Drosophila embryos. Fenger, D.D., Carminati, J.L., Burney-Sigman, D.L., Kashevsky, H., Dines, J.L., Elfring, L.K., and Orr-Weaver, T.L. (2000). PAN GU: A protein kinase that inhibits S phase and promotes mitosis in early Drosophila development. Development 127: 4763-4774. [Online Journal]


The Safavid era is of special significance in the history of Iran. Under the Safavids - between the sixteenth and the mid-eighteenth century - Iran was transformed and a state emerged which was the forerunner of the Iran of today in several important ways. The age is known for its wealth of contributions to Persian culture and to the arts of the Islamic world, its robust military encounters with its Ottoman and Mughal neighbours and growing contacts with Western Europe. But little is known about the social, cultural, commercial and diplomatic relations of the Safavids with the rest of the world. "Iran and the World in the Safavid Age" presents the most recent research into Safavid Iran's foreign relations. It challenges the long-held notion that, with the adoption of Shi'ism, Iranians retreated into relative isolation, suggesting rather that they engaged with the world in unprecedented and exciting ways. With contributions from the leading authorities in the field, Iran and the World in the Safavid Age explores Iran's relations with other countries and cultures. Examining how Iran was itself perceived as well as how it viewed the outside world this ground-breaking book sheds new light on the history of Iran's relations with the world beyond its borders and expands our understanding of this pivotal period.


Africa turned the corner of marginalization in international affairs at the beginning of the 21st century. The end of the Cold War and global shifts in power toward the end of the previous century were closely followed by "Africa rising." This contrasted previous decades-long narratives of a hopeless, war-ravaged, and plague-ridden continent. The Africa rising mantra followed reforms implemented in the late 1980s and early 1990s that improved institutional capacities and established African countries on firm business, economic, and political trajectories. This promised improved business environment, economic vitality, and positive democratic outlook.
 Africa has thus become important to major powers. They court it for its support to govern challenges that necessitate international cooperation and to enhance the major powers' influence in global institutions and on the world. Rising Asian economies such as China and India compete for Africa's natural resources against traditional global powers like the European Union (EU).
 The EU has long been economically and politically involved with Africa and has generally dominated these relations. Leading theories, discussions, and research that examine the historic, economic, and geopolitical factors at play in the evolution of African Union (AU)-EU relations suggest that elements of dependency are a calculated creation of colonialism and encounters that occurred between Africa and Europe before the advent of colonialism. Dependency continues to characterize these relations, as shown by formal AU-EU pacts. Decolonial scholars argue that the dependency is real, as Africa did not demolish colonial structures at independence. Some critical scholars further argue that the history of colonialism is also pertinent to the history of the EU in that the history of European integration was partly influenced by the history of colonialism. That is, the history of colonialism contributed to the political creation of the EU, and attempts by Western European countries to form a pan-European organization coincided with early 20th-century efforts to stabilize colonialism in Africa. The European countries could only efficiently exploit Africa by combining their political and economic capacities.
 AU-EU relations face many challenges in the 21st century. Influence in the relations is predominately unidirectional, with the EU determining the terms of engagement even on issues peculiar to Africa or the AU and where the latter appears to have the upper hand. The challenges show that the AU and EU are interdependent, but the onus is on the AU to set priorities right and enhance capabilities for engaging the EU. This would be easier if the EU were not continuously devising ways to maintain its dominance in the "partnership." An overarching challenge in the partnership, therefore, is finding common ground and leveling the playing field.


This thesis with the title:?Logical models of DNA damage induced pathways to cancer? was completed by Kun Tian for his PhD degree in the University of Manchester and submitted in October 2013. Chemotherapy is commonly used in cancer treatments, however only 25 % of cancers are responsive and a significant proportion develops resistance. The p53 tumour suppressor is crucial for cancer development and therapy, but has been less amenable to therapeutic applications due to the complexity of its action reflected in 67,000 papers describing its function. Here we provide a systematic approach to integrate this information by constructing large-scale logical models of the p53 interactome using extensive database and literature integration. Initially we generated models using manual curation to demonstrate the feasibility of the approach. This was followed by creation of the next generation models by automatic text mining results retrieval. Final model PKT205/G3 was generated by choosing the size of the interactome that could be analysed with current available computing power and by linking upstream nodes to input environmental signals such as DNA damage and downstream nodes to output signal such as apoptosis. This final version of the PKT205/G3 model contains 205 nodes representing genes or proteins, DNA damage input and apoptosis output, and 677 logical interactions. Predictions from in silico knock-outs and steady state model analysis were validated using literature searches and in vitro experiments. We identify an up regulation of Chk1, ATM and ATR pathways in p53 negative cells and 58 other predictions obtained by knockout tests mimicking mutations. The comparison of model simulations with microarray data demonstrated a significant rate of successful predictions ranging between 52 % and 71 % depending on the cancer type. Growth factors and receptors FGF2, IGF1R, PDGFRB and TGFA were identified as factors contributing selectively to the control of U2OS osteosarcoma and HCT116 colon cancer cell growth. In summary, we provide the proof of principle that this versatile and predictive model has vast potential for use in cancer treatment by identifying pathways in individual patients that contribute to tumour growth, defining a sub population of ?high? responders and identification of shifts in pathways leading to chemotherapy resistance.


Low soil fertility is a major constraint to maize production in the small holder farms of Meru South District. This is mainly attributed to the mining of nutrients due to cropping without external addition of adequate nutrients. Mineral fertilizers are expensive hence un affordable by most small holder farmers. The use of organic matter to increase and maintain soil fertility is being considered as a solution to help the lowincome small holder farmers. A study was conducted in Mucwa location, Meru South District to determine the levels of complementarity between organic and mineral N amendments on maize yields and their influence on soil chemical properties. The experiment was set in a complete randomized block design (CRBD) with three replicates. The treatments were compared with the response obtained from control. The general soil fertility parameters changed slightly with Calcium, Magnesium and Potassium increasing in all treatments. The organic Carbon and total Nitrogen was higher in treatments that received sole organic N sources than in sole mineral N and a combination of organic and mineral N sources. The highest maize grain yield of 4.8 t·ha −1 and 4.2 t·ha −1 were realized from sole application of calliandra during the 2005 Short rains and 2006 Long rains cropping seasons. Generally the maize grain yields were lower in treatments with mineral N alone compared to the treatments with organics. Treatments with sole calliandra and sole tithonia had the highest benefit cost ratio (BCR), followed closely by manure treatment. More so, integration of organic and mineral N sources resulted to higher net benefit and BCR than the application of the recommended rate of mineral fertilizers. Results obtained indicated that the use of either organic or combined organic/mineral N soil amendment appear to be superior to using mineral amendment sources alone.


ABSTRACT Some aspects of experience can be challenging for research participants to verbalise. Interpretative phenomenological analysis (IPA) researchers need to get experience-near to meet their phenomenological commitments, capturing the "texture" and quality of existence, and placing participants in relation to events, objects, others, and the world. Incorporating drawing into IPA designs provides a vehicle through which participants can better explore and communicate their lifeworlds. IPA researchers also require rich accounts to fulfil their interpretative commitments. Drawing taps into multiple sensory registers simultaneously, providing polysemous data, which in turn lends itself to hermeneutic analysis. This article outlines a multimodal method, the relational mapping interview, which was developed to understand the relational context of various forms of distress and disruption. We illustrate how the approach results in richly nuanced visual and verbal accounts of relational experience. Drawing on an "expanded hermeneutic phenomenology," we suggest how visual data can be analysed within an IPA framework to offer significant experiential insights.


Printing technologies have been demonstrated to be highly efficient and compatible with polymeric materials (both inks and substrates) enabling a new generation of flexible electronics applications. Conductive flexible polymers are a new class of materials that are prepared for a wide range of applications, such as photovoltaic solar cells, transistors molecular devices, and sensors and actuators. There are many possible printing techniques. This chapter provides an opportunity to review the most common printing techniques used at the industrial level, the most commonly used substrates and electronic materials, giving an overall vision for a better understanding and evaluation of their different features. Several technological solutions (contact/noncontact) and its critical challenges are also presented. Inkjet Printing Technology (IPT) has been receiving a great attention and therefore higher focus is given to this technology. An overview of IPT is presented to evidence its importance and potential as a key-technology on the research field for printed electronics development, as well as on large scale industrial manufacturing. A background and a review on prior work are presented along with used materials, developed applications and potential of IPT technology. The main features of the different printing technologies, advantages and main challenges are also compared.


In any 24 hours there might be sleeping, eating, kids, parents, friends, lovers, work, school, travel, deadlines, emails, phone calls, Facebook, Twitter, the news, the TV, Playstation, music, movies, sport, responsibilities, passions, desires, dreams. Why should you stop what you're doing and read a book? People have always needed stories. We need literature - novels, poetry - because we need to make sense of our lives, test our depths, understand our joys and discover what humans are capable of. Great books can provide companionship when we are lonely or peacefulness in the midst of an overcrowded daily life. Reading provides a unique kind of pleasure and no-one should live without it. In the ten essays in this book some of our finest authors and passionate advocates from the worlds of science, publishing, technology and social enterprise tell us about the experience of reading, why access to books should never be taken forgranted, how reading transforms our brains, and how literature can save lives. In any 24 hours there are so many demands on your time and attention - make books one of them. Carmen Callil, Tim Parks, Nicholas Carr, Michael Rosen, Jane Davis, Zadie Smith, Mark Haddon, Jeanette Winterson, Blake Morrison, Dr Maryanne Wolf & Dr Mirit Barzillai.


The projection method for constructing quasiperiodic tilings from a higher dimensional lattice provides a useful context for computing a quasicrystal's vertex configurations, frequencies, and empires (forced tiles). We review the projection method within the framework of the dual relationship between the Delaunay and Voronoi cell complexes of the lattice being projected. We describe a new method for calculating empires (forced tiles) which also borrows from the dualisation formalism and which generalizes to tilings generated projections of non-cubic lattices. These techniques were used to compute the vertex configurations, frequencies and empires of icosahedral quasicrystals obtained as a projections of the D 6 and Z 6 lattices to R 3 and we present our analyses. We discuss the implications of this new generalization.


We adopted an integrated systematic approach to delimit evolutionary species and describe phylogeographic, morphometric and ecological relationships in Otomys denti (from the Albertine Rift, Southern Rift in Malawi and the northern Eastern Arc Mountains) and Otomys lacustris (from the Southern Rift in Tanzania and Zambia, and the southern Eastern Arc Mountains). Molecular [cytochrome (cyt) b sequences, 1143 bp, N = 18], craniometric (classical, N = 100 and geometric, N = 60) and ecological (Partial Least Squares regression of shape and ecogeographic variables) approaches show a profound, parallel disjunction between two groups: (1) Eastern Arc and Southern Rift (including the Malawi Rift) (O. lacustris and Otomys denti sungae) and (2) Albertine Rift (Otomys denti denti and Otomys denti kempi) taxa. Within both groups, cyt b sequences or craniometric analysis provided evidence for the differentiation of both southern and northern Eastern Arc from Southern Rift lineages (across the so-called Makambako Gap). Within the Albertine Rift (denti–kempi) lineage, populations from individual mountain ranges differed significantly in skull shape (but not size), but were similar genetically. Over-reliance in the past on very few morphological characters (e.g. number of molar laminae) and a polytypic species concept has obscured phylogenetic relationships and species discrimination in this group. We recognize at least three species in this group, and distinct lineages within two of these species. Each species or lineage was endemic to one of three regions: the Albertine Rift, the Malawi Rift or the Eastern Arc. Our result echo conclusions of recent studies of other mammalian and bird taxa and reflect the geomorphology and palaeoclimatic history of the region. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 96, 913–941.


The purpose  of the study was to determine teachers' opinions about virtual reality (VR). Virtual Reality Interview Form (VRIF) administered to seven teachers after the implementation of VR practices. Teachers received three weeks of intensive training. Afterward, teachers applied VR for two months in their classrooms. Later, interviews held with them. Findings indicated that different VR practices, including Google Cardboard, were used in the classroom. According to the teachers, using virtual reality in the classroom captured students' interest, increased their creativity, allowed students to take virtual trips, increased students' motivation, improved students' technology literacy, individualized learning; made students easier to understand difficult concepts. The potential problems of using VR were not asked the teachers; however, teachers mentioned that online safety and security, student access, and technology gaps were the problems they faced. The findings of this study suggest that the use of VR allows teachers to visualize abstract topics and enrich instruction. A VR orientation module would be provided teachers with opportunities to learn, practice, and apply their VR skills before being placed in the classroom.


Consider an unweighted k-nearest neighbor graph on n points that have been sampled i.i.d. from some unknown density p on ℝd. We prove how one can estimate the density p just from the unweighted adjacency matrix of the graph, without knowing the points themselves or any distance or similarity scores. The key insights are that local differences in link numbers can be used to estimate a local function of the gradient of p, and that integrating this function along shortest paths leads to an estimate of the underlying density.


Childhood food allergies regularly cause distress to children and their parents. At one extreme, there are the severe and potentially dangerous nut-related allergies or even hyperactivity. At the other, the mild discomfort of a sensitive stomach. Some children grow out of the problem; others need to discover a way of eating that they will follow for the rest of their lives. In either case, parents need sound, practical advice on how to tackle the problem, with a varied bank of recipes for all occasions that combines good nutritional balance with great eating. That's what this useful and practical book provides.


One important effect of the sluggish IPO market is the focus on deregulation and the emergence of a new generation of securities markets. These deregulated markets are considered important to stimulate entrepreneurial activity and attract venture capital. This paper argues that the introduction of these new markets and accompanying deregulatory measures exhibits a surprisingly low success rate.There are several reasons for this. First, founders of emerging growth companies increasingly believe that it is in their best interest to remain private as long as possible. Second, we show how the decline of IPOs has led venture capitalists and entrepreneurs to access other exit routes. Trade sales have become the preferred exit option for most investments in growth companies. Third, we observe that mature corporations show an increased interest in hiring or collaborating with venture capitalists (to improve the innovation outcomes of the mature corporations). Fourth, by using case illustrations from the corporate venture capital industry, we highlight the wide variety of new collaborative venture capital models (which will arguably pave the way to even more trade sales with higher exit values in the future).


Traditionally, the core of a Termino-logical Knowledge Representation System (TKRS) consists of a so-called TBox, where concepts are introduced, and an ABox, where facts about individuals are stated in terms of these concepts. This design has a drawback because in most applications the TBox has to meet two functions at a time: on the one hand, similar to a database schema, framelike structures with typing information are introduced through primitive concepts and primitive roles; on the other hand, views on the objects in the knowledge base are provided through de-ned concepts. We propose to account for this conceptual separation by partitioning the TBox into two components for primitive and deened concepts, which we call the schema and the view part. We envision the two parts to diier with respect to the language for concepts , the statements allowed, and the semantics. We argue that by this separation we achieve more conceptual clarity about the role of primitive and deened concepts and the semantics of terminological cycles. Moreover, three case studies show the computational beneets to be gained from the reened architecture.


In this presentation I will show my preliminary results from a research project about collaborative language learning in an academic online course in German. The study is based on a sample of 35 chat-logs from 30 students of different language background (Swedish or German as L1) and different levels of German proficiency, working on collaborative tasks in equal and unequal formations of triads or dyads. The data was collected in four of eight online seminars which were an obligatory part of a German literature course at a Swedish university. These seminars were conducted in private chatrooms in MSN/Adobe connect. The students had to answer open-ended questions about the literature they had read, which they had prepared in advance. The results indicate that Swedish students with a lower level of German proficiency produce longer messages when interacting in formations with native speakers than with peers. On the other hand, interactional modifications or scaffolding where the attention was directed on form or meaning of the L2 overall occurred only to a small extend. This means that learners only get few opportunities to develop new L2 knowledge with the help of experts, a condition which is thought essential by researchers within a cognitive or sociocultural learning approach. Further study of the data reveals that the students frequently make use of imitation of whole utterances or parts of utterances of their collocutors. This strategy may help them to become more fluent in German and may also assist the development of more complex structures of the L2.


Detachment faults on the west flank of the Black Mountains (Nevada and California) dip 29°-36° and cut subhorizontal layers of the 0.77 Ma Bishop ash. Steeply dipping normal faults confined to the hanging walls of the detachments offset layers of the 0.64 Ma Lava Creek B tephra and the base of 0.12-0.18 Ma Lake Manly gravel. These faults sole into and do not cut the low-angle detachments. Therefore the detachments accrued any measurable slip across the kinematically linked hanging-wall faults. An analysis of the orientations of hundreds of the hanging-wall faults shows that extension occurred at modest slip rates (<1 mm/yr) under a steep to vertically oriented maximum principal stress. The Black Mountain detachments are appropriately described as the basal detachments of near-critical Coulomb wedges. We infer that the formation of late Pleistocene and Holocene range-front fault scarps accompanied seismogenic slip on the detachments.


Background: Discharging effluents containing heavy metals is very harmful due to accumulative property and non-biodegradability of them. Electrocoagulation, due to easy operation and less chemical consumption, is being considered as a process for removal of heavy metals from aqueous environments.
Objective: The aim of the study was to evaluate the effects of variables influencing the removal of
cadmium from aqueous environment during electrocoagulation and to develop a model for predicting
the results.
Methods: This experimental study was performed in a batch electrocoagulation reactor using aluminum electrodes. Direct current was supplied using D.C power supply. Cadmium concentrations were measured using standard methods for the examination of water and wastewater. Response surface methodology and central composite design were used to determine the effects of variables (pH, initial concentration of cadmium, electric current density, reaction time and distance between electrodes) on the removal of cadmium, to design the experiments, to prepare the prediction model for cadmium removal and to optimize the variables.
Findings: The optimal removal efficiency in the conditions of pH; 8.32, current density; 2.965mA/cm2,
initial concentration; 65.5 mg/L, reaction time; 54 min and distance between electrodes: 0.723cm was 97.5%. Also R2, Adj.R2 and Pred. R2 were 0.98, 0.97 and 0.96, respectively, which indicates a good fit of the data on quadratic equations. The interactions of all variables were significant in the removal of cadmium by electrocoagulation. The quadratic model is a suitable model for predicting the removal of cadmium using electrocoagulation.
Conclusion: Electrocoagulation equipped with aluminum electrodes has high performances in cadmium removal from aqueous environment. This process can be used in primary or supplementary treatment of industrial wastewater containing this heavy metal.


Twelve volumes kept in the Archives and documentation department of the Ministry of Foreign affairs in Paris. They comment on the power of the last Kotugawa Shogun an observation at first hand by the French diplomat, following reflexions upon the Japanese documents which had been essential to administration of Edo. These texts are annexed to a thematic consideration of the most serious infractions of the frano-japanese tresty of the 9 October 1858, and illustrate some of the principal events which marked the period of crisis which the Shogunate experienced for reason, notably, the initiatives taken by the representatives of the powers which were signatories to treaties with Japan, many notes and documents treat with the intenal politics of Japan, vis-a-vis the Foreigners.


Although oral dental tissue is a vertebrate attribute, trunk dental tissue evolved in several extinct vertebrate lineages but is rare among living species. The question of which processes trigger dental-tissue formation in the trunk remains open, and would shed light on odontogenesis evolution. Extra-oral dental structures (odontodes) in the trunk are associated with underlying dermal bony plates, leading us to ask whether the formation of trunk bony plates is necessary for trunk odontodes to emerge. To address this question, we focus on Loricarioidei: an extant, highly diverse group of catfish whose species all have odontodes. We examined the location and cover of odontodes and trunk dermal bony plates for all six loricarioid families and 17 non-loricarioid catfish families for comparison. We inferred the phylogeny of Loricarioidei using a new 10-gene dataset, eight time-calibration points, and noise-reduction techniques. Based on this phylogeny, we reconstructed the ancestral states of odontode and bony plate cover, and find that trunk odontodes emerged before dermal bony plates in Loricarioidei. Yet we discovered that when bony plates are absent, other surface bones are always associated with odontodes, suggesting a link between osteogenic and odontogenic developmental pathways, and indicating a remarkable trunk odontogenic potential in Loricarioidei.


We examine price by season and by year in 14 deregulated markets, by looking at diurnal price patterns and price volatility. Power price volatility is measured by price velocity, the daily average of the absolute value of price change per hour, which is broken into a component expected from the average diurnal pattern, and an unexpected component. Deregulated markets can be categorized into three groups: stable markets, markets that experienced one bad period or season of high price excursion, and chaotic markets. Britain, Spain and Scandinavia show consistent price patterns and low unexpected price velocity; a thoughtful consumer could reasonably implement demand side management (DSM) by shaping consumption patterns to reflect price. California, New Zealand and Alberta are examples of markets that had a period of very high price excursion; we discuss factors affecting public reaction to this. Australian power markets have inconsistent price patterns from season to season and year to year, and very high unexpected price velocity. Planned DSM in these markets would be very difficult. We offer four policy considerations for markets considering deregulation in the future.


Following the success of its all-male refugee football team, the Italian voluntary-based association Liberi Nantes created a touch rugby team as a pilot project aimed at involving female forced migrants. Initially set up as an all-woman activity to provide a less intimidating environment, the touch rugby group was later turned into a mixed-sex team. While potentially enabling transformative experiences and generating opportunities for
challenging gender stereotypes, the mixed-gender character of the touch rugby provision also served broader objectives within Liberi Nantes' mission. Focusing on the accounts of the activists and volunteers involved in the project, this paper investigates the practical and symbolic reasons for the strategic use of mixed-gender sport and its implications. Notably, by analysing the development of the touch rugby team, we highlight how its mixed-gender nature contributes to nourishing a wider rhetoric of social mixing and celebration of diversity, in which Liberi Nantes' identity is embedded.


This study presents a modified continuum model to investigate the vibration behavior of single and multi-carbon nanotubes (CNTs). Two parameters are exploited to consider size dependence; one derived from the energy equivalent model and the other from the modified couple stress theory. The energy equivalent model, derived from the basis of molecular mechanics, is exploited to describe size-dependent material properties such as Young and shear moduli for both zigzag and armchair CNT structures. A modified couple stress theory is proposed to capture the microstructure size effect by assisting material length scale. A modified kinematic Timoshenko nano-beam including shear deformation and rotary inertia effects is developed. The analytical solution is shown and verified with previously published works. Moreover, parametric studies are performed to illustrate the influence of the length scale parameter, translation indices of the chiral vector, and orientation of CNTs on the vibration behaviors. The effect of the number of tube layers on the fundamental frequency of CNTs is also presented. These findings are helpful in mechanical design of high-precision measurement nano-devices manufactured from CNTs.


This paper investigates how spin-offs affect capital allocation decisions in diversified firms. The sensitivity of capital expenditures to investment opportunities, representing the efficiency of capital allocation decisions, improves when firms undertake spin-offs. The improvement in the efficiency of capital allocation decisions is most pronounced immediately following the completion of spin-offs (though it attenuates thereafter) and in companies that operate in a moderate (as opposed to a high or a low) number of businesses pre-spin-off. Together, these findings uncover a novel benefit that is associated with spin-offs, an improvement in the process by which managers allocate capital in the divesting firms. These results also suggest that an important theoretical mechanism that may be driving this improvement is that spin-offs enable managers to devote more attention to the capital allocation process within their remaining businesses.


Composites consisting of metal nanoparticles (NPs) embedded in dielectric media may present large nonlinear optical response due to electronic transitions in the NPs. When the metal NPs are suspended in liquids or embedded in solid substrates, the obtained composites may present high-order optical nonlinearities (HON) beyond the third-order nonlinearity, usually studied for most materials. Moreover, it is observed that the magnitude and phase of the effective high-order susceptibilities can be controlled by adjusting the light intensity, I, and the volume filling fraction, f, occupied by the NPs. Therefore, the sensitivity to the values of I and f allowed the development of a nonlinearity management procedure for investigation and control of various phenomena, such as self- and cross-phase modulation, spatial modulation instability, as well as bright and vortex solitons stabilization, in media presenting relevant third-, fifth-, and seventh-order susceptibilities. As a consequence, it is reviewed in this paper how the exploitation of HON in metal–dielectric nanocomposites may reveal new ways for optimization of all-optical switching devices, light-by-light guiding, as well as the control of solitons propagation for long distances. Also, theoretical proposals and experimental works by several authors are reviewed that may open the possibility to identify new high-order phenomena by applying the nonlinearity management procedure. Therefore, the paper is focused on the properties of metal nanocomposites and demonstrates that these plasmonic composites are versatile platforms for high-order nonlinear optical studies.


A parameter-extraction approach for the quantum- well laser, which combines the analytical approach and the empirical optimization procedure, is developed in this paper. The initial values of the parasitic pad capacitance and the feedline inductance are extracted by using a set of closed-form expressions derived from above-threshold mode input reflection coefficient on wafer measurement, and the extrinsic contact resistance and capacitance determined by using the analytical method are described as functions of the parasitic pad capacitance and the feedline inductance. Advanced Design System (Agilent commercial software) is then used to optimize only the parasitic pad capacitance and the feedline inductance with very small dispersions of initial values. An excellent fit between measured and simulated input reflection coefficients under cutoff and above-threshold biased conditions in the frequency range of 50 MHz-40 GHz is obtained.


Recent progress in deep learning is revolutionizing the healthcare domain including providing solutions to medication recommendations, especially recommending medication combination for patients with complex health conditions. Existing approaches either do not customize based on patient health history, or ignore existing knowledge on drug-drug interactions (DDI) that might lead to adverse outcomes. To fill this gap, we propose the Graph Augmented Memory Networks (GAMENet), which integrates the drug-drug interactions knowledge graph by a memory module implemented as a graph convolutional networks, and models longitudinal patient records as the query. It is trained end-to-end to provide safe and personalized recommendation of medication combination. We demonstrate the effectiveness and safety of GAMENet by comparing with several state-of-the-art methods on real EHR data. GAMENet outperformed all baselines in all effectiveness measures, and also achieved 3.60% DDI rate reduction from existing EHR data.


This paper proposes an optical wireless transfer agent method which realizes the continuous and swift data transfer of optical wireless terminals in optical wireless networks. The unguided wireless channel generally shows frequent link disconnections and propagation delays due to weak wireless links. Specially speaking, optical wireless channels have more vulnerable links and roaming propagation delays relative to the weakness of the previous RF channels due to their low signal connectivity and small geographic coverage. Conventional optical wireless network protocols did not consider any fault models about physical link faults. Consequently, they have shown data transfer inefficiency for both data link control and physical wireless link control. To overcome these optical wireless environmental problems, this paper suggests a new wireless access point (or base station) agent system, which provides wireless or mobile clients with previous link layer protocols compensated.


The Pim protein kinases play important roles in cancer development and progression, including prostate tumors and hematologic malignancies. To investigate the potential role of these enzymes as anticancer drug targets, we have synthesized novel benzylidene-thiazolidine-2,4-diones that function as potent Pim protein kinase inhibitors. With IC50 values in the nanomolar range, these compounds block the ability of Pim to phosphorylate peptides and proteins in vitro and, when added to DU145 prostate cancer cells overexpressing Pim, inhibit the ability of this enzyme to phosphorylate a known substrate, the BH3 protein BAD. When added to prostate cancer cell lines, including PC3, DU145, and CWR22Rv1, and human leukemic cells, MV4;11, K562, and U937 cells, these compounds induce G1-S cell cycle arrest and block the antiapoptotic effect of the Pim protein kinase. The cell cycle arrest induced by these compounds is associated with an inhibition of cyclin-dependent kinase 2 and activity and translocation of the Pim-1 substrate p27Kip1, a cyclin-dependent kinase 2 inhibitory protein, to the nucleus. Furthermore, when added to leukemic cells, these compounds synergize with the mammalian target of rapamycin inhibitor rapamycin to decrease the phosphorylation level of the translational repressor 4E-BP1 at sites phosphorylated by mammalian target of rapamycin. Combinations of rapamycin and the benzylidene-thiazolidine-2,4-diones synergistically block the growth of leukemic cells. Thus, these agents represent novel Pim inhibitors and point to an important role for the Pim protein kinases in cell cycle control in multiple types of cancer cells. [Mol Cancer Ther 2009;8(6):1473–83]