Background: Hypertension is one of the largest health burdens in the world, leading to stroke, coronary heart disease, myocardial infarct, peripheral artery disease (PAD) and renal failure. There are many pharmaceutical medications on the market for blood pressure management. Many of these medications have undesirable side effects or are expensive. Dietary intervention with omega-3 fatty acids has become a popular alternative to medication for blood pressure (BP) control. The cardiovascular benefits of omega-3 fatty acids consumed via fish oil have been well established. More research is being done to establish the mechanism and efficacy of other dietary sources containing fatty acids. It has been suggested that foods high in alpha-linolenic acid (ALA) may have cardio protective properties. Dietary flaxseed is one of the foods of interest being it contains the highest level of ALA. Although the mechanisms are not fully understood, dietary flaxseed may be an effective and safe alternative for BP management. Methods: An exhaustive search was conducted using Medline-OVID, CINAHL, and Web of Science using the keywords: flax, flaxseed, linseed oil, blood pressure, and hypertension. Relevant articles were assessed for quality using GRADE. A search on the NIH clinical trials site reveals there is one trial currently registered relating to the antihypertensive effects of dietary flaxseed. Results: Two studies met the search criteria and were included in this systematic review. The first study, FLAX-PAD, was a double blind, placebo-controlled, randomized controlled study (RCT) utilized to examine the effects of dietary flaxseed on systolic BP and diastolic BP in patients newly diagnosed with PAD. This study demonstrated the antihypertensive effects in patients consuming dietary flaxseed. Researchers also revealed the relationship between plasma ALA levels and blood pressure. The second study was a prospective, two-group, parallel-arm design RCT to examine the effects of dietary flaxseed on blood pressure in middleaged dyslipidemic men. This study revealed a significant reduction in blood pressure in individuals receiving the intervention. Conclusion: Daily consumption of 30g of milled flaxseed or 15mL of flax oil per day has shown an antihypertensive effect on select patient populations. The latest studies regarding flaxseed and its antihypertensive effects seem promising, but further randomized controlled trials are needed to clearly establish its efficacy. Degree Type Capstone Project Degree Name Master of Science in Physician Assistant Studies


Global commitment to malaria control has greatly increased over the last decade. Long-lasting insecticidal nets (LLINs) have become a core intervention of national malaria control strategies and over 450 million nets were distributed in sub-Saharan Africa between 2008 and 2012. Despite the impressive gains made as a result of increased investment in to malaria control, such gains remain fragile. Existing funding commitments for LLINs in the pipeline to 2016 were collated for 40 sub-Saharan African countries. The population-based model NetCALC was used to estimate the potential LLIN coverage achievable with these commitments and identify remaining gaps, and the Lives Saved Tool (LiST) was used to estimate likely consequences for mortality impact if these gaps remain unfilled. Overall, countries calculated a total need of 806 million LLINs for 2013-16. Current funding commitments meet just over half of this need, leaving approximately 374 million LLINs unfunded, most of which are needed to maintain coverage in 2015 and 2016. An estimated additional 938,500 child lives (uncertainty range: 559,400–1,364,200) could be saved from 2013 through 2016 with existing funding (relative to 2009 LLIN coverage taken as the 'baseline' for this analysis); if the funding gap were closed this would increase to 1,180,500 lives saved (uncertainty range: 707,000–1,718,900). Overall, the funding gap equates to approximately 242,000 avoidable malaria-attributable deaths amongst under-fives. Substantial additional resources will need to be mobilized to meet the full LLIN need of sub-Saharan countries to maintain universal coverage. Unless these resources are mobilized, the impressive gains made to date will not be sustained and tens of thousands of avoidable child deaths will occur.


Urban search and rescue missions raise special requirements on robotic systems. Small aerial systems provide essential support to human task forces in situation assessment and surveillance. As external infrastructure for navigation and communication is usually not available, robotic systems must be able to operate autonomously. A limited payload of small aerial systems poses a great challenge to the system design. The optimal tradeoff between flight performance, sensors, and computing resources has to be found. Communication to external computers cannot be guaranteed; therefore, all processing and decision making has to be done on board. In this article, we present an unmanned aircraft system design fulfilling these requirements. The components of our system are structured into groups to encapsulate their functionality and interfaces. We use both laser and stereo vision odometry to enable seamless indoor and outdoor navigation. The odometry is fused with an inertial measurement unit in an extended Kalman filter. Navigation is supported by a module that recognizes known objects in the environment. A distributed computation approach is adopted to address the computational requirements of the used algorithms. The capabilities of the system are validated in flight experiments, using a quadrotor.


Coal is the prime source of energy in India. Opencast mining of coal damage a large land surface area, displace people from their natural home and cause agricultural losses. This raises a number of environmental challenges, including soil erosion, dust, noise, and water pollution impacts on local biodiversity. Generation of dump waste from opencast mines in Jharia coalfield threatens the social sustainability of land use pattern in many ways. The overburden dumps formed outside the open pits besides occupying the lands alter the surface topography and contribute to the environmental degradation. In the present paper authors have attempted to study the impact of physical properties of soil and his effect on the growth of some selected grasses over mine dumps. Bulk density plays a significant role in growth of selected grasses as observed during this experiment.


Labor Market Regulation and its Characteristics: Comparison Between Czech Republic and Austria In this paper, we are trying to compare the labor market regulation in the Czech Republic and Austria and its structural parameters that characterize the given labor markets. In order to do that, we estimate the New-Keynesian model with matching frictions and nominal wage rigidities. Labor market regulation is proxied by worker's bargaining power over the wage. This main parameter is moving inside the interval and express a share of the total surplus that arises from filling the vacancy. In fact it expresses the state of who gains more from the added value that the vacancy is filled (worker or employer). Results indicate that workers in Austria and the Czech Republic have almost the same bargaining power that arises from the labor market settings.


Part 1 of this two-part article reviewed the four main doctrines to which Canadian courts have referred in interpreting the Income Tax Act (strict construction, purposive interpretation, the plain meaning rule, and the words-in-total-context approach) and examined leading cases in which these doctrines have been defined and applied. Part 2 of the article evaluates each of the interpretive doctrines examined in part 1 and develops, as an alternative, an explicitly "pragmatic" approach. This alternative approach builds on the words-in-total-context doctrine by interpreting the words of the Act "in their entire context," having regard to the scheme of the Act, the purposes of the Act, the intentions of Parliament, and the practical consequences of different interpretations.Following the analysis of the four doctrines, the article outlines the essential features of an explicitly pragmatic approach to statutory interpretation, explains the relevance of practical consequences to judicial decisions, and considers the manner in which consequential considerations and other relevant factors are properly brought together in the context of a particular interpretive issue. Emphasizing the significance of textual, purposive, and consequential considerations to statutory interpretation, this interpretive approach favours an open and inquiring method of judicial reasoning by which the court should endeavour, where possible, to fashion a mutual harmony among these various interpretive elements. Where this harmony is ultimately unachievable, however, the pragmatic approach advocated here follows the traditional practice of English, US, and Canadian courts by generally weighing textual considerations more heavily than purposive considerations and purposive considerations more heavily than consequential considerations.To the extent that Supreme Court of Canada decisions interpreting the Income Tax Act already examine textual, purposive, and consequential considerations, the pragmatic approach advocated here is not so much a departure from the court's actual practice of statutory interpretation as a more satisfactory account of that practice than is provided by the various doctrines to which the court now refers. To the extent that these doctrines shape both the process of statutory interpretation and the substance of the decisions themselves, however, the proposed pragmatic approach promises a more open, reasoned, and balanced method of statutory interpretation than each of the alternatives otherwise available.Reproduced with the permission of the Canadian Tax Foundation


When 2 leaders in the healthcare field, coming from entirely different perspectives, arrive at the same conclusion, it's time to pay attention. Please allow me to explain. Lawrence P. Casalino, MD, PhD, is the Livingston Farrand Associate Professor of Public Health and Chief of the Division of Outcomes and Effectiveness Research at the Weill Cornell Medical College in New York City. Dr Casalino has been a prolific contributor to the literature in health services research and our paths have crossed several times, most recently when we cohosted a Commonwealth Fund's Harkness Fellow from the United Kingdom.

Jeffrey Brenner, MD, has risen to national prominence as a recent MacArthur Fellow Genius Grant awardee, as well as the Executive Director and Founder of the Camden Coalition of Healthcare Providers, a nonprofit organization committed to delivering better care at lower costs in Camden, NJ, one of America's poorest cities.

In their separate, recent publications, they came to the identical conclusion. Dr Casalino's article was published by the Agency for Healthcare Research and Quality (AHRQ) in February 2014, and was based on a February 2011 presentation at an AHRQ conference entitled, "The Challenge and Promise of Delivery System Research."1 Dr Brenner's conclusion was written in his GrantWatch blog dated February 18, 20142—within days of the publication of Dr Casalino's article.

Despite spending hundreds of billions of dollars in biomedical research, which is largely funded through the National Institutes of Health (NIH), and spending nearly 18% of the US gross domestic product (the world's largest economic engine) on healthcare, we still have "little understanding of how to deliver better care at lower cost to every American … and we do not understand the fundamental drivers of healthcare utilization; the basic rules for designing and implementing effective interventions; the best ways to use data to plan, implement, manage, and evaluate interventions; nor how to train staff to run and lead these interventions."2

In his AHRQ synthesis article, Dr Casalino expresses pretty much the same idea, but he obviously has to cast it in a different light, because of the support from the AHRQ. In his article, he concludes that, "the discoveries of basic scientific and clinical research have no impact on patients' health unless they are used effectively by the healthcare delivery system."1 To improve quality and to contain costs, Dr Casalino recommends that "research should focus on (1) identifying the types of organizations that are high performing; (2) identifying the types of incentives that induce these organizations to continually improve care; and (3) identifying the types of incentives likely to lead to the creation of more high-performing organizations and to physicians and other providers becoming members of high-performing organizations."1

I think Dr Brenner and Dr Casalino would agree that it is the culture that makes the difference, and a core component of the culture is the leadership that motivates these organizations. In other words, although the awesome biomedical research engine represented by the NIH and the health services research engine represented by the AHRQ are certainly the envy of the world, what value do we have to show for this investment? When the United States ranks number 17 in the world (behind Slovenia) with regard to the quality of life of our citizenry, I would argue that we have not achieved a great return on this sizable investment.3

We need a new type of research framework. The questions become what should be the components of this research framework, and who ought to drive it?

Dr Casalino eloquently describes what the components of the new research framework should be. He has gone so far as to establish the criteria for selecting the priority areas for delivery system research, and these are detailed in his article.1 It should come as no surprise to our readers that Dr Casalino considers the critical framework to involve an evaluation of accountable care organizations, patient-centered medical homes, and other components of the Affordable Care Act. I have discussed many aspects of this exact challenge in this column previously. Dr Casalino goes on to ask probing framework-like questions regarding "what effects, if any, does the structure, process, or incentive have on areas for care not directly related to it? For example, do large organizations score better on typical measures of quality but not on areas of quality that are not typically measured (eg, timely diagnosis)?"

I concur with most of the framework discussion articulated by Dr Casalino. So where should this new work occur, and who should support it? Dr Brenner is seeking a "scientific revolution of better care at lower cost," and he declares that the revolution will not be led by academic health centers alone, because they are at risk of losing too much.2 He believes that "the underpinnings of their financial model would collapse if their unneeded bed capacity went occupied." Finally, Dr Brenner proposes that the creation and support of industrial population health research laboratories in disparate locations across the country be funded by private foundations. This industrial population health resource, as he describes it, would be led by community-wide, nonprofit organizations with broad stakeholder and community support. Local hospitals may be participants in this process.2

I have tremendous respect for both Dr Casalino and Dr Brenner. I believe that they have come, largely, to the same conclusion—it is the system. We desperately need more insight as to what will deliver the greatest care at the highest level of value to the largest number of patients. However, I do not agree with Dr Brenner that a local coalition of not-for-profit organizations is going to make it work. Nor do I agree with Dr Casalino that more AHRQ funding is the answer to gaining a better understanding of the culture and leadership. I think they are both off the mark in this regard.

My own view is to "let 1000 flowers bloom." Let the private sector, driven by powerful and inexorable market forces, recreate the healthcare system. Let private organizations build the platforms to create population health registries, create the companies that will deliver economic incentives for patients to change their behavior, and ultimately, and perhaps in a messy way, we will get to a population health agenda that our nation so desperately deserves.

As always, I am interested in your views, and you can reach me via e-mail at email@example.com.


SUMMARY Innovation platforms are fast becoming part of the mantra of agricultural research for development projects and programmes. Their basic tenet is that stakeholders depend on one another to achieve agricultural development outcomes, and hence need a space where they can learn, negotiate and coordinate to overcome challenges and capture opportunities through a facilitated innovation process. Although much has been written on how to implement and facilitate innovation platforms efficiently, few studies support ex-ante appraisal of when and for what purpose innovation platforms provide an appropriate mechanism for achieving development outcomes, and what kinds of human and financial resource investments and enabling environments are required. Without these insights, innovation platforms run the risk of being promoted as a panacea for all problems in the agricultural sector. This study makes clear that not all constraints will require innovation platforms and, if there is a simpler and cheaper alternative, that should be considered first. Based on the review of critical design principles and plausible outcomes of innovation platforms, this study provides a decision support tool for research, development and funding agencies that can enhance more critical thinking about the purposes and conditions under which innovation platforms can contribute to achieving agricultural development outcomes.


In this work a new image sharpening technique based on multiscale analysis and wavelet fusion is presented. The proposed technique is suitable for visibility optimization of biomedical images obtained from MRI sensors. The proposed approach combines, with a wavelet based fusion algorithm, the sharpening results accrued from a number of independent image sharpening techniques. Initially, the input image is preprocessed by a denoising filter based on a complex Two Dimensional Dual-Tree Discrete Wavelet Transform. Then, the denoised image is passed through a cluster of five sharpening filters and subsequently, the final image is obtained with the help of a wavelet fusion technique. The main novelty of the proposed technique lies on using only one input image for sharpening and that the fusion is performed on images extracted in different frequency bands. This technique could be used as a preprocessing step in many applications. In this paper we focus on the application of the proposed technique in brain MR images. Specific image sharpening and quality indices are employed for the quantitative assessment of the proposed technique


When James Buchanan took office the United States was sound financially. The treasury was running in the black as revenues of the federal government exceeded expenditures. Buchanan recommended that these monies be spent on great national projects such as increased naval construction to protect our vast tonnage afloat which was greater than any other nation or extinguishing the national debt. Being a die-hard Jacksonian on economic issues, he believed that revenues should match and not exceed expenditures. When the panic of 1859 hit, Buchanan utilized a blend of monetary and fiscal policies to remedy the situation.


Abstract : Every machine vibrates and emits noise. This is unused energy that, with an appropriate mechanism, can be returned to the system. Utilizing an array of piezoelectric microelectromechanical systems (MEMS) devices to harvest this otherwise wasted energy, it is possible to improve the efficiency of any number of mechanical devices. Piezoelectricity is the mechanism by which certain crystalline structures generate electric potential when under strain, or, conversely, deform when subjected to an electric potential. It is this first effect that is important to this application. Though each MEMS device will generate a very small amount of power, a 1 m2 area can contain an array of millions of these devices. Energy harvesting, conservation, and efficiency are all key Department of Defense (DOD) priorities, and the universal application of these devices make them ideal for any expeditionary platform, such as ships, aircraft, and automobiles. This thesis designs and tests the first generations of acoustic and vibrational piezoelectric MEMS devices; including time-dependent finite element models, microfabrication processes, and the initial attempts at characterization and optimization.


In the period of Turkey's candidacy to the European Union (EU), many heated debates continue to take place which are related to welfare effects of being in a common market. In this thesis we analyzed a selected sample of the European Union Law cases about Single Market and Four Freedoms with an economic approach. We developed simple models of free movement of goods, free trade, and free movement of workers; we discussed the welfare effects of these movements for countries and for the entire Union. We also gave examples of reference cases, and discussed the effects of such decisions in the European Court of Justice. In addition, there is a special focus on intellectual property rights, the concept of patent, and its effects on free trade since they are important topics in Law and Economics literature from which many discussions arise. In addition, an overview of EU law making process and a historical background of the Single Market and economic integration of the EU is provided in this thesis. We also discussed some views about main stream economics in which trade liberalization and factors of production mobility is always assumed as improving welfare. We concluded stating that even free trade and free movement of workers are beneficial in theory; both are important topics for which well-established policy applications are required.


ABSTRACT Hypogean Molopina of Pyrenees with the description of a new species of Zariquieya Jeannel, 1924 from Spain (Coleoptera, Carabidae, Pterostichini). A second blind species of the genus Zariquieya Jeannel, 1924, Z. boumortensis n. sp., is described from the southern slope of central Spanish Pyrenees (Lleida, Spain). Morphological structure of the new species, especially male and female genitalia as well as the external morphology suggests that this carabid beetle should be included in the genus Zariquieya, created for a single species endemic of eastern Spanish Pyrenees. The new species is morphologically distinct from Z. troglodytes Jeannel, 1924 by numerous characters like maxillary palpus glabrous, pronotum more transverse, frontal impressions lighter, and elytra with flat disk without strong lateral and apical declivity. A key for identification of Pyrenean Molopina is given, and ecology and biogeographical considerations are detailed, including distribution map of Pyrenean hypogean Molopina.


We study stabilization of collective motion of N constant-speed, planar particles with less than all-to-all coupling. Our interest is in circular motions of the particles around the fixed center of mass of the group, as has been studied previously with all-to-all coupling. We focus on coupling defined by a ring, i.e., each particle communicates with exactly two other particles. The Kuramoto model of coupled oscillators, restricted to "ring" coupling, serves as our model for controlling the relative headings of the particles. Each phase oscillator represents the heading of a particle. We prove convergence to a set of solutions that correspond to symmetric patterns of the phases about the unit circle. The exponentially stable patterns are generalized regular polygons, determined by the sign of the coupling gain K.


Abstract Drought is one of the most significant extreme event facing the world, affecting the society and the environment. Located in SE Romania, Dobrogea Region is characterized by a temperate climate with strong continental influences, being affected by drought episodes which cause significant damages and economic costs over extensive agricultural areas. Risk reduction, continuous vegetation monitoring, and management implementation are facilitated by complementary use of vegetation indices and biophysical parameters derived from satellite products (gridded data) within-situ data (point data). The paper focuses on:i) evaluating the extent and intensity of drought in Dobrogea, Romania, based on Normalized Difference Drought Index (NDDI) and Fraction of Absorbed Photosynthetically Active Radiation (FAPAR); ii) fires analysis, based on the Thermal Anomalies/Fire locations product (MCD14DL); iii)the correlation between the fires with the NDDI; iv) and the correlation between fires with the Land Surface Temperature (LST) product. The vegetation indices, biophysical parameters and fires are computed from Moderate Resolution Imaging Spectroradiometer (MODIS) daily and eight days' synthesis products, during 22th of March - 29th of August 2000-2015. The results highlight the areas most affected by drought (moderate, severe and extreme) and fires in the Dobrogea.


Black women student-athlete activists at a historically white institution of higher education represent a group with unique lived experiences framed by intersecting identities. As student-activists, they are at risk for adverse mental health concerns associated with the emotional toils of fighting for racial justice. As Black female student-athletes at a historically white institution, they are also at risk for isolation. Acknowledging that race, class, and gender consistently intersect in sport is a necessary prerequisite for better mental health treatment, and for understanding Black women in sport and society. The purpose of this report is to identify the target groups' needs from their perspectives as Black women student-athlete activists, for the purposes of understanding and serving them better. We present interviews with six Black female student-athlete activists at a historically white institution of higher education and three recommendations for sport psychology consultants positioned to be their allies.


In 1884, the Supreme Court was presented with dichotomous views of photography. In one view, the photograph was an original, intellectual conception of the author-a fine art. In the other, it was the mere product of the soulless labor of the machine. Much was at stake in this dispute, including the booming market in photographs and the constitutional importance of the originality requirement in copyright law. This first confrontation between copyright law and technology provides invaluable insights into copyright law's ability to adapt and accommodate in the face of a challenge. An examination of these historical debates about photography across the domains of law, art, commerce and technology, the social sciences, and popular culture suggests that the particular contours of the author that continue to pose problems-particularly its predilection for creation over selection-can be located and attributed to this historical moment. The "author" took a particular shape in response to historically specific constraints, and the resulting doctrine has left a lasting impression on the way we read photography today.


The influences of various laser modes on the splitting beam effect of Dammann grating are studied in theory and by numerical simulation. The results show that fundamental mode laser resembles plane wave while high order mode laser differs from plane wave in the splitting beam effect by Dammann grating. Therefore, the fundamental mode laser is more suitable to be the light source to improve the energy efficiency in far-distance image detecting systems, such as laser image ladar, which use Dammann grating in the illumination system.


"Prophet from Plains" covers Nobel Peace Prize winner, Jimmy Carter's major achievements and setbacks in light of what has been at once his greatest asset and flaw: his stubborn, faith-driven integrity. Carter's remarkable postpresidency is still in the making; however, he has already redefined the role for all who follow him.Frye Gaillard, who wrote extensively about Carter at the Charlotte Observer, was among the first to take seriously the Carter postpresidency and to challenge many accepted conclusions about his term in office. Carter was not an irresolute president, says Gaillard, but rather one so certain of his own rectitude that he misjudged the importance of "selling" himself to America. Ranging across the highs and lows of the Carter presidency, Gaillard covers the energy crisis, the Iran hostage situation, the Camp David Accords, the Panama Canal and other treaties, and the new diplomatic emphasis on human rights. Carter stuck with his established priorities once out of office but was far more effective outside the strictures of presidential politics. Gaillard's coverage of this period includes Carter's friendship with Gerald R. Ford, his work through the Carter Center on disease control and election monitoring, and his association with Habitat for Humanity."Prophet from Plains" locates Carter in the tradition of the Old Testament prophets who took uncompromising stands for peace and justice. Resisting the role of an above-the-fray elder statesman, Carter has thrust himself into international controversies in ways that some find meddlesome and others heroic.


The administration of dicoumarol to four elderly diabetics who were daily receiving 500 mg. tolbutamide led to an increase in the tolbutamide concentration in the blood associated with a fall in blood sugar. The accumulation of tolbutamide was due to an increase in the half-life of tolbutamide in the blood from the normal average of 4.9 hours to an average of 17.5 hours. The mechanism responsible for this increase may be inhibition of tolbutamide metabolism in the liver by dicoumarol. This accumulation may well increase the risk of hypoglycemia, such as has been demonstrated after administration of sulfaphenazole to diabetic patients receiving tolbutamide. Phenindione does not seem to have a similar effect and, accordingly, would appear to be preferable in anticoagulant therapy in diabetics receiving tolbutamide.


In the present article we describe a new setup for an atomic force microscope in the beetle‐type geometry. The microscope consists of a compact head standing on three piezo legs with a fourth central piezo carrying the cantilever tip. We use the laser beam deflection method to detect the deflection of the cantilever. All optical components are integrated into the microscope head which has a diameter of 40 mm. This compactness results in a high mechanical stability, while the adjustment of the optical pathway is still easy to handle. The microscope can be used in UHV and in air. Measurements on KBr(100) in air show the capability of the microscope to obtain a resolution up to atomic corrugations.


In its (in)famous decision against Grokster and Streamcast the Supreme Court managed to sidestep the fundamental issues of copyright in the information age and focused on a generic bad faith standard and obscure business models instead. This short article provides an introduction to fundamental questions of indirect liability for copyright infringement under US law and follows the trail of decisions leading up to the confusing Supreme Court opinion (including Aimster and Napster). It analyzes the arguments made and briefly discusses possible implications for the interest groups involved. The paper concludes that file sharing is still a dubious, but not illegal business and that all important questions remain open even after the ruling. All parties involved can feel both worried and assured by the decision, but no one can claim a decisive victory (yet). The clear line between the Consumer Electronics (and Software) industry and the Entertainment business divides not only the state of California, but the Supreme Court bench as well.


Capalictus , a new subgenus of Lasioglossum Curtis, 1833 (Hymenoptera, Apoidea, Halic-tidae), endemic to the South African Cape Province, is described. The type species is Halictus mosselinus Cockerell, 1945. Evylaeus ( Sellalictus ) fynbosensis (Pauly et al. , 2008) is a new junior synonym of  L. ( C. ) mosselinum . Three new species are described: Lasioglossum ( Capalictus ) hantamense sp. nov., L. ( C. ) tigrinum sp. nov. and L. ( C. ) timmermanni sp. nov. DNA sequence data from three nuclear genes support morphologically-determined species limits. Capalictus is a basal clade of the Hemihalictus series of Lasioglossum .


There is a close link between climate change and water resources owing to the strong relationship between climate and hydrology. Effects of climate change on water availability have potential to impact water supply for domestic, agricultural, industrial, environmental, and hydro-electricity generation purposes in Turkey. Thereby, it is necessary to develop hydro-meteorological impact studies in Turkey to have better understanding of how climate change may affect the regions, in order to enable policy makers to produce efficient adaptation policies. The first step of a hydro-meteorological impact study is to make a comprehensive review of the literature to identify where and how to contribute. This paper aims to provide an extensive review of the literature on climate change effects on hydrometeorology and water resources in Turkey and it proposes to put a light on the future climate change studies in Turkey.


In this paper we propose a data acquisition methodology, and a Machine Learning solution for the partially automated evaluation of real estate properties. The novelty and importance of the approach lies in two aspects: (1) when compared to Automated Valuation Models (AVMs) as available to real estate operators, it is highly adaptive and non-parametric, and integrates diverse data sources; (2) when compared to Machine Learning literature that has addressed real estate applications, it is more directly linked to the actual business processes of appraisal companies: in this context prices that are advertised online are normally not the most relevant source of information, while an appraisal document must be proposed by an expert and approved by a validator, possibly with the help of technological tools. We describe a case study using a set of 7988 appraisal documents for residential properties in Turin, Italy. Open data were also used, including location, nearby points of interest, comparable property prices, and the Italian revenue service area code. The observed mean error as measured on an independent test set was around 21 K€, for an average property value of about 190 K€. The AVM described here can help the stakeholders in this process (experts, appraisal company) to provide a reference price to be used by the expert, to allow the appraisal company to validate their evaluations in a faster and cheaper way, to help the expert in listing a set of comparable properties, that need to be included in the appraisal document.


By Real-Time PCR technique, the existence of polymorphism at the level of PrP gene (associated with susceptibility to scrapie) has been revealed in Botosani Karakul sheep. Practically, the polymorphism was analyzed at codons 136, 154 and 171. Among the five alleles (ARR, ARQ, AHQ, ARH and VRQ) incriminated in association with this disease in ovine species, only three of them were found in the Botosani Karakul breed determining the phenotypic expression of all six possible genotypes. The most common allele is ARQ (56.10%); the incidence of allele ARR (38.21%) is considerable, and the allele ARH has a low prevalence (5.69%). The most frequent genotype is ARQ/ARQ (47.97%), followed by genotype ARR/ARR (26.83%); the genotypes ARR/ARQ (14.63%) and ARR/ARH (8.13%) record moderate or relatively low frequencies, the other two genotypes (ARO/ARH = 1.63% and ARH/ARH = 0.81%) being met rarely in the population. The distributions of genotypes at the PrP locus make the total homozygosity (75.61%) to be well represented compared to the total heterozygosity (24.39%). In the Botosani Karakul breed, major discrepancies were observed between the empirical frequencies and those estimated, so that we witness a very significant genetic disequilibrium Hardy-Weinberg at the PrP locus. In the Botosani Karakul sheep, the prion genotypes that are associated in the highest degree with scrapie are completely absent (classes of risk R4 and R5). Thus, all individuals are resistant to scrapie (50%) (classes of risk R1) or have a low risk of contracting the disease (50%) (class of risk R3). This association represents a notable selective advantage of Botosani Karakul sheep compared to all other autochthonous or foreign sheep breeds.


Detrital zircons from Devonian and Carboniferous synorogenic flysch deposits occurring in an imbricate stack have been dated by laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) to: (1) obtain a maximum depositional age to constrain the maximum age limit for thrusting of exotic terranes in the NW Iberian Massif; (2) correlate the zircon age populations with published ages in nearby units to establish their possible source areas. The maximum depositional ages are Late Devonian for rocks high in the structural nappe pile (Gimonde Formation), in accordance with palynomorph dating, and around the Devonian–Carboniferous boundary for structurally lower samples (San Vitero Formation). Used in conjunction with previously published ages, the new ages are interpreted in terms of the advance of the thrust system responsible for the emplacement of exotic terranes upon the Iberian autochthon during the Variscan collision. Early Variscan zircon population ages indicate the exotic terranes as the source of synorogenic sediments, whereas their scarcity suggests derivation from the Iberian autochthon. One of the samples analysed lacks Variscan detrital zircons; this feature, together with the absence of an Early Palaeozoic zircon age population, puts into question its synorogenic character and suggests that the sample may be representative of the preorogenic parautochthon.


Over 500 samples were collected from as wide a variety of vegetation types as possible. The principles of the Zurich Montpellier School of phytosociology were followed to form the data into a species-releve matrix for each vegetation type. The CLUSTAN package of computer programs was utilised, using Ward's Error Sum of Squares as a sorting routine, to produce differentiated data tables. 72 groups were identified, and described and compared with units recognised in Britain and North-West Europe. 38 groups were assigned to 21 Associations and the remainder were left as noda of doubtful status within alliances and orders. All communities were classified into higher syntaxa following, with only a few exceptions, the scheme of Westhoff and Den Held (1969). The Classes and Alliances used to contain the communities are as follows: Cakiletea maritimae atriplicion littoralis open communities (of mainly annual species) of shingle beaches and strandlines Agropyretea pungentis Honkenyo-Crambion maritimae Open, unstable, halonitrophile communities of biennials and perennisals and shingle beaches and strandlines Agropyrion pungentis Stable communities in maritime areas subject to disturbance. Ammophileta Agropyrion boreoatlanticum Unstable pioneer communties on sand. Ammophilion borealis Moile dune communities. Plantaginetea majoris Agropyro-Runicion crispi Disturbance communities of transitional and relatively unstable habitats. Phragmitetea Magnocaricion Large sedge communiies. Koeleric-Corynephoretea Galio-Koelerion Dry grasslands on acidic soils in the atlantic sector Festuco-Brometes Mesobromion erecti Semi-dry calcareous grasslands. Saginetea maritimae Saginion maritimae closed maritime grasslands on sandy soils in the upper saltmarsh regions. Asteretes tripolii Puccinellion maritimae Halophyte communities of lower saltmarshes. Elecharion uniglumis Communal sedge communities of saltmarsh boundaries. Puccinellio-Spergularion salines Disturbed maritime communities on sand and gravel Molinio-Arrhenatheretea Calthion Palustris Fen meadow vegetation.Cynosurion cristatti Communities of graged, lowland pastures and simliar habitats. Montio-Cardaminetea Cratoneurion Chalk and limestone spring communities. Parvocaricetea Caricion curto-nigrae Small sedge communities in habitats near springs. Caricion devallianae Small sedge vegetation of base-rich habitats. Scheuchzerietea Rhyncosporion albae Species poor vegetation in pools in poor fens and mires Caricion Lasiocarpae Communities of pools in moderatley rish fans and mires. Oxycocco-Sphagnetea Ericion tetralicis Wet heath communities on shallow peat. Erico-Sphagnion Bog Communities. Nardo-Callunetea Violion caninae rough grasslands. Ulicion Nanae Oceanic heaths. Caricetea curvula Arctostaphyleto-Centrarion nivalis Chionophobous montane grass and dwarf-shrub heath communities. The occurrence and interrelation ships of the plant communities of the Southern Isles are discussed, and the potential pressures on Shetland vegetation are examined.


Remote sensing of radiative indices must balance spatially and temporally coarse satellite measurements with finer-scale, but geographically limited, in-situ surface measurements. Instruments mounted upon an Unmanned Aerial Vehicle (UAV) can provide small-scale, mobile remote measurements that fill this resolution gap. Here we present and validate a novel method of obtaining albedo values using an unmodified quadcopter at a deciduous northern hardwood forest. We validate this method by comparing simultaneous albedo estimates by UAV and a fixed tower at the same site. We found that UAV provided stable albedo measurements across multiple flights, with results that were well within the range of tower-estimated albedo at similar forested sites. Our results indicate that in-situ albedo measurements (tower and UAV) capture more site-to-site variation in albedo than satellite measurements. Overall, we show that UAVs produce reliable, consistent albedo measurements that can capture crucial surface heterogeneity, clearly distinguishing between different land uses. Future application of this approach can provide detailed measurements of albedo and potentially other vegetation indices to enhance global research and modeling efforts.


As the world's political and economic leaders struggle with the aftermath of the Financial Debacle of 2008, this book asks the question: have financial crises presented opportunities to rebuild the financial system? Examining eight global financial crises since the late nineteenth century, this new historical study offers insights into how the financial landscape - banks, governance, regulation, international cooperation, and balance of power - has been (or failed to be) reshaped after a systemic shock. It includes careful consideration of the Great Depression of the 1930s, the only experience of comparable moment to the recession of the early twenty-first century, yet also marked in its differences. Taking into account not only the economic and business aspects of financial crises, but also their political and socio-cultural dimensions, the book highlights both their idiosyncrasies and common features, and assesses their impact in the broader context of long-term historical development. Available in OSO: http://www.oxfordscholarship.com/oso/public/content/management/9780199600861/toc.html


The gas phase thermal rearrangement of (cyclopropylidene)cyclopropane (bicyclopropylidene) was studied, and the pressure-independent Arrhenius parameters detd. as log(k/s-1) = (14.02+-0.33) - (39.2+-0.7) kcal.mol-1/RT.ln10, almost the same as those for (methylene)cyclopropane. Thus, the second cyclopropane ring in (cyclopropylidene)cyclopropane exerts virtually no influence on the kinetics of the thermal rearrangement of one of its methylenecyclopropane subunits. The rearrangement of (cyclopropylidene)cyclopropane to methylenespiropentane was found to be reversible, with an equil. compn. at 230 DegC of 1:166. These findings are discussed and accounted for. When heated to 350 DegC in a flow system, (cyclopropylidene)cyclopropane undergoes a clean rearrangement to methylenespirocyclopentane [90% yield, >=95% purity on a preparative scale (17.4 g)]. [2-(2-Propenyl)cyclopropylidene]cyclopropane, (2-ethenylcyclopropylidene)cyclopropane, and (E)-(2-methoxycarbonylethenyl)bicyclopropylidene were prepd. from (cyclopropylidene)cyclopropane in 50, 45, and 69% overall yields, resp. The thermal rearrangements of [2-(2-propenyl)cyclopropylidene]cyclopropane and (E)-(2-methoxycarbonylethenyl)bicyclopropylidene proceeded smoothly at 150-160 DegC, resulting in the formation of 4-methylenespiro[2.4]hept-5-ene and its deriv. in 79 and 50% isolated yields, resp., as the sole products, while the rearrangement of [2-(2-propenyl)cyclopropylidene]cyclopropane required higher temps. (200 DegC) and resulted in a complex mixt. of isomeric substituted methylenespiropentanes. Under flash vacuum pyrolysis conditions at 550 DegC, 4-methylenespiro[2.4]hept-5-ene initially formed from (2-ethenylcyclopropylidene)cyclopropane via 1-ethenyl-2-methylenespiro[2.2.]pentane, underwent a further vinylcyclopropane-to-cyclopentene rearrangement to yield a 1:1 mixt. of isomeric tetrahydropentalenes, i.e., 1,2,3,4-tetrahydropentalene and 1,2,3,5-tetrahydropentalene. This constitutes a novel and easy access to the tetrahydropentalene skeleton.


It is believed that the bICP0 protein encoded by bovine herpesvirus 1 (BoHV-1) stimulates productive infection by activating viral gene expression. Like the other ICP0-like proteins encoded by alphaherpesvirinae subfamily members, bICP0 contains a zinc RING finger near its amino terminus. The zinc RING finger of bICP0 activates viral transcription, stimulates productive infection, and is toxic to certain cell types. Apart from the zinc RING finger, bICP0 possesses little similarity to the herpes simplex virus type 1 ICP0 protein making it difficult to predict what regions of bICP0 are important. To begin to identify bICP0 functional domains that are not part of the zinc RING finger, a panel of transposon insertion mutants that span bICP0 was developed. A large domain spanning aa 78-256, and a separate domain that is at or near aa 457 was necessary for efficient transactivation of a simple promoter. Transposon insertion at aa 91 impaired bICP0 protein stability in transfected cells. Insertion of transposons into the acidic domain of bICP0 had little or no effect on transactivation of a simple promoter or protein expression suggesting this region does not play a major role in activating gene expression. Sequences near the C terminus (aa 607-676) contain a functional nuclear localization signal. Collectively, these studies indicated that bICP0 contains several important functional domains: (i) the zinc RING finger, (ii) two separate domains that activate transcription, and (iii) a C-terminal nuclear localization signal that is also necessary for efficient transactivation.


The Copyright Act of 1976 is far too long, complex, and largely incomprehensible to non-copyright professionals. It is also the work product of pre-computer technology era. This law also lacks normative heft. That is, it does not embody a clear vision about what its normative purposes are. This article offers the author's preliminary thoughts about why copyright reform is needed, why it will be difficult to undertake, and why notwithstanding these difficulties, it may nonetheless be worth doing. It offers suggestions about how one might go about trimming the statute to a more managemable length, articulating more simply its core normative purposes, and spinning certain situation-specific provisions off into a rulemaking process. Thirty years after enactment of the '76 Act, with the benefit of considerable experience with computer and other advanced technologies and the rise of amateur creators, it may finally be possible to think through in a more comprehensive way how to adapt copyright to digital networked environments as well as how to maintain its integrity as to existing industry products and services that do not exist outside of the digital realm.


BACKGROUND
The influence of testosterone on risk for cardiovascular events in men is uncertain. Previous observational studies of sex hormones and incident cardiovascular disease in men have reported inconsistent findings, limited by cohort sizes and different selection criteria.

OBJECTIVE
To analyze associations of serum total testosterone and sex hormone-binding globulin (SHBG) with incident cardiovascular events in men.

DESIGN
Cohort study.

SETTING
UK Biobank prospective cohort.

PARTICIPANTS
Community-dwelling men aged 40 to 69 years.

MEASUREMENTS
Testosterone and SHBG were assayed, and free testosterone was calculated. Cox proportional hazards regression was done, with outcomes of incident myocardial infarction (MI), hemorrhagic stroke (HS), ischemic stroke (IS), heart failure (HF), and major adverse cardiovascular events (MACE), adjusted for sociodemographic, lifestyle, and medical factors.

RESULTS
Of 210 700 men followed for 9 years, 8790 (4.2%) had an incident cardiovascular event. After adjustment for key variables, lower total testosterone concentrations (quintile 1 vs. quintile 5) were not associated with incident MI (fully adjusted hazard ratio [HR], 0.89 [95% CI, 0.80 to 1.00]), HS (HR, 0.94 [CI, 0.70 to 1.26]), IS (HR, 0.95 [CI, 0.82 to 1.10]), HF (HR, 1.15 [CI, 0.91 to 1.45]), or MACE (HR, 0.92 [CI, 0.84 to 1.00]). Men with lower calculated free testosterone values had a lower incidence of MACE (HR, 0.90 [CI, 0.84 to 0.97]). Lower SHBG concentrations were associated with higher incidence of MI (HR, 1.23 [CI, 1.09 to 1.38]) and lower incidence of IS (HR, 0.79 [CI, 0.67 to 0.94]) and HF (HR, 0.69 [CI, 0.54 to 0.89]), but not with HS (HR, 0.81 [CI, 0.57 to 1.14]) or MACE (HR, 1.01 [CI, 0.92 to 1.11]).

LIMITATION
Observational study; single baseline measurement of testosterone and SHBG.

CONCLUSION
Men with lower total testosterone concentrations were not at increased risk for MI, stroke, HF, or MACE. Calculated free testosterone may be associated with risk for MACE. Men with lower SHBG concentrations have higher risk for MI but lower risk for IS and HF, with causality to be determined.

PRIMARY FUNDING SOURCE
Western Australian Health Translation Network, Medical Research Future Fund, and Lawley Pharmaceuticals.


Abstract The purpose of this paper is to study the taphonomy of fossil flies (Diptera) preserved in the lacustrine deposits of the Florissant Fossil Beds (late Eocene), Colorado, United States. Three hundred and twenty-six fossil Diptera were examined, collected from a nearshore (n = 215) and an offshore (n = 111) site. The degree to which a specimen's preservation quality correlated with the ability to identify the specimen to various taxonomic levels and whether specimen size, orientation, or disarticulation had an effect on a preservation quality were evaluated. Also examined was the influence of depositional environment on these variables. Preservation quality was found to be important for identification to species level, but specimens of low preservation quality were still identifiable to the family and genus levels. Specimen size, orientation, and disarticulation were not correlated with the identifiability of a specimen. There was no significant difference in the orientation, disarticulation, or preservation quality of specimens found in the nearshore and offshore sites. There was a significant difference in the size of specimens preserved at each site, with larger specimens being found offshore. More specimens were found in the offshore site, but species richness did not differ between the two sites. Composition of taxa did differ depending on the site. These results demonstrate the importance of collecting all specimens, as even poor quality and disarticulated specimens are identifiable and useful in studies of insect ecology and evolution. In addition, depositional environments should be documented, as size sorting can bias the taxonomic composition of assemblages.


Context: Bupivacaine is commonly used agent for wound infiltration because of its local anesthetic effect. However, pethidine an opioid has both local anesthetic and systemic analgesic effect. The combined analgesic effect of pethidine may be superior to bupivacaine that has only a local anesthetic effect. Few studies have however supported the superiority of pethidine over bupivacaine for wound infiltration. Aims: The aim of this study is to evaluate the analgesic effect of pethidine in comparison with bupivacaine wound infiltration for postoperative pain control in nonparturients scheduled for myomectomy under spinal anesthesia. Setting and Design: This study is a prospective, randomized, double-blinded control trial of the analgesic efficacy of plain bupivacaine versus pethidine for patients scheduled for myomectomy under spinal anesthesia in a Tertiary Healthcare center in Nigeria. Subjects and Methods: Seventy-six American Society of Anesthesiologists 1 and 11 patients billed for myomectomy using spinal anesthesia were randomized into two groups. Group bupivacaine had wound infiltration with 50 mg isobaric bupivacaine at a concentration of 0.25%. Group pethidine had 1 mg/kg pethidine. In the ward, pain was assessed at various intervals at rest and on coughing using the numerical rating scale (NRS) pain assessment tool and the time of the first analgesic request. Statistical Analysis: NRS scores were presented as median with interquartile range, Continuous variables such as duration of analgesia and total analgesic consumption were analyzed using the unpaired Student's t-test. Results: The pethidine group had a longer time to first analgesic request, lower pain scores and a higher level of satisfaction. Conclusion: This study showed that postincision wound infiltration with pethidine at 1 mg/kg as a component in multimodal analgesia is more effective than 0.25% bupivacaine in the management of postmyomectomy pain.


Even with modern graphics hardware, it is still not possible to achieve high fidelity global illumination renderings of complex scenes in real time. However, as these images are produced for human observers, we may exploit the fact that not everything is perceived when viewing the scene with our eyes. We are drawn to certain salient areas of an image. Taking this into account, it is possible to selectively render parts of an image at high quality and the rest of the scene at lower quality without the user being aware of this difference. Methods exist for calculating which parts of an image are perceptually important, but generally they rely on having a fully rendered image to process. It is thus only possible to prioritise pixels to speed up the rendering of a frame once that frame has been rendered: an obvious catch. In pre-scripted animated sequences it is indeed possible to use rendered key frames to extract the necessary information, however, the cost of rendering such key frames could be significant and this is not appropriate for any interactive application. This paper presents a high speed OpenGL generated "Snapshot" of a frame to generate a saliency map to efficiently drive the selective global illumination rendering of an animated sequence.


Five cases are described that involve severe attacks on humans by dogs who were being trained or maintained on an electronic pet containment system. The system is designed to boundary train a dog through the use of electric shock in an escape-avoidance conditioning paradigm. Data were collected from legal documents filed in personal injury lawsuits. Analysis of the findings show that all dogs lacked a marked history of aggressive responding, all were adult males, and most were reproductively intact. All attacks happened near the boundary of the property. In every case, the system was operational at the time of attack. Moreover, in most cases, the dog received shock. Findings lend themselves to possible interpretation in terms of unconditioned aggression as a result of a dog having received electronic shock and avoidance-motivated aggression mediated through fear reduction toward human stimuli.


In the High Plains region of Texas it is not unusual for cotton (Gossypium hirsutum L.) to suffer pre-bloom fruit loss from insect injury or abiotic factors. The objective of this study was to investigate cotton's ability to compensate pre-bloom square loss and determine the impact this loss had on yield and fiber quality. Experiments were conducted in Lubbock, TX in 2009, 2010, and 2011 evaluating the impact of 0 to 100% pre-bloom square removal on cotton yield and fiber quality. During 2009 and 2010, cotton was able to either compensate up to 100% pre-bloom fruit loss, or suffered environmentally induced square loss resulting in limited boll carrying capacity that equalized yields and boll density across square removal treatments. If compensation was the reason for the lack of differences among treatments, the plants appear to compensate by producing more secondary or tertiary position fruit, as well as retaining additional mid- to upper-canopy fruit. However, evidence suggested that fiber quality may decline in some compensated bolls due to maturity issues. When environmental conditions were harsh, as in 2011, the cotton plant did not appear to be able to compensate fully for yield due to some pre-bloom fruit loss. This was most evident when an early-season termination event, such as a freeze, was simulated. Where cotton was allowed to mature fully, overcompensation was evident in 2011, with the greatest yields occurring at approximately 27% pre-bloom square removal. As with previous years, fiber quality in 2011 might be impacted adversely from compensated fruit.


Abstract A method applied previously to Plasmodium falciparum was applied to P. vivax to study the maturation of asexual erythrocytic forms of P. vivax in vitro and the effects exerted by chloroquine upon such maturation. Detailed studies were carried out in an effort to translate morphological observations into quantitative data and to identify particular morphological features that might be useful as indices of maturation and inhibition. With this experimental system, 1) asexual erythrocytic forms of P. vivax underwent maturation in vitro; 2) chloroquine added in vitro inhibited this maturation; 3) findings after incubation depended in substantial part upon the maturity of the asexual parasites present at the outset of incubation; 4) no single morphological feature or endpoint served as a consistently satisfactory indicator of maturation and inhibition; and 5) relationships between concentrations and effects of chloroquine were at times inconsistent or erratic, particularly when the asexual parasites present at the outset of incubation consisted mainly of late ameboid forms rather than early ameboid forms or ring forms. Although this experimental system may be of value as a means for assessing the effects of chloroquine upon P. vivax in vitro under some circumstances, it appears that—in terms of simplicity of quantitative assessment and interpretation, reliability, and validity—this system may be considerably less useful or satisfactory when appled to P. vivax than when applied to P. falciparum from man.


I will explore how evolution impacts the Christian notion of The Fall of man, and, ultimately, the atonement. Various theories of atonement in the Christian tradition generally assume universal and individual sinfulness in humanity. In some cases, this sinfulness is thought to be the result of a distinct moment of rebellion against God, and is transmitted to all of the descendants of Adam. Here, atonement involves Christ's sacrifice as the means liberate humanity from the bondage of our sinful nature. Evolution collides with these traditional models. Instead of a creation originally void of death and later corrupted by sin, evolution suggests that the very development of all life is attributed to a process driven by death and struggle for survival. By contradicting traditional views of The Fall, evolution has a secondary effect on the nature of the atonement: by asserting that humans are derived from previous species, rather than an individual special creation, evolution casts a shadow on the traditional mechanism used to explain how humanity became morally aware and responsible and calls into question what is meant by being created in the image and likeness of God. Despite these apparent contradictions, many have proposed models that attempt to reconcile evolution and theology. This paper will explore several of these proposals and will end by asserting that humans possess a unique, God-given capacity to discern morality, and therefore have a unique need for the atoning work of Christ.


Mitochondria are multifunctional organelles and their continued maintenance is required for cell homeostasis and function. Upon organelle dysfunction, a mitochondrial-to-nucleus communication, known as retrograde signalling, triggers an orchestrated expression of nuclear genes to relieve the stress and/or compensate the defect. The importance of the good working of these stress response pathways can be highlighted by the various pathophysiological developments associated with their impairment. The activation of two stress responsive pathways, known as the mitochondrial unfolded protein response (mtUPR) and the integrated stress response (ISR), was assessed upon various stresses such as the inhibition of the mitochondrial DNA (mtDNA) expression. While there is no induction of mtUPR-related gene markers HSPD1 (heat shock 60kDa protein 1) and ClpP (caseinolytic mitochondrial matrix peptidase proteolytic subunit), the transcription factor CHOP-10 (C/EBP homologous protein-10) was systematically overexpressed when mtDNA expression is inhibited. Furthermore, increased expression of this transcription factor correlates with induction of three genes associated with ISR activation: HERP (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1), ATF3 (activating transcription factor 3) and Trib3 (tribbles pseudokinase 3). These results were confirmed in three cancer cell lines (HeLa, Hep3B, MCF-7) as well as in primary human hepatocytes. In addition, the requirement of the ISR key transcription factor ATF4 (activating transcription factor 4) for CHOP-10 induction was demonstrated as well as the involvement of the GCN2 (General control non-derepressible kinase 2) kinase in the phosphorylation of eIF2α. Altogether, these data demonstrate that a GCN2-eIF2α-ATF4-CHOP-10 axis is activated in response to mitochondrial dysfunction. The decrease in cytosolic translation that occurs consequently to eIF2α phosphorylation could help to reduce the mitochondrial stress.


The separation of rare-earth elements (REEs) is usually carried out by a multi-stage solvent extraction process utilising organophosphorus extractants. Inspired by the structure of the solvating extractant tri-n-butyl phosphate (TBP), new sorbents were designed by covalently attaching short n-alkyl chains (ethyl, n-propyl and n-butyl) to titanium(IV) phosphate functionalised mesoporous MCM-41 silica by a layer-by-layer grafting route. Mesoporous MCM-41 silica served as a versatile porous support and the grafted titanium(IV) derivatives provided enhanced acid stability and solvating extraction capability. Various characterisation methods including solid-state 13C, 29Si and 31P magic-angle spinning (MAS) nuclear magnetic resonance (NMR) and simultaneous thermogravimetry and differential scanning calorimetry-mass spectroscopy (TG/DSC-MS) were used to confirm the ligand attachment. The hybrid materials showed a better uptake of rare-earth ions from nitrate feed solution than the unmodified inorganic material. The optimal separation factor (SF) obtained for scandium–lanthanum separation is in excess of 100 000 at pH 2.1. The SFs calculated for dysprosium–neodymium are approximately 3, which is comparable to that of TBP in a typical solvent extraction setup. This study provides a new strategy to design inorganic–organic hybrid sorbents based on the structure of organophosphorus extractants via metal(IV)–O–P bonds.


The Child Justice Act 75 of 2008 was published in GG 32225 of 11 May 2009. The Act is discussed in the chapter on Criminal Law. For purposes of the Law of Persons it should be noted that the Act raises the minimum age of criminal accountability from seven to ten years (s 7(1) and (3)). A child between ten and fourteen years of age is presumed to be criminally unaccountable (s 7(2) and (3)). Such a child has criminal capacity only if the state proves beyond reasonable doubt that when the alleged crime was committed, the child had the capacity to understand the difference between right and wrong and to act in accordance with that understanding (s 11(1)).


Functional relationships between objects, called 'attributes', are of considerable importance in knowledge representation languages, including Description Logics (DLs). A study of the literature indicates that papers have made, often implicity, different assumptions about the nature of attributes: whether they are always required to have a value, or whether they can be partial functions. The work presented here is the first explicit study of this difference for (sub-)classes of the CLASSIC DL, involving the same-as concept constructor. It is shown that although determining subsumption between concept descriptions has the same complexity (though requiring different algorithms), the story is different in the case of determining the least common subsumer (lcs). For attributes interpreted as partial functions, the lcs exists and can be computed relatively easily; even in this case our results correct and extend three previous papers about the lcs of DLs. In the case where attributes must have a value, the lcs may not exist, and even if it exists it may be of exponential size. Interestingly, it is possible to decide in polynomial time if the lcs exists.


Sexual Assault in Canada is the first English-language book in almost two decades to assess the state of sexual assault law and legal practice in Canada. Gathering together feminist scholars, lawyers, activists and policy-makers, it presents a picture of the difficult issues that Canadian women face when reporting and prosecuting sexual violence. The volume addresses many themes including the systematic undermining of women who have been sexually assaulted, the experiences of marginalized women, and the role of women's activism. It explores sexual assault in various contexts, including professional sports, the doctor–patient relationship, and residential schools. And it highlights the influence of certain players in the reporting and litigation of sexual violence, including health care providers, social workers, police, lawyers and judges. Sexual Assault in Canada provides both a multi-faceted assessment of the progress of feminist reforms to Canadian sexual assault law and practice, and articulates a myriad of new ideas, proposed changes to law, and inspired activist strategies. This book was created to celebrate the tenth anniversary of Jane Doe's remarkable legal victory against the Toronto police for sex discrimination in the policing of rape and for negligence in failing to warn her of a serial rapist. The case made legal history and motivated a new generation of feminist activists. This book honours her pioneering work by reflecting on how law, legal practice and activism have evolved over the past decade and where feminist research and reform should lead in the years to come.The PDF file does not include the full text.


Can Google Trends data be used to proxy socially sensitive sentiments, and can such proxies explain election outcomes? This thesis analyzes the effects of different social sentiments, proxied by Google search data, on outcomes for the Republican Party in the 2008, 2012 and 2016 U.S. presidential elections. We assess the relationship between three socially sensitive sentiments and the outcome of presidential elections. The sentiments we examine are racial animus, immigration skepticism and far-right sentiment. We use data on the search terms "nigger" or "niggers", "Breitbart News", "Stormfront" and "Drudge Report", and "Illegal immigration and residence" ahead of the three latest U.S. presidential elections to assess the prevalence of these sentiments. We look at the sentiments in both a long-term context, over a year, and short-term context, over two weeks. Using a fixed effects model controlling for both state and time fixed effects, we find a positive effect of long-term immigration skepticism, and both long-term and short-term farright sentiment, on the Republican election outcome. The estimated effects are small in magnitude. However, in the context of presidential elections, where a change of 1 percentage point can alter the election outcome, even small effects have potentially large consequences. Thus, our findings should be of value to both opinion pollsters and campaign strategists. Also, our analysis shows that higher increases than 1 index point in the proxied social sentiments should be regarded when interpreting the estimated effects, suggesting that the actual effect on the election outcome is likely larger in magnitude. The findings presented are especially interesting in two regards. Firstly, they contribute to the existing literature on the use of Internet search data in predicting and explaining election outcomes, as well as the literature on determinants of voting. Secondly, they bolster the argument for consideration of web search data in future election predictions and analyses. Further, the size, variation and availability of search data increases constantly due to continuing and substantial growth in online searches.


Digital Image Processing plays a vital role in several applications. One of the applications is detection of people faces in a digital photo. Several research works have been progressing in the field of face identification and matching, facial expressions identification, smile detection, etc. Any application related to face, first step is detection of face. Thus, the face detection plays a key role. The face detection is a complicated process due to background objects, orientation, scale, lighting, geometrics, quality of image, occlusion, disguise etc. This paper discusses different research techniques published in the peer reviewed journal and proposed a technique to detect faces in a group photo. General Terms Image Processing.


This thesis is an examination of five Anglican home-missionary organisations which operated in the Diocese of London in the latter half of the nineteenth century. These five organisations were all entirely dependant upon the financial support of the Anglican laity to provide their revenue. The main thrust of the thesis is an analysis of the finances of these home-missionary organisations. The initial four questions that this thesis examines are: how did the organisations raise money; who did they solicit support from; to what extent were the societies successful in soliciting financial support to carry out their aims; and did the funding revenue streams remain stable through the period? This is with the main purpose of evaluating the Anglican community's support of these organisations during the period of study, in terms of who gave financial support and how this changed. Drawing on the wealth of material contained in the annual reports of the organisations chosen for this study, this thesis provides a comprehensive analysis of the subscriptions and donations and in doing so identifies an important shift in the gender-base of the laity's support at the end of the period. In seeking to explain the loss of the male funder in the late nineteenth century, the thesis engages with the key wider themes of philanthropy and secularisation. The assumption of this thesis is that modern religious bodies have to function as economic agents, that they need steady sources of income, and have to have mechanisms to raise sufficient funds on an annual basis. It argues that the decline in financial support from the Anglican laity within the period was not a result of failing fundraising techniques of the organisations themselves. Instead, it was a symptom of a wider malaise. The thesis explores the ethos of giving in the latter half of the nineteenth century and argues that an important factor in the decline of giving was the waning of the teaching of the doctrine of Christian stewardship after its mid-century renaissance. It argues that the new generation of Christians born in the latter half of the nineteenth century did not have the same ethos of giving that their parents had held. In doing so, it concludes that this shift was a significant change in the 'consequential dimension' of religion, which is how people behave as a consequence of their faith.


Background: Awareness of observed and expected incidence of cancers is so important in managing cancer as the third mortality cause in Iran. In the present study, we evaluated observed and the expected incidence of common cancers in Chaharmahal and Bakhtiari province. Materials and Methods: This study is a Secondary data analysis. All data about pathology-based cancer registration (Cancer diagnosis was based on pathological laboratory, ICD-O2) in Chaharmahal and Bakhtiari in Southwestern Iran in 2010–2014 was used. By dividing the number of registered cases of each cancer in every age group into the total observed cancers in that age group, the observed ratio of each cancer in that age group was calculated. Then, using the proposed coefficients Parkin and age-standardized cancer ratio method, the expected ratios in each age group, were calculated. Results: In 5 years study, 2918 new cases of cancer were recorded. Out of them, 1735 (59.46%) were male. The annual average total occurrence of all cancers in this province was 68.2/100,000 populations. The observed incidence ratios of common cancers, including stomach, breast, colorectal, thyroid, lymph nodes, ovaries, gall bladder, the bladder and the brain, were 0.11, 0.12, 0.09, 0.06, 0.02, 0.03, 0.01, 0.08, and 0.05, respectively. The expected incidence ratios of above-mentioned cancers are 0.11, 0.13, 0.1, 0.06, 0.02, 0.03, 0.01, 0.08, and 0.05, respectively. Based on observed (O) and expected (E) comparison, breast and colorectal cancer had higher incidence than expected ratio. Conclusion: Our results showed that in our area, treatment programs and health plans should focus on cancer registration, especially on common cancers and reevaluate breast and colorectal cancer occurrence. Therefore, the plan for the control and prevention of this cancer must be a high priority for health policymakers.


I grew up eating pineapples in everything; well, nearly everything (let's not exaggerate). They were a sweetener, made things juicy. Pineapple jam, pineapple breadcrumbs stuffed in the chicken roast for Sunday lunch after church, pineapple on the barbeque for the Christian folk my parents (MotherJoy and Onward) invited home, crushed pineapple in the punch, pineapple in the boiled fruitcake, pineapple in sandwiches as a treat through the summer holidays, pineapple in the curried rice salad for days my mother felt adventurous. We ate from pineapples too. Imagine then refined white sugar being spooned out of a fancy pineapple canister with its spiky pineapple top of a lid. Milk pouring out of a matching pineapple jug, part of a set. Salad out of large wooden bowls in the shape of half pineapples. And we ate off flat yellow pineapple dinner plates, helped ourselves to butter cake and sponge rolls on Sundays for tea off glass pineapple platters. People thought us quirky, we laughed them off. In the Solider family, this attachment to the fruit of the land was our way of stitching ourselves in place, saying we belonged. And in sub-tropical Queensland, the pointy state of Australia, what a surfeit.


This paper presents a new learning paradigm that consists of a Hebbian and anti-Hebbian learning. A layer of radial basis functions is adapted in an unsupervised fashion by minimizing a two-element cost function. The first element maximizes the output of each gaussian neuron and it can be seen as an implementation of the traditional Hebbian learning law. The second element of the cost function reinforces the competitive learning by penalizing the correlation between the nodes. Consequently, the second term has an anti-Hebbian effect that is learned by the gaussian neurons without the implementation of lateral inhibition synapses. Therefore, the decorrelated Hebbian learning (DHL) performs clustering in the input space avoiding the nonbiological winner-take-all rule. In addition to the standard clustering problem, this paper also presents an application of the DHL in function approximation. A scaled piece-wise linear approximation of a function is obtained in the supervised fashion within the local regions of its domain determined by the DHL. For comparison, a standard single hidden-layer gaussian network is optimized with the initial centers corresponding to the DHL. The efficiency of the algorithm is demonstrated on the chaotic Mackey-Glass time series.


In spite of the vast amount of evidence on the benefits of blood pressure (BP) lowering that has accumulated to date, hypertension (HTN) remains the leading risk factor for disease and disability worldwide. Since the first BP-lowering agents became available in the 1950s, their effects have been tested thoroughly by means of the best evidence-providing approach, namely, large randomised controlled trials (RCTs). In the same way, the pharmacogenomics of HTN have the potential to identify genetic biomarkers that predict the response of BP-lowering agents through genome-wide association studies (GWAS), which analyse quantitative traits at millions of markers across the genome to identify genetic variations that could contribute to HTN. For the most part, computational approaches and software tools have played a significant role in translating RCTs and GWAS findings.

This thesis aims first to systematically review the BP responses of main BPlowering
agents, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics (DIs) and beta-blockers (BBs) in RCTs, and second to identify the single nucleotide polymorphisms (SNPs) associated with the BP-lowering responses of CCBs and BBs on Nordic Diltiazem (NORDIL) subjects using GWAS.

Description of the research results: Following the Population Intervention Comparison Outcome Study (PICOS) design framework, a literature search of multiple sources resulted in the identification of 10,577 publications, with 5,568 unique records identified after duplicates were excluded. In total, 184 studies were identified as potentially eligible, of which 82 RCTs with a total of 197,684 participants were selected for quantitative synthesis. With regard to BP-lowering strategies, 13 studies with 41,886 participants focused on lowering BP
intentionally, while the remaining 69 studies (155,798 participants) were classified as unintentional BP-lowering studies.

Risk of bias in included studies: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, all included studies were described as RCTs; however, most studies did not address how treatment randomization occurred or how allocation of treatment was concealed. All included studies also stated that they were double-blind studies, but again, most did not describe how the double blinding was ensured throughout the studies. The risk of attrition bias was avoided as all randomized participants were included in the analysis. All of the studies had a low risk for reporting bias. BP-lowering agents were added to randomly allocated treatment to control high BP; consequently,
one potentially unclear source of bias was present in 13 of the 82 studies. The overall quality was rated to be acceptable to high. In all, 48 studies were rated to be high-quality studies, and 34 studies were rated as acceptable quality.

Effect of intervention: After a systematic search and selection process, 56 studies were included in the analysis of delta BP response, 37 studies were included in the analysis of single-measure BP response and 20 studies were included in the analysis of repeated measures. A number of BP-lowering agents showed a significantly (P<0.05) superior BP response in comparison with other agents included in the review; however, the level of BP response was still small. CCBs were superior to ACEIs in lowering both systolic BP (SBP) and diastolic BP (DBP). DIs were superior to ACEIs and CCBs in lowering SBP. ARBs were superior to BBs in lowering SBP. CCBs and DIs were significantly superior to placebos in lowering both
SBP and DBP.

Genome-wide study: Following NORDIL quality control standards, a final set of 3,850 samples and 500,905 SNPs was available for analysis. In total, 51 SNPs showed a significant (P<1X10-5) association with BP response. The top discordant signals identified in NORDIL included five SNPs for SBP on BB arm, seven SNPs for DBP on BB arm, 12 SNPs for SBP on CCB arm and nine SNPs for DBP on CCB arm. Discordant SNPs from the NORDIL were replicated, based on the interests of five collaborative RCTs; including 11 SNPs for SBP on BB arm, 22 SNPs for DBP on BB arm, 23 SNPs for SBP on CCB arm and 18 SNPs for DBP on CCB arm. However, no SNP achieved a genome-wide significance of (P<5x10-8).

Future recommendations: Further systematic reviews of RCTs comparing different BP-lowering agents are required to provide evidence of the options for BP-lowering medication. Specifically, there is a need to study BP response as an outcome by itself, taking into account different BP-lowering agent combinations,including classes and sub-classes, along with co-morbidities such as type 2 diabetes mellitus, coronary heart disease and chronic renal failure.
Regarding the genome-wide study, further studies are needed to clarify the potential contribution of plausible SNPs in relation to CCB and BB response in HTN. These studies should include comprehensive sequencing of the candidate interval, genotyping of variants in many population samples, testing for association, functional studies and investigation of interactions with other genes or environmental factors. Furthermore, genome-wide studies need to identify directionally discordant signals between SNP and BP response for BB and CCB and confirm the validity of a SNP BP response by analysing the SNP effect on mortality.


In the Edwardian era, Manchester was the workshop of the world and its leading football club, Manchester United, was one of the best in the land. Unfortunately, its stadium at Bank Street did not reflect its aspirations. So the directors took the brave decision to build a spectacular new stadium to reflect the club's, and the city's, status. On 19 February 1910, Old Trafford was open for action. Ian Marshall tells the astonishing story of the hundred years that followed. From early triumph, through inter-war depression, Old Trafford saw it all. But when the ground was twice bombed during the Second World War, its entire future was in question. However, under the inspirational managership of Matt Busby, both the team and the ground were rebuilt, and a new era of dominance was ushered in in the 1950s, only for United to be once again struck down by Munich. Speaking to players, employees and fans from across the years, as well as original research into the United archives, Marshall explains how Old Trafford has remained central not just to United but to the fortunes of an entire city. Old Trafford is the definitive story of an iconic venue.


This study examines firm performance surrounding insiders' prepaid variable forward (PVF) transactions to infer insiders' information when they enter these off-market contracts. PVFs allow insiders to hedge downside risk, share performance gains, and obtain immediate large-sum cash payments for investment or consumption. On average, PVF transactions cover 30% of a sample insider's firm-specific wealth ($22 million), which is substantially larger than a typical open-market sale. PVFs systematically follow strong firm performance and precede degraded stock and earnings performance. PVFs also precede periods of negative abnormal returns relative to potential alternative investments. The documented association between PVFs and performance declines does not appear to result from the market's response to transaction disclosure, participant self-selection, or general price reversals. Thus, evidence suggests that insiders use PVFs to diversify firm-specific holdings in anticipation of performance declines.


Introduction: The nucleus cuneiformis (NCF) and ventrolateral periaqueductal gray (vlPAG), two adjacent areas, mediate the central pain modulation and project to the nucleus raphe magnus (NRM). Methods: This study examined whether the antinociceptive effect of morphine microinjected into the NCF is influenced by inactivation of vlPAG and NRM in rats. Animals were bilaterally microinjected with morphine (2.5 μg/0.3 μl saline) into the NCF. Electrolytic lesions were made in vlPAG (0.1 mA, 45 sec) and/or NRM (1 mA, 30 sec). Tail-flick latency (TFL) was measured at 30, 60, 90 and 120 min after microinjection. Results: The results showed that TFLs are significantly decreased in vlPAG+NRM lesions group at 30 (P < 0.001) and 60 (P < 0.01) min after intra- NCF administration of morphine whereas TFLs did not affect in solely vlPAG lesion animals. Our findings show that concurrent lesions of NRM and vlPAG completely reversed the analgesic effect of morphine in NCF. However, vlPAG do not play a critical role directly in pain modulatory system elicited from NCF, at least at the level of morphine-induced analgesia. Discussion: It can be concluded that its interactive effect in descending pain modulation from NCF to NRM should not be neglected.


Detection of visually salient image regions is useful for applications like object segmentation, adaptive compression, and object recognition. Recently, full-resolution salient maps that retain well-defined boundaries have attracted attention. In these maps, boundaries are preserved by retaining substantially more frequency content from the original image than older techniques. However, if the salient regions comprise more than half the pixels of the image, or if the background is complex, the background gets highlighted instead of the salient object. In this paper, we introduce a method for salient region detection that retains the advantages of such saliency maps while overcoming their shortcomings. Our method exploits features of color and luminance, is simple to implement and is computationally efficient. We compare our algorithm to six state-of-the-art salient region detection methods using publicly available ground truth. Our method outperforms the six algorithms by achieving both higher precision and better recall. We also show application of our saliency maps in an automatic salient object segmentation scheme using graph-cuts.


Osteoarthritis is the most common degenerative joint disease that develops in the elderly. The worldwide prevalence continues to rise, leading to pain and disability in older ages. Osteoarthritis can be diagnosed by using plain film X-ray combined with clinical appearance and structural features. The imbalance between cartilage synthesis and degradation has been explained in the development of osteoarthritis, which is associated with chondrocyte death. There are many cytokines and biological markers related to the disease. The present review provides a background and discusses the known biological markers that are related to developing osteoarthritis. These include advance glycation end products, glutathione and glycosaminoglycans.


In certain digital gaming subcultures, specific games are extended and enhanced by players who create "mods", or modifications, that add new artwork, new scenarios, and even new rules. "Modders" meet in online communities that foster engagement through the discussion and self-publication of mods, and these can keep interest in a given game going years after it is released. Most importantly, modding allows players to challenge and subvert dominant discourses, and to foster cultures of inclusivity. These DIY efforts could be adapted by academic publishers, particularly those focused on design research, to encourage sustained engagement with scholarly materials. This article discusses the history of modding, provides examples, and sketches one online modding community in detail. It then makes the argument that modding is a form of end-user engagement of the sort advocated by scholars such as Gerald Fischer, and compares modding to other online academic publishing efforts, such as webtexts.


Graph based multi-view clustering has been paid great attention by exploring the neighborhood relationship among data points from multiple views. Though achieving great success in various applications, we observe that most of previous methods learn a consensus graph by building certain data representation models, which at least bears the following drawbacks. First, their clustering performance highly depends on the data representation capability of the model. Second, solving these resultant optimization models usually results in high computational complexity. Third, there are often some hyper-parameters in these models need to tune for obtaining the optimal results. In this work, we propose a general, effective and parameter-free method with convergence guarantee to learn a unified graph for multi-view data clustering via cross-view graph diffusion (CGD), which is the first attempt to employ diffusion process for multi-view clustering. The proposed CGD takes the traditional predefined graph matrices of different views as input, and learns an improved graph for each single view via an iterative cross diffusion process by 1) capturing the underlying manifold geometry structure of original data points, and 2) leveraging the complementary information among multiple graphs. The final unified graph used for clustering is obtained by averaging the improved view associated graphs. Extensive experiments on several benchmark datasets are conducted to demonstrate the effectiveness of the proposed method in terms of seven clustering evaluation metrics.


South Africa is a mining country, and one of the leading gold mining countries in the world. Mining activities tend to brit:lg other minerals and elements to the surface in addition to the desired mineral. In gold mining, one of these metals is Uranium which is both toxic and radioactive. Uranium decay to form other radioactive daughters and the radioactivity may be high enough to cause some health concerns to the public residing next to where this waste material is being dumped. In this study, soil and vegetation samples were collected from the Princess Gold mine dump in Roodepoort, South Africa, to evaluate the transfer of radionuclides and toxic elements from the mine dump to the vegetation at and around the dump. The samples were analyzed and the data was then used to estimate the potential radiological and toxicological impact of the mine dump to the community located next to it. The concentration of all essential elements in plant leaves of three species, A. pycnatha, E. globu/us and Hyparrhenia spp. were within the normal levels found in the species. The concentrations of toxic elements were slightly elevated, especially that of uranium and lead. There is a transfer of radionuclides and toxic elements from the mine dump to the plants and the transfer rates vary from species to species and from one sampling point to the other. The potential toxicological impact of both essential and toxic elements was estimated using default transfer parameters from the IAEA and the essential elements were within acceptable limits in leafy vegetables grown in home gardens while the concentration of uranium and lead were high, 1.88 and 0.144 [!g/g, respectively. The MTL in food for the two metals are 0.3 and 0.005 [!g/g respectively. The potential exposure of the population from ingestion of meat and milk from cattle feeding on pasture contaminated by radionuclides from the mine dump, as well as the consumption of sheep feeding in the same pasture was estimated. The study showed that consumption of milk and meat from such cattle will lead to a dose of 3.6 ± 2.0 mSv/a and 2.6 ± 1.6 mSv/a respectively. The dose received from consumption of leafy vegetables grown in contaminated soil was insignificant for people above the age of 1 year and 278 [!Sv/a for those below 1 year.


American school boards, parent teacher associations, and other school forums are crucial sites for participatory and deliberative democracy, yet they often involve debilitating inequities of power among school officials and parents, adults and students, and parents from more and less privileged backgrounds. In this interview, John Landesman, a Senior Associate at Everyday Democracy, discusses how he addresses power differences in dialogues aimed at improving parental participation and student learning in a diverse school district outside Washington, DC. Landesman argues that developing a robust equity strategy from the start is the only way to meet the aims of dialogue that strives to include a variety of perspectives. Landesman also shares insights into how to practice equity at each stage of organizing a dialogue, from inclusive recruitment and retention of participants, to forum design and facilitation, to evaluating and implementing the group's plans. Like many contributors to this issue, he argues that specific equity strategies should flow from the goals of a particular dialogue. He also discusses how Everyday Democracy has employed affinity group discussions, which create safe places for members of non-dominant groups to speak with each other as one stage of a community-wide dialogue.


Background The myeloproliferative neoplasms, essential thrombocytosis, polycythemia vera and primary myelofibrosis, share the same acquired genetic lesion, but the concept of JAK2 V617F serving as the sole lesion responsible for these neoplasms is under question, and there has been interest in identifying additional mutations that may contribute to disease pathogenesis. Because ASXL1 lesions have been increasingly identified in myeloid neoplasms, we examined the relationships of ASXL1 mutation or deletion to both clinical phenotype and associated molecular features in 166 patients with myeloproliferative neoplasms. Design and Methods Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia. Pyrosequencing assays were designed to determine the allele percentages of JAK2 V617F (G5073770T), ASXL1 2475dupA, and ASXL1 2846_2847del in neutrophil genomic DNA samples. Clinical and laboratory characteristics of patients with wild-type and ASXL1 mutations were then compared. Results We identified nonsense mutations or hemizygous deletion of ASXL1 in 36% of the patients with myelofibrosis, but very rarely among those with polycythemia vera or essential thrombocytosis. Among the patients with myelofibrosis, those with ASXL1 lesions were not distinguished from their wild-type counterparts with regard to JAK2 V617F status, exposure to chemotherapy or evolution to leukemia. Myelofibrosis patients with ASXL1 lesions were more likely to have received anemia-directed therapy compared to those without lesions [15/26 (58%) versus 11/39 (23%); P=0.02]. Using serial banked samples and quantitative ASXL1 mutant allele burden assays, we observed the acquisition and accumulation of ASXL1 mutations over time in two patients with post-essential thrombocytosis myelofibrosis. Conclusions ASXL1 haploinsufficiency is associated with a myelofibrosis phenotype in the context of other known and unknown lesions, and disruption of ASXL1 function may contribute to the disease pathogenesis of myelofibrosis.