Using a database that includes the universe of individuals and establishments in Denmark over the period 1991-2008 we analyze the effect of a large inflow of non-European (EU) immigrants on Danish workers. We first identify a sharp and sustained supply-driven increase in the inflow of non-EU immigrants in Denmark, beginning in 1995 and driven by a sequence of international events such as the Bosnian, Somalian and Iraqi crises. We then look at the response of occupational complexity, job upgrading and downgrading, wage and employment of natives in the short and long run. We find that the increased supply of non-EU low skilled immigrants pushed native workers to pursue more complex occupations. This reallocation happened mainly through movement across firms. Immigration increased mobility of natives across firms and across municipalities but it did not increase their probability of unemployment. We also observe a significant shift in the native labor force towards complex service industries in locations receiving more immigrants. Those mechanisms protected individual wages from immigrants competition and enhanced their wage outcomes. While the highly educated experienced wage gains already in the short-run, the gains of the less educated built up over time as they moved towards jobs that were complementary to those held by the non-EU immigrants. Mette Foged Department of Economics Univertsity of Copenhagen Øster Farigmagsgade 5, building 26 1353 Copenhagen K Denmark email@example.com Giovanni Peri Department of Economics University of California, Davis One Shields Avenue Davis, CA 95616 and NBER firstname.lastname@example.com An online appendix is available at: http://www.nber.org/data-appendix/w19315


Written during Karl Marx's brilliant career as a polemical journalist, these blazing pieces tackle subjects ranging from the strikes of angry British workers to insurrection in Europe, from the American Civil War to the misery of colonial rule in India, demonstrating the radical spirit and outrage at social injustice that would make him one of the most influential political philosophers of all time. Throughout history, some books have changed the world. They have transformed the way we see ourselves - and each other. They have inspired debate, dissent, war and revolution. They have enlightened, outraged, provoked and comforted. They have enriched lives - and destroyed them. Now Penguin brings you the works of the great thinkers, pioneers, radicals and visionaries whose ideas shook civilization and helped make us who we are.


Objectives: A diet that is high in fat and low in carbohydrates is advocated in the recently published The Real Meal Revolution. A suggestion was made in this publication that seed oils are toxic. The authors stated that available seed oils on the South African market were high in trans-fatty acid (TFA), as well as being genetically modified, and thus should be avoided. We compared three oils, i.e. canola, sunflower and olive oil, against internationally accepted standards, to determine the quality of these oils using gaschromatographic analysis, to determine whether or not there was any foundation to the statement pertaining to the toxicity of South African seed oils. Reported parameters included the fatty acid profile, TFA content, peroxide level and conjugated diene (CD) content. Design: Samples were purchased from local retail stores. Two independent researchers de-identified the oils, and stored them in numbered containers under nitrogen until commencement of the analysis. Hence, a blind sample of oils was received. Outcome measures: Twelve (n = 12) olive oil, 15 (n = 15) canola oil and 7 (n = 7) sunflower oil samples were subjected to analysis. CD and peroxide levels were conducted spectrophotometrically, and fatty acid content determined by gas liquid chromatography. Results: The total TFA content of the three types of sampled oils was below 0.5%, and the peroxide (meq O /kg) and CD levels (µmol/g) were within allowable limits, as described in the Codex Standard for Named Vegetable Oils, as well as previous publications. Conclusion: The results demonstrated that the South African seed oils included in this analysis contained a negligible amount of TFA, adhered to international recommendations with respect to fatty acid content, and were well within the safe range for oxidation products. Therefore, the statement that South African seed oils are toxic is inaccurate, unscientific and without merit.


Genetic programming (GP) systems have traditionally used a fixed training population to evolve best-of-run programs according to problem-specific fitness criteria. The ideal GP training population would be sufficiently representative of each of the potentially difficult situations encountered during subsequent program use to allow the resulting best-of-run programs to handle each test situation in an optimized manner. Practical considerations limit the size of the training population, thus reducing the percentage of situations explicitly anticipated by that population. As a result, best-of-run programs may fail to exhibit sufficiently optimized performance during subsequent program testing. This paper summarizes an investigation into the effects of creating a new randomly generated training population prior to the fitness evaluation of each generation of programs. Test results suggest that this alternative approach to training can bolster generalization of evolved solutions, improving the mean program performance while significantly reducing variance in the fitness of best-of-run programs.


The inscribed landscape serves as the central figure in the fiction and poetry of Thomas Hardy, from the images that stand out like "gilded letters upon the dark tablet of surrounding Egdon" in The Return of the Native to those "written on terrestrial things" in the poem "The Darkling Thrush." This paper concentrates on the use of writing imagery in the novels that make up the first half of Hardy9s career as a writer. Although it can be traced to the tradition of writing metaphors described by E. R. Curtius, this body of imagery is give particular freshness and depth in Hardy9s work, where it is organically related ot other visual patterns. It connects ideas of perception to patterns of individual and historical development, as experiences inscribe themselves on faces and lives. It also aids in and comments on the project of extracting meanings from sensation, which is itself central to Hardy. Further, Hardy9s writing metaphors, by creating a "world as text," determine relations between his texts and the world they represent, placing his characters as secondary readers in the text and redefining text and world as objects of interpretation. Hardy9s use of writing imagery, therefore, not only rehabilitates a commonplace figure but throws light on the function of metaphor in the discovery of meaning.


Organizations in the United States and throughout the world struggle with religious expression in the workplace. Though the US Constitution provides citizens with freedom of religion, as does the Universal Declaration of Human Rights, adopted by 169 Countries, this right to free exercise of religion has been translated to freedom from religion in many organizations around the world. Religion, a salient part of personal identity for more than 80% of the world's population, gets hidden if one's religion does not contain visible garb. The ability to learn from one another, put aside stereotypes, and discover commonalities may be denied to individuals. This paper examines the concept of freedom of religion or freedom from religion through the lens of two stories drawn from academic and international settings in the United States, Sweden, Egypt, and Israel attempting to highlight the difficulties of bringing religious faith into more active engagement with organizations. Categorical themes are developed to understand why freedom from religion occurs within these settings. Themes include contextual norms, trust, fear, privacy concerns, and a lack of tools.


Microbial processes applied to mining operations are gaining increasing interest in the last years. Potential and current applications include the mining of gold, copper and other heavy metals, desulfurization of coal and oil, tertiary recovery of oil and biosorption of metal ions. Currently, bacterial leaching of copper and biooxidation of refractory gold concentrates are wellestablished large-scale processes that are carried on using heaps and tank reactors. Heap operation is simple and adequate to handle large volumes of minerals, but their productivity and yields are limited because of the severe difficulties in exerting an adequate process control. On the other hand, reactors can economically handle moderate volumes of material, but they allow for a close control of the variables involved, rendering significantly better performances. This paper reviews the basis of reactor selection and design for bioleaching processes. Special attention is given to the influence of oxygen and carbon dioxide mass transfer, process stoichiometry, solids suspension and slurry homogeneity, and the use of bioreactors in gold mining. It is concluded that the future of reactors in biomining is promising and that new applications, such as the bioleaching of copper concentrates, will soon be a reality.


Awareness and shared knowledge are important ingredients of successful coordination in software engineering projects, and especially when team members are distributed. Although various coordination mechanisms and knowledge sharing recommendations for cross-site collaboration have been proposed, spreading awareness among distributed team members in a global software project has proven to be challenging in practice. In this paper we discuss our findings from conducting three focus groups on knowledge management in global software collaborations in two international organizations. We discuss various awareness needs in globally distributed collaborations that were not addressed by the organizations, and conclude that best practices and tools proposed in related research are not widely used. On the basis of our empirical findings we suggest future research directions and share recommendations for practical improvements.


The study examines the effects of applying fair value accounting under IAS 40 on the volatility of earnings. It studies how the addition of unrealized gains and losses in the income statement might affect the incremental explanatory power of earnings. The study covers the period of 2002-2009 and the data collected from the Jordanian Shareholding Companies listed on Amman Stock Exchange. In this study the valuation model of Ohlson (1995) and the technique of Theil (1971) have been utilized. The results point out that unrealized gains and losses affect the net income and the results of cross-sectional regression indicate that net income and book values jointly and individually are positively and significantly related to stock prices. The incremental information of net income is greater than that of book values and the addition of unrealized gain in income increases the explanatory power of the model.


Between 1962 and 1973, thousands of refugees crossed from the Indonesian-controlled western half of the island of New Guinea into the Australian-controlled eastern half. The United Nations High Commissioner for Refugees (UNHCR) refrained from becoming involved in the issue, and from publicly criticizing the Australian government over its response to West Papuan asylum seekers. In return, the Australian government committed itself to keeping the High Commissioner informed about developments in New Guinea on the understanding that it would provide information on a strictly confidential basis. The article explores the High Commissioner's possible motives for effectively condoning Australia's refugee policies in Papua and New Guinea. It demonstrates the relevance of this historical case study for our understanding of current Australian policies and for evaluating the relationship between the UNHCR and governments.


The mitochondrial state of a tumor cell prior to chemotherapy may help determine how well it responds to drug treatment. Decades after their introduction into the clinic, cytotoxic chemotherapeutic drugs continue to be the mainstay of cancer patient care. Why chemotherapeutic drugs are effective in some tumors and not others is not fully understood. Ni Chonghaile et al. (see the Perspective by Reed) hypothesized that differences in chemotherapeutic response might be due to pretreatment differences in the readiness of tumor cells to undergo apoptosis (a form of cell death), a measurable property that they call "mitochondrial priming." Consistent with this idea, patients with highly primed cancers were found to have a superior clinical response to chemotherapy. In vitro manipulations that increased mitochondrial priming in tumor cells enhanced their sensitivity to chemotherapy. T. Ni Chonghaile, K. A. Sarosiek, T.-T. Vo, J. A. Ryan, A. Tammareddi, V. Del Gaizo Moore, J. Deng, K. C. Anderson, P. Richardson, Y.-T. Tai, C. S. Mitsiades, U. A. Matulonis, R. Drapkin, R. Stone, D. J. DeAngelo, D. J. McConkey, S. E. Sallan, L. Silverman, M. S. Hirsch, D. Ruben Carrasco, A. Letai, Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science 334, 1129–1133 (2011). [Abstract] [Full Text] J. C. Reed, Priming cancer cells for death. Science 334, 1075–1076 (2011). [Abstract] [Full Text]


Wajir County is one of the arid and semi arid counties in Kenya that has been experiencing the negative effects of recurrent drought throughout. Oxfam GB an international Non Governmental Organization (NGO) has been implementing a Community Managed Disaster Risk Reduction Programme (CMDRR) by employing Participatory Capacity and Vulnerability Assessment(PCVA). This approach uses various participatory tools to gauge people's exposure to and capacity to resist natural hazards. The study sought to compare the impact of PCVA in two villages. The purpose of the task was to examine whether there is a difference in livelihood between those pastoralists who have participated in PCVA and those who have not. Specifically, the study aimed at finding whether there is a difference in ownership of basic life sustaining properties such as cattle, sheep, goats, and camel. It also aimed at finding out whether the community members have realized any change in their lives in regard with food security, economic growth and increase in animals since 2011 when PCVA was introduced. This research was a comparative study comparing two villages (one with PCVA and one which had not received this intervention). The PCVA beneficiaries were asked to rate the interventions in terms of risk reduction strategies, livelihood improvement strategies, and drought mitigation strategies. At the same time the study sought to establish whether PCVA is a factor in livelihood improvement by doing Chi-Square tests on animal ownership and level of satisfaction in economic growth, increase in livestock and food security. On establishing whether PVCA had increase ownership of animals the study revealed that the PVCA group had a higher number of animals as compared with the group without PVCA. This could be attributed to the intervention meaning that mitigation measures put in place by PVCA could be a factor in the high numbers of animals owned by the PVCA group. Comparatively there is a high level of satisfaction on the economic growth, livestock increase and food security among the PVCA participating group compared to the group without PVCA.
Chi-Square test of Independence was used to test whether or not 1)There is an association between PVCA and owning animals.2)There is an association between PVCA and satisfaction on the development achieved so far. In the two tests the findings were that PVCA is not associated the number of animals own in Wajir. Neither is the program associated with the level of satisfaction expressed the people of Wajir over the development achieved so far. Meaning that PVCA has made little if any impact on the livelihoods of the people of Wajir.PCVA is not associated with the number of animals that people owned because pastoralism has been the key agricultural production system in the dry lands and remains dominant livelihood base of the people of Wajir (99%).The level of satisfaction expressed on the changes achieved in terms on increase in animals, food security and economic growth is not associated because PCVA might not be different than the previous approach used before and the study recommended that sustainability, ownership and stakeholder involvement diversification of livelihood and pro-pastoral policies and advocacy are crucial in the successful implementation of this approach


This study considers the weldability of Ti-6Al-4V alloys formed by various powder consolidation methods. Samples were prepared from commercially sourced pre-alloyed Ti-6Al-4V powder using both conventional press-and-sinter (PS) and the new novel resistance-heated pressing (RHP) methods. Fusion welding was executed by the gas tungsten arc (GTA) process with arc stability assessed in-situ by observations of the arc as well as monitoring of transient arc voltage. Results indicated equivalent arc stability between samples of RHP and commercially sourced wrought material while samples formed by PS showed high instability in arc initiation, attributed to high levels of porosity. Post weld analysis of mechanical hardness in powder based samples revealed no significant deviation in weld metal properties from welds conducted on commercially sourced wrought material. In all cases weld microstructures typical of Ti-6Al-4V alloys were observed with significant grain growth in the fusion and heat affected zones. Samples prepared by PS methods showed internal porosity due to gas evolution upon solidification, which may again be attributed to the highly porous initial microstructure.


This paper introduces a bivariate version of the generalized accelerated failure time model. It allows for simultaneity in the econometric sense that the two realized outcomes depend structurally on each other. Another feature of the proposed model is that it will generate equal durations with positive probability. Our approach takes a stylized economic model that leads to a univariate generalized accelerated failure time model as a starting point. In this model, agents decide when to transition from an initial state to a new one, and the covariates influence the difference in the utility flow in the two states. We introduce simultaneity by allowing the utility flow to depend on the status of the other person. The econometric model is then completed by assuming that the observed outcome is the Nash bargaining solution in that simple economic model. The advantage of this approach is that it includes independent realizations from the generalized accelerated failure time model as a special case, and deviations from this special case can be given an economic interpretation. We established identification under assumptions that are similar to those in the literature on nonparametric estimation of duration models. We illustrate the model by studying the joint retirement decisions in married couples using the Health and Retirement Study. In that example, it seems reasonable to allow for the possibility that each partner's optimal retirement time depends on the retirement time of the spouse. Moreover, the data suggest that the wife and the husband retire at the same time for a nonnegligible fraction of couples. The main empirical finding is that the simultaneity is economically important. In our preferred specification, the indirect utility associated with being retired increases by approximately when one's spouse retires.
Interdependent durations joint retirement interactions and simultaneity J26 C41 C3


Uses of the propensity score to obtain estimates of causal effect have been investigated thoroughly under assumptions of linearity and additivity of exposure effect. When the outcome variable is binary relationships such as collapsibility, valid for the linear model, do not always hold. This article examines uses of the propensity score when both exposure and outcome are binary variables and the parameter of interest is the marginal odds ratio. We review stratification and matching by the propensity score when calculating the Mantel–Haenszel estimator and show that it is consistent for neither the marginal nor conditional odds ratio. We also investigate a marginal odds ratio estimator based on doubly robust estimators and summarize its performance relative to other recently proposed estimators under various conditions, including low exposure prevalence and model misspecification. Finally, we apply all estimators to a case study estimating the effect of Medicare plan type on the quality of care received by African-American breast cancer patients.


Vegetation water use is closely related to its biophysical functioning and is often under stress from various environmental factors. However, commonly used root water uptake models only consider the stress from root zone moisture availability. There is a need to incorporate the stress from both the above-ground factors and root zone water condition. In this study, a newly developed coupled supply- and demand-induced (S&D) root water uptake model is examined with measurements on two tree species, Guihua in the subtropical monsoon climate and Drooping Sheoak in the Mediterranean climate. The results show that the S&D model outperforms a supply-constraint water stress function (the S-shape model) for both studied species. The S&D model predicts 67% and 84% temporal variability in the measured water stress for Guihua and Drooping Sheoak, respectively. The improvement of the S&D model over the S-shape model is more significant for Guihua than for Drooping Sheoak, which might be associated with the specific climate conditions. A two-step parameterization approach is adopted in this study for the S&D model, and is recommended for future applications. These results further support the validity of the S&D model, and should be considered for the root water uptake modeling.


There are continuous research and practical interest to combine different renewable sources within one Smart Grid network. The paper aims to estimate the influence of key economic and social drivers of renewable energy and Smart Grid promotion in OECD member countries. The random effect of the generalized least squares method was used to estimate the empirical model based on the World Bank, OECD, Heritage Foundation, and World Energy Council datasets for a panel of 36 OECD counties. For the empirical estimation, the dependent variables considered are energy renewable electricity output and energy trilemma index, taken as two proxies for Smart Grid development. The results suggest that an increase in GDP p. c. in national economies by 10,000 USD leads on average to a 3.9% decrease in renewable electricity output during 2001–2015. The richer the society, the less renewable energy sources were used for power generation in a group of OECD countries. The last is also supported by the fact that gross fixed capital formation treated as a percentage value of GDP is negatively correlated with structural changes in renewable energy output. The empirical conclusion is that during the study period, OECD countries were mainly oriented to economic growth, which was achieved by consuming non-renewable energy resources, and limited attention was paid to sustainability and Millennium Development Goals. The paper provides policy recommendations for Smart Grid development and points in the future research within OECD countries.
AcknowledgmentsComments from the Editor and anonymous referees have been gratefully acknowledged. Leonid Melnyk gratefully acknowledges financial support from the Ministry of Education and Science of Ukraine (0118U003578). Oleksandra Kubatko gratefully acknowledges financial support from the Ministry of Education and Science of Ukraine (0119U100766) and National Research Foundation of Ukraine (2020.01/0135).


In the past, research on changes in relative importance among broad three sectors— agriculture, industry, and service—showed general patterns of a country's structural transformation along with economic development. However, there has been devoid of empirical studies investigating in the structural change within the manufacturing sector, which often plays a role of the engine in economic growth. Our analysis looks into the evolution of production structures prevailing at certain development stages while controlling for country-given characteristics such as size, resource endowments, and others. This can provide an industrial policy framework for structural change facilitation that can lead to sustained economic development in the long run.


Background: The provision of assistive devices (ADs) to enable function is a well-established component of occupational therapy (OT) practice. However, multiple client and therapist factors prevent the utilization of ADs in practice. Objectives: This study aimed to explore the utilization of ADs in OT practice in Tamil Nadu (TN). Study Design: The survey research design was used to conduct this study. A ten-item electronic survey was developed based on the research question. Methods: The survey was E-mailed to 295 occupational therapists in TN identified through convenience sampling. The survey link was also shared on four WhatsApp Messenger groups (Tamil Nadu Branch of All India Occupational Therapists' Association Official Group, OTist Group, Clinic OT, and Santosh Alumni) with many occupational therapists belonging to TN (snowball sampling). Data were collected between August 29, 2019, and September 20, 2019. Results: Thirty-five occupational therapists responded to the survey. Writing and eating utensils were the commonly prescribed ADs in TN OT practice. Client factors, cultural factors, lack of availability, cost, and therapists' skill may contribute to the limited usage of ADs in Indian OT practice. Innovating low-cost culturally acceptable ADs, educating stakeholders, and training practitioners on how to prescribe/utilize ADs in practice may mitigate the barriers related to ADs use. Conclusion: The usage of ADs in TN OT practice is limited. Multiple factors affect the utilization of ADs in the Indian context of practice. A multipronged approach focusing on innovative device development, advocacy, and skill development is needed to promote the utilization of ADs in Indian OT practice.


CO2 (dry) reforming of methane (DRM) has received much attention as an important process for the transformation and applications of two greenhouse gases (CH4 and CO2). In the present study, non-precious monometallic molybdenum nitride Mo2N and bimetallic molybdenum nitrides Ni3Mo3N and Co3Mo3N were synthesized and used as catalysts for DRM. It was found that the Mo2N, Ni3Mo3N and Co3Mo3N materials were catalytically active in the DRM reaction above 550 °C. Compared to the monometallic nitride Mo2N, the bimetallic nitrides Co3Mo3N and Ni3Mo3N showed enhanced catalytic activity, stability and resistance to oxidation. Particularly, Co3Mo3N exhibited the highest activity and stability among the three samples, which could be due to three factors, namely, the synergistic effect between the Mo and interstitial metal Co in the interstitial structure, the roughly equal adsorption capacities and consumption rates of reactants CO2 and CH4 and their increment on the surface of the catalyst at high reaction temperatures, as well as a possible conversion balance on the active centers established. The results suggest that the low-cost Co3Mo3N is a promising candidate for DRM.


Introduction The dramatic events of meiotic recombination culminate in the exchange of genetic information between parental chromosomes and ensure the production of genetically distinct gametes. Recombination is initiated by the formation of programmed DNA double-strand breaks (DSBs), and most DSBs occur at discrete hotspots defined by the DNA binding specificity of the PRDM9 protein. The tandem array of PRDM9 zinc fingers that binds DNA is highly polymorphic, and different variants have different DNA binding preferences. Subsequent to binding, PRDM9 is thought to modify the local chromatin environment and to recruit SPO11 for DSB formation. Meiotic DSBs are predominantly repaired through homologous recombination, giving rise to either genetic crossovers, where a reciprocal genetic exchange occurs between homologous chromosomes, or noncrossovers. Meiotic DSB maps in human male individuals. In meiotic cells, the formation of programmed meiotic DSBs facilitates the subsequent exchange of genetic material between parental homologous chromosomes. All current methods to study the sites of meiotic recombination rely on detection of these genetic exchanges. The DMC1 protein binds to DNA around meiotic DSBs, and in this work, we used testis biopsies from individual males to pull down the DNA bound by the DMC1 protein. We thus identified the sites of meiotic DSBs in five individual males. Analysis and comparison of the resultant PRDM9-specific, personal genome-wide maps offers insights into the mechanisms that initiate meiosis, genome evolution, crossover formation, human population structure, and predisposition to genomic disorders. Rationale Despite recent progress in our understanding of recombination hotspot formation, the initiation of recombination remains poorly understood. Current approaches to study the early steps of meiotic recombination in humans primarily detect genetic crossovers, only one of the possible outcomes of DSB repair. Furthermore, these methods are limited by resolution, by sex and population averaging, or by an inability to extend the analysis genome-wide. To overcome these limitations, we built and analyzed high-resolution, individual-specific maps of meiotic DSBs in the human genome. Results We report the maps of meiotic DSBs in five males: two homozygous for the most common PRDM9 allele (PRDM9A) and three heterozygous for the PRDM9A allele and for the less frequent PRDM9B or PRDM9C alleles. We find that PRDM9A and PRDM9B define similar DSB hotspots, whereas the PRDM9C allele has a distinct specificity. A comparison of DSB hotspot maps with linkage disequilibrium (LD)–based estimates of recombination rates in the human population indicates that the LD map is a superimposition of PRDM9 allele-specific DSB maps and that the contribution of individual maps is proportional to the PRDM9 allele frequency in modern Africans. In individuals with identical PRDM9 alleles, over 5% of DSB hotspots vary in strength, yet less than half of this variation could be explained by sequence variation at putative PRDM9 binding sites. We also find that PRDM9 heterozygosity affects hotspot strength. In human males, DSBs, like crossovers, occur more frequently at subtelomeric regions, and the crossover rate is directly proportional to our estimate of DSB frequency. This indicates that DSB initiation frequency is a major driver of the crossover rate in human males. We detect distinct signatures of GC-biased gene conversion and of recombination-coupled mutagenesis at DSB hotspots. In addition, DSB hotspots are enriched at the breakpoints of copy number variants that arise via homology-mediated mechanisms. Such variants may give rise to genomic disorders, and indeed, we find that meiotic DSBs defined by PRDM9A often coincide with disease-associated chromosomal breakpoints. Conclusions Our genome-wide recombination initiation maps in individual human males offer unprecedented resolution of recombination initiation sites defined by specific alleles of the PRDM9 protein. Our analysis indicates that DSB frequency is a primary determinant of crossover frequency, and that factors other than PRDM9 modulate the frequency of recombination initiation. We also find that meiotic DSB repair and subsequent recombination affect the genome sequence both locally and at the level of structural rearrangements. Taken together, these data provide a foundation for future studies of genetic recombination, meiosis, and genome stability. DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here, we present high-resolution maps of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors may dictate the efficiency of DSB formation. We find evidence for both GC-biased gene conversion and mutagenesis around meiotic DSB hotspots, while frequent colocalization of DSB hotspots with chromosome rearrangement breakpoints implicates the aberrant repair of meiotic DSBs in genomic disorders. Furthermore, our data indicate that DSB frequency is a major determinant of crossover rate. These maps provide new insights into the regulation of meiotic recombination and the impact of meiotic recombination on genome function. Mapping human male meiotic recombination sites reveals their influence on genome evolution and genetic disease. [Also see Perspective by de Massy] Mapping recombination in individual human males Sperm and eggs form from diploid cells that contain two copies of our genomic DNA. The haploid germ cells must undergo a special cell division, meiosis, which halves their DNA content. Meiosis involves a DNA recombination step between parental chromosomes. Recombination is initiated by a DNA double-strand break, which can exchange DNA between the chromosomes, a process that drives human genetic variation. Pratto et al. mapped meiotic recombination sites in individual human males (see the Perspective by de Massy). Recombination hotspots were influenced by variants of the histone-lysine N-methyltransferase protein, PRDM9, as well as by other factors. The recombination sites also influence genome evolution and the incidence of genetic disease. Science, this issue 10.1126/science.1256442; see also p. 808


The central aim of this paper is to explore the mechanisms that teachers of professional practice use with their students to ease them into employment. In particular, it will concentrate on how teachers help students to prepare their CVs and portfolios in the subject of design. The methodological approach will be qualitative rather than quantitative. In addition to an analysis of appropriate literature on the CV and the current practice of portfolio preparation, this paper will employ evidence gathered from interviews with a number of individuals who teach professional practice to design students, but who also have a role in independently running their own design companies. Using a semi-structured format, interviews will be conducted with the design companies El Ultimo Grito and Design Direction, both of whose directors are also involved in the teaching of professional practice to students. The evidence from these interviews will be collected and used to suggest and consider developments in the teaching materials currently used to guide students on the production and design of their CVs and portfolios. The aim is to guarantee that students are then better able to project their skills to employers, and hence to ensure that the teaching of professional practice in design may help ease a greater number of design students into employment.


OBJECTIVE Although there is increasing recognition of the importance of cervical spinal sagittal balance, there is a lack of consensus as to the optimal method to accurately assess the cervical sagittal alignment. Cervical alignment is important for surgical decision making. Sagittal balance of the cervical spine is generally assessed using one of two methods; namely, measuring the angle between C-2 and C-7, and drawing a line between C-2 and C-7. Here, the best method to assess sagittal alignment of the cervical spine is investigated. METHODS Data from 138 patients enrolled in a randomized controlled trial (Procon) were analyzed. Two investigators independently measured the angle between C-2 and C-7 by using Harrison's posterior tangent method, and also estimated the shape of the sagittal curve by using a modified Toyama method. The mean angles of each quantitative assessment of the sagittal alignment were calculated and the results were compared. The interrater reliability for both methods was estimated using Cronbach's alpha. RESULTS For both methods the interrater reliability was high: for the posterior tangent method it was 0.907 and for the modified Toyama technique it was 0.984. For a lordotic cervical spine, defined by the modified Toyama method, the mean angle (defined by Harrison's posterior tangent method) was 23.4° ± 9.9° (range 0.4°-52.4°), for a kyphotic cervical spine it was -2.2° ± 9.2° (range -16.1° to 16.9°), and for a straight cervical spine it was 10.5° ± 8.2° (range -11° to 36°). CONCLUSIONS An absolute measurement of the angle between C-2 and C-7 does not unequivocally define the sagittal cervical alignment. As can be seen from the minimum and maximum values, even a positive angle between C-2 and C-7 could be present in a kyphotic spine. For this purpose, the modified Toyama method (drawing a line from the posterior inferior part of the vertebral body of C-2 to the posterior upper part of the vertebral body of C-7 without any measurements) is a better tool for a global assessment of cervical sagittal alignment. Clinical trial registration no.: ISRCTN41681847 ( https://www.isrctn.com ).


This paper attempts to provide conclusive evidence of regional variations in demand be¬haviour in India using the Restricted Non Linear Preference System. Also the importance of household composition is brought out clearly via its influence on optimal commodity taxes for India. This is done by recognizing each of the chosen 16 Indian states separately and esti¬mating tax rates for them, while incorporating demographic variables. The results show con¬siderable variations in not only the estimated tax rates, but also in the demand behaviour as revealed by response of tax rates to changes in revenue requirements and changes in a social planner's aversion to inequality. In other words, the estimated tax rates are extremely sensi¬tive to the degree of aversion to inequality and the required revenue; the response of each state to these changing parameters is also non uniform. Our results reveal that indirect taxes are ineffective in redistributing income in the majority of the states under consideration.


There is evidence for differential stability in personality trait differences, even over decades. The authors used data from a sample of the Scottish Mental Survey, 1947 to study personality stability from childhood to older age. The 6-Day Sample (N = 1,208) were rated on six personality characteristics by their teachers at around age 14. In 2012, the authors traced as many of these participants as possible and invited them to take part in a follow-up study. Those who agreed (N = 174) completed a questionnaire booklet at age 77 years, which included rating themselves and asking someone who knew them well to rate them on the same 6 characteristics on which they were rated in adolescence. Each set of 6 ratings was reduced to the same single underlying factor, denoted dependability, a trait comparable to conscientiousness. Participants' and others' older-age personality characteristic ratings were moderately correlated with each other, and with other measures of personality and wellbeing, but correlations suggested no significant stability of any of the 6 characteristics or their underlying factor, dependability, over the 63-year interval. However, a more complex model, controlling rater effects, indicated significant 63-year stability of 1 personality characteristic, Stability of Moods, and near-significant stability of another, Conscientiousness. Results suggest that lifelong differential stability of personality is generally quite low, but that some aspects of personality in older age may relate to personality in childhood.


Climate-related foreign aid is on the rise, with signatories to the Paris Climate agreement pledging $100 billion annually to promote mitigation and adaptation in recipient countries. While this seems like a welcome development, we have little evidence that climate aid actually encourages recipients to adopt climate legislation. In this article, we examine the relationship between climate aid and recipient climate policy. Using multiple measures of each, we find no evidence that the former is systematically related to the latter. Although this suggests that climate aid is ineffective, this conclusion must be qualified due to the poor quality of both climate aid and climate policy data. More definitive conclusions will require more accurate coding of climate aid as well as better climate policy measures that distinguish truly consequential policies from less consequential ones.


The university course timetabling problem (UCTP) is a combinatorial optimization problem, in which a set of events has to be scheduled into time slots and located into suitable rooms. The design of course timetables for academic institutions is a very difficult task because it is an NP-hard problem. This paper investigates genetic algorithms (GAs) with a guided search strategy and local search (LS) techniques for the UCTP. The guided search strategy is used to create offspring into the population based on a data structure that stores information extracted from good individuals of previous generations. The LS techniques use their exploitive search ability to improve the search efficiency of the proposed GAs and the quality of individuals. The proposed GAs are tested on two sets of benchmark problems in comparison with a set of state-of-the-art methods from the literature. The experimental results show that the proposed GAs are able to produce promising results for the UCTP.


Introduction: HbE is the commonest beta haemoglobin (Hb) variant in Southeast Asia. It causes a reduction in synthesis of the beta-globin E chain. Studies indicate HbE coinherited with a-thalassaemia leads to milder clinical phenotype. This study investigates the commitant inheritance of a-thalassaemia in Malays with HbE. Methods: Four hundred and fourteen (414) blood samples were screened for haemoglobinopathy using primarily the first three steps of the BHES [ (B) blood counts, blood film; (H), HPLC; (E) electrophoresis; (S), stability ] protocol. Complete blood cell analyser, Hb typing with cation exchange high-performance liquid chromatography (HPLC) and Hb electrophoresis at an alkaline pH (pH 8.5) Forty-five (10.9%) were identified as HbE trait and DNA analysis was done for deletional a-thalassaemia using a single-tube multiplex-PCR assay. Results: Among the 45 subjects with HbE trait, 4 (8.9%) were found to have alpha-thalassaemia -2 (a) (a-37 kb deletion) and 1 (2.2%) the alpha-thalassaemia-1 (a0) (---SEA 20.5 kb deletion) defects respectively. Discussion: These findings show that 11.1% of Malays with HbE inherit alpha-thalassaemia concurrently. The most prevalent interaction found was a double heterozygote for HbE /a-thalassaemia 2, followed by HbE/a-thalassaemia 1. Conclusion: Molecular screening of deletional a-thalassaemia identified its concurrent inheritance in 11.1%o of Malays who were HbE carriers. This information will guide genetic counseling and the planning of treatment modalities in patients with HbE alpha-thalassaemia.


ABSTRACT: This article describes the process of cyclotron development in Britain in the 1930s by focusing on the relationships between John D. Cockcroft, James Chadwick, and the Metropolitan-Vickers Electrical Company, Ltd. There is a difference of about one year in the completion dates of the cyclotrons built by Cockcroft at Cambridge University9s Cavendish Laboratory and by Chadwick at the University of Liverpool. This time discrepancy seems to be a consequence of the differing relationships the two men had with Met-Vick. Analysis of British cyclotron development points to three major changes that took place in scientific research: the emergence in university laboratories of researchers specializing in developing experimental instruments; alterations in the relationship between university research laboratories and companies; and the need for special funding sources to enable university laboratories to construct experimental instruments.


Existing statutes give the President and his Treasury Department broad authority to implement important elements of the administration's tax agenda without further congressional action. And yet only infrequently does the Executive Branch exercise this statutory "power to tax." Instead, the President often asks Congress to pass revenue-raising measures achieving what the President and his Treasury Department already could accomplish on their own. And even when Congress rebuffs the President's request, present and past administrations only rarely have responded by exercising the regulatory authority they already possess. Contrast this with the fact that present and past Presidents have stretched the limits of executive authority in a taxpayer-friendly direction—even over Congress's expressed preferences. This article attempts to explain the peculiar patterns of executive action and inaction observed in the tax policymaking domain. It draws on public choice theory and game theory to build a strategic model of interactions between the Executive and Legislative Branches. The model generates several counterintuitive implications. Among others: a strong anti-tax faction in Congress may increase the probability that revenue-raising regulatory measures are implemented; judicial deference to Treasury regulations may reduce lawmakers' willingness to pass revenue-raising fixes to existing tax statutes; and statutory rules requiring legislation to be "deficit-neutral" may discourage the administration from taking deficit-closing regulatory actions.


In this work, we provide a new formulation for Graph Convolutional Neural Networks (GCNNs) for link prediction on graph data that addresses common challenges for biomedical knowledge graphs (KGs). We introduce a regularized attention mechanism to GCNNs that not only improves performance on clean datasets, but also favorably accommodates noise in KGs, a pervasive issue in real-world applications. Further, we explore new visualization methods for interpretable modelling and to illustrate how the learned representation can be exploited to automate dataset denoising. The results are demonstrated on a synthetic dataset, the common benchmark dataset FB15k-237, and a large biomedical knowledge graph derived from a combination of noisy and clean data sources. Using these improvements, we visualize a learned model's representation of the disease cystic fibrosis and demonstrate how to interrogate a neural network to show the potential of PPARG as a candidate therapeutic target for rheumatoid arthritis.


Abstract A first quantitative description of the mechanical failure of surface scales was given by U. R. Evens in 1937. This approach can still form the basis for today's understanding, but the important role of physical defects is hidden in the energy term for the adhesional work to be overcome for scale failure. In the present paper, an extended approach is described that is based primarily on defect growth kinetics during high temperature exposure and relates the critical strain to scale failure to physical defect size via a 'fingerprint' parameter η. If η has been determined once for an oxide/metal system by metallography and mechanical four-point bending tests, critical oxide failure strains can be assessed simply by metallographic determination of defect sizes without additional mechanical testing. This seems to be of particular interest for the assessment of scale strain tolerance on service exposed components, e.g. in power stations. So far, the extended concept has been confirmed for Ni and Ti oxide scales; further work is currently in progress.


OBJECTIVES
We estimated the relationship between mining and tuberculosis (TB) among countries in sub-Saharan Africa.

METHODS
We used multivariate regression to estimate the contribution of mining activity to TB incidence, prevalence, and mortality, as well as rates of TB among people living with HIV, with control for economic, health system, and population confounders.

RESULTS
Mining production was associated with higher population TB incidence rates (adjusted b = 0.093; 95% confidence interval [CI] = 0.067, 0.120; with an increase of mining production of 1 SD corresponding to about 33% higher TB incidence or 760,000 more incident cases), after adjustment for economic and population controls. Similar results were observed for TB prevalence and mortality, as well as with alternative measures of mining activity. Independent of HIV, there were significant associations between mining production and TB incidence in countries with high HIV prevalence (≥ 4% antenatal HIV prevalence; HIV-adjusted B = 0.066; 95% CI = 0.050, 0.082) and between log gold mining production and TB incidence in all studied countries (HIV-adjusted B = 0.053; 95% CI = 0.032, 0.073).

CONCLUSIONS
Mining is a significant determinant of countrywide variation in TB among sub-Saharan African nations. Comprehensive TB control strategies should explicitly address the role of mining activity and environments in the epidemic.


This article explores an ancient tale of customary public rights that starts and ends with the landmark decision of Brown v Tasmania. In Brown, Australia's highest court recognised a public right to protest in forests. Harking back 800 years to the limits of legal memory, and the Forest Charter of 1217, this right is viewed through the metaphor of the lawful forest, a relational notion of property at the margins of legal orthodoxy. Inherent to this tale is the tension that pits private enclosure against the commons, a contest that endures across time and place – from 13th century struggles against the Norman legal forest, through to modern claims of rights to the city.


Multi-subject fMRI data is critical for evaluating the generality and validity of findings across subjects, and its effective utilization helps improve analysis sensitivity. We develop a shared response model for aggregating multi-subject fMRI data that accounts for different functional topographies among anatomically aligned datasets. Our model demonstrates improved sensitivity in identifying a shared response for a variety of datasets and anatomical brain regions of interest. Furthermore, by removing the identified shared response, it allows improved detection of group differences. The ability to identify what is shared and what is not shared opens the model to a wide range of multi-subject fMRI studies.


The global system of intellectual property rights (IPRs) is changing profoundly. Many developing countries have undertaken significant strengthening of their IPRs regimes. Several regional trading arrangements now address questions of regulatory convergence, particularly in IPRs. Most significant is the introduction of the agreement on trade-related intellectual property rights, or TRIPs, within the World Trade Organization (WTO). Under TRIPs, WTO members must adopt and enforce strong and non-discriminatory minimum standards of protection for intellectual property. Many developed countries are extending strong protection to controversial areas, including biotechnology and electronic databases. The movement toward much stronger global IPRs is consistent with processes of economic globalization, or the successively closer integration of national and regional markets through the reduction of barriers to trade, investment, and technology flows. In this world, knowledge creation and its adaptation to product designs and production techniques are increasingly essential for competitiveness and growth. This situation takes on political importance because the international mobility of capital and technology have risen markedly relative to that of most types of labor. In turn, globalization pays its largest rewards to creative and skilled workers and places its largest pressures on lower-skilled workers. The means by which IPRs influence FDI are complex and subtle. Furthermore, strong IPRs alone are not sufficient incentives for firms to invest in a country. If they were, recent FDI flows to developing economies would have gone mainly to sub-Saharan Africa and Eastern Europe. In contrast, China, Brazil, and other high-growth, large-market developing economies with weak protection would not have attracted nearly as much FDI. And as noted above, IPRs are an important component of the regulatory system, including taxes, investment regulations, production incentives, trade policies, and competition rules. Thus, from a policy perspective, it is the existence of a pro-competitive business environment that matters overall for FDI. This analysis points out that, in theory, investment and technology transfer do not necessarily expand with stronger intellectual property rights, but there is emerging evidence in favor of that view. It is increasingly assumed around the globe that FDI and licensing are beneficial for the recipient country and there is a strong presumption in this direction but it is not a necessary outcome in all situations. Rather, it is important that such flows result in stronger competition on local markets, which tends to promote long-run gains. In terms of policy options, freer market access, together with sensible competition rules and related regulatory systems, promise to promote the greatest net benefits from incoming investment. Thus, economies that wish to increase their attractiveness to foreign investors would be advised first to undertake significant market liberalization. While the Uruguay Round committed most countries to cutting trade barriers, further reduction of tariffs and removal of NTBs on a credible schedule would provide an important signal to foreign investors. Regional trade integration, particularly with developed economies that could be the source of additional FDI, could assist in this process. However, such agreements also bear potential for trade and investment diversion and should be considered carefully in each instance. Key words: multinational corporations, intellectual property rights, World Trade Organisation, foreign direct investment


"Why the need, in some way the urgency, of a historically retrospective number of
«ArchAlp» magazine dedicated to the houses of Alpine modernity?
The intent of this issue is to investigate the relationship between twentieth century
modernity and contemporaneity in terms of breaks and novelties, of continuity and
discontinuity, of shooting, variations and implementations, not just under the formal
and linguistic aspect. In other words, are there points of interaction, long lasting red
threads between the architectural vision of Lois Welzenbacher, Charlotte Perriand,
Carlo Mollino, and that of Peter Zumthor, Gion A. Caminada, Bernardo Bader? It is
basically a way to understand the existence of more or less long trajectories in the
way architecture has set the critical and cultural field of mountain construction, recognizing
differences and specificities.
Although these are generally well-known projects, the works published in this issue
of «ArchAlp» are not uniformly known in the territories that refer to the Alpine space.
Hence the importance of gathering together a series of architectures that have had
the potential for prototypes in order to submit them to a general and comparative
view.
Even in the absence of perhaps direct subsidiaries, the architectures presented in
these pages represent an extraordinary patrimony of design moves and strategies
which, through the internalization of experiences, deeply influenced the formation
and determination of the contemporary architectural research field in the Alpine
environment."


Network Security is a comprehensive resource written for anyone who plans or implements network security measures, including managers and practitioners. It offers a valuable dual perspective on security: how your network looks to hackers who want to get inside, and how you need to approach it on the inside to keep them at bay.

 You get all the hands-on technical advice you need to succeed, but also higher-level administrative guidance for developing an effective security policy. There may be no such thing as absolute security, but, as the author clearly demonstrates, there is a huge difference between the protection offered by routine reliance on third-party products and what you can achieve by actively making informed decisions. You'll learn to do just that with this book's assessments of the risks, rewards, and trade-offs related implementing security measures.

 + Helps you see through a hacker's eyes so you can make your network more secure.
 + Provides technical advice that can be applied in any environment, on any platform, including help with intrusion detection systems, firewalls, encryption, anti-virus software, and digital certificates.
 + Emphasizes a wide range of administrative considerations, including security policies, user management, and control of services and devices.
 + Covers techniques for enhancing the physical security of your systems and network.
 + Explains how hackers use information-gathering to find and exploit security flaws.
 + Examines the most effective ways to prevent hackers from gaining root access to a server.
 + Addresses Denial of Service attacks, "malware," and spoofing.
 + Includes appendices covering the TCP/IP protocol stack, well-known ports, and reliable sources for security warnings and updates.


Educators today must be able to respond to the needs of an increasingly diverse student body and to teach all students the knowledge, skills, and attitudes needed for civic participation in a globalized, pluralist society. While state departments of education and national teacher organizations have begun to adopt global awareness in their teaching standards and evaluation tools, educators need to understand what globally competent teachers actually do in classrooms across subject areas and grade levels.  This qualitative, multiple case study explores the signature pedagogies (Shulman, 2005) of 10 in-service teachers in one southeastern state who teach for global competence in math, music, science, English, social studies, and language classes across elementary, middle, and high schools. We found three signature pedagogies that characterized globally competent teaching practices across participants: 1) intentional integration of global topics and multiple perspectives into and across the standard curriculum; 2) ongoing authentic engagement with global issues; and 3) connecting teachers' global experiences, students' global experiences, and the curriculum. These signature pedagogies provide visions of possibility for concrete practices teachers can adapt to infuse global citizenship education into their own contexts and for policies that school districts and teacher education programs can consider in preparing and supporting teachers in this work.


Academic libraries continue to innovate its resources and services to exceed the expectations of its millennial users by reconsidering new trends in management. This is because millennials have varied attitudinal behavior, changing needs and technological skills. Library managers then need to rethink management strategies to address such and eventually to improve library services. One management concept could be the use of McDonaldization in the library. Ritzer (1996) introduced the concept of McDonaldization in his book entitled "The McDonaldization of Society" wherein he argued that the principles of the success of American hamburger chain has a great impact not only in economic patterns but also other facets of the society in general. According to Crossman (2017), McDonaldization is the rationalization of production, work, and consumption. It is characterized by four dimensions namely: efficiency, calculability, predictability and control which have favorable and irreversible changes. On the other hand, Larney (1996) stressed the negative effects which include the ecological impact, dehumanizing effect and quantity over quality in products and services. These effects are not only limited to the fast food industry but also in educational institutions particularly on the information sectors like academic libraries. The increasing pressure for colleges and universities to control costs and maximized efficiency contributed to lessening the independence of faculty, including library staff (Quinn, 2000). However, McDonaldization concept is not a popular management concept among librarians in the Philippines. Thus, the main thrust of this study is to answer the following questions: 1) What is the level of awareness of academic librarians on McDonaldization in academic library; and 2) What is the level of applicability of McDonaldization as a management strategy in the academic library. It made use of quantitative method of research using a researcher-made survey questionnaire and was conducted in the second semester of schoolyear 2017-2018. Data were gathered from 10 professional registered librarians from Saint Mary's University Learning Resource Center, Bayombong, Nueva Vizcaya, Philippines. Descriptive statistics like median was used to describe the data gathered. Interview was also used to further deepen the analysis and interpretation of data. The study found that librarians are highly aware of the concept on McDonaldization and they revealed that it is highly applicable as a management strategy in academic libraries. Interview also revealed that unknowingly McDonaldization had been introduced or practiced in the different aspects of library work using the four dimensions namely efficiency, calculability, predictability and control. The "McDonaldized Library" is heavily attributed to the proliferation and advancement of Communication and Information Technologies. This concept has its own advantages as well as disadvantages such as dehumanizing effect among librarians and quality of library services thus it is recommended that a complete and thorough study on the use of McDonaldization as a management style in academic libraries be explored.


Alaska has made two sweeping reforms to its trust laws in an effort to position itself as the most sophisticated "offshore" trust jurisdiction for wealthy U.S. citizens and non-U.S. persons holding substantial U.S. property or stock. This article describes Alaska's departure from the venerated (if misinterpreted) rule against perpetuities and illustrates how the new Alaska law effectively allows taxpayers to make their own decision about the level at which a trust will be taxed. This article also details Alaska's approach to self-settled spendthrift trusts. In certain circumstances, an existing or future creditor will be prevented from satisfying a claim out of a trust even to the extent of any interest retained by the grantor in the trust. The article concludes by comparing Alaska self-settled trusts to those in other offshore jurisdictions and suggests that Alaska may be the jurisdiction of choice for some taxpayers.


Chagas disease remains the most important parasitic infection in Latin America. The
aetiological agent, Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae), is a complex
vector-borne zoonosis transmitted in the faeces of hematophagous triatomine bugs
(Hemiptera: Reduviidae: Triatominae), and maintained by mammalian reservoir hosts
ranging from the southern United States to Argentinean Patagonia. In the absence of
chemotherapy, infection is life-long and can lead to a spectrum of pathological sequelae
ranging from subclinical to lethal cardiac and/or gastrointestinal complications in up to 30%
of patients.
T. cruzi displays remarkable genetic diversity, which has long been suspected to contribute to
the considerable variation in clinical symptoms observed between endemic regions.
Currently, isolates of T. cruzi can be assigned to a minimum of six stable genetic lineages or
discrete typing units (DTUs) (TcI-TcVI), which are broadly associated with disparate
ecologies, transmission cycles and geographical distributions. The principal mode of
reproduction among T. cruzi strains is the subject of an intense, decades-old debate. Despite
the existence of two recent natural hybrid lineages (TcV and TcVI), which resemble meiotic
F1 progeny, a pervasive view is that recombination has been restrained at an evolutionary
scale and is of little epidemiological relevance to contemporary parasite populations.
The aim of this PhD project was to investigate T. cruzi genetic diversity through significant
development of phylogenetic markers and their application to the characterization of natural
parasite population structures and genetic exchange mechanisms. Multiple, single-copy,
chromosomally-independent, nuclear housekeeping genes were assessed initially for their
ability to allocate isolates to DTU-level, to facilitate higher resolution intra-lineage analyses
and finally for their inclusion alongside additional targets in a standardized T. cruzi
multilocus sequence typing (nMLST) scheme. For the immediate future, nuclear MLST,
using a panel of four to seven nuclear loci, is a robust, reproducible and highly discriminatory
method that has potential to become the new gold standard for T. cruzi DTU assignment.
To investigate natural parasite population structures and uncover evidence of genetic
exchange, a high resolution mitochondrial MLST (mtMLST) scheme, based on ten gene
fragments, was developed and evaluated against current nuclear markers (multilocus
microsatellite typing; MLMT) using isolates belonging to the oldest and most widely
distributed lineage (TcI). Observations of gross nuclear-mitochondrial phylogenetic
incongruence indicate that recombination is ongoing, geographically widespread and
continues to influence natural populations, challenging the traditional paradigm of clonality
in T. cruzi.
Application of this combined nuclear-mitochondrial methodology to intensively sampled,
minimally-subdivided TcI populations revealed extensive mitochondrial introgression within
a disease focus in North-East Colombia as well as among arboreal transmission cycles in
Bolivia. Failure to detect any reciprocal nuclear hybridization among recombinant strains
!
4
may be indicative of alternate, cryptic mating strategies in T. cruzi, which are challenging to
reconcile with both in vitro parasexual mechanisms of genetic exchange described, and
patterns of Mendelian allele inheritance among natural hybrid DTUs.
High resolution genotyping of TcI populations was also undertaken to explore the interaction
between parasite genetic heterogeneity and ecological biodiversity, exposing the significant
impact human activity has had on T. cruzi evolution. Reduced genetic diversity, accelerated
parasite dissemination between densely populated areas and mitochondrial gene flow
between domestic and sylvatic populations, suggests humans may have played a crucial role
in T. cruzi dispersal across the Bolivian highlands. Parallel reductions in genetic diversity
were observed among isolates from the Brazilian Atlantic Forest, attributable to ongoing
anthropogenic habitat fragmentation. By comparison domestic TcI isolates (TcIDOM) are
divergent from their sylvatic counterparts, but also genetically homogeneous, and likely to
have originated in North/Central America before distribution southwards. Molecular dating
of Colombian TcIDOM clones confirmed that this clade emerged 23,000 ± 12,000 years,
coinciding with the earliest human migration into South America.
Lastly, Illumina amplicon deep sequencing markers were developed to explore the interaction
between parasite multiclonality and clinical status of chronic Chagas disease. An
unprecedented level of intra-host genetic diversity was detected, highlighting putative
diversifying selection affecting antigenic surface proteases, which may facilitate survival in
the mammalian host. In lieu of comparative genomics of representative T. cruzi field isolates,
not yet a reality, as is the case with other more experimentally-tractable trypanosomatids,
presented herein are some of the highest resolution genotyping techniques developed in T.
cruzi to date, which have the potential to expand our current understanding of parasite
genetic diversity and its relevance to clinical outcome of Chagas disease.


Larvae of Belonepterygion fasciolatum (in the plesiopid subfamily Acanthoclininae) are described based on two postflexion, pelagic specimens from Espirito Santo, Vanuatu (5.7 mm SL) and Magnetic Island, Great Barrier Reef, Australia (6.3 mm SL), as well as two settled individuals (9.4 and 11.9 mm SL) from One Tree Island, Great Barrier Reef, Australia. Distinct morphological characteristics of acanthoclinins form early in development (c. 6 mm SL), including weak head spination limited to a single opercular spine, a large oblique mouth and three unbranched lateral lines. Dorsal and anal fins have many more spines than soft rays, dorsal and anal fin spines have thickened fleshy pads distally, the body is relatively slender with a deep, short caudal peduncle. Pigmentation consists of melanophores more-or-less evenly distributed across the trunk and head as well as a pale brown background (not obvious melanophores, the colour of skin and muscle) on the body that intensifies with growth. These are the first tropical acanthoclinin larvae to be reported. For reasons that are unclear, larvae of tropical and warm-temperate acanthoclinin species are rare in collections, but cool-temperate acanthoclinin larvae can be abundant.


Xylitol is an alternative sweetener to sucrose, glucose and fructose, and is available under a number of brands in South Africa. Carbon stable isotope values (δ13C) of a selection of commercially available xylitol products (n=28) were analysed and compared with sugar samples (n=29). Sugarcane (C4) and beet sugar (C3) derived sugar samples aligned with published values of source, although two samples that indicated a sugarcane origin suggested a beet sugar origin. Control corn-derived samples defined a stepwise xylose to xylitol discrimination of +0.7‰. The distinction between C3- and C4-derived xylitol was less clear with three samples difficult to define (range = -14.8 to -17.1‰). The values for a suite of xylitol samples (-22.3‰ to -19.7‰; n=8) that aligned closely with a suspected C3-derived xylose, were ~8‰ more positive than known birch isotope values. Some xylitol samples may thus represent (1) a mixture of C3- and C4-derived products, (2) derivation from a CAM species source or (3) different processing techniques in which the discrimination values of xylose from corn, and xylose from birch, may differ because of the respective chemical processing techniques. No samples that claimed a birch bark origin were within the range of samples suggested to be corn derived (i.e. -13.0‰ to -9.7‰, n=16). We suggest that the threshold values provided are relatively robust for defining the origins of xylitol and sugar, and can be used in determining the authenticity and claims of suppliers and producers.


This work investigates the relation between subjective Video Quality Assessment (VQA) metrics and psychophysiological measures of human interaction assessment such as gaze tracking, electroencephalography and facial expression recognition. Subjective quality assessment is based on deliberate judgement attributions of perceived quality and processes that human perceivers are not consciously aware of. Traditional VQA methods ask participants to deliberately assign a quality score to videos in terms of the perceptual video quality. A methodology combining psychophysiological measures with traditional VQA methods is rarely used in the literature. This paper describes a model of video quality assessment which takes into account both explicit and implicit measures of subjective quality, by addressing two questions: (1) Do traditional video quality assessment methods correlate with unaware/implicit psychophysiological measures of quality perception assessment? (2) What can the main psychophysiological methods add to traditional video quality assessment? Findings show that (1) psychophysiological measures are able to measure differences of perceptual quality in compressed videos in terms of number of fixations and that (2) both VQA methods and psychophysiological assessment methods combined are able to provide additional information about cognitive and affective processes of attribution of the affective factors that underlie the attribution of quality.


Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.


[1] The Eastern Equatorial Pacific (EEP) is a high nutrient–low chlorophyll region of the ocean. Downcore nitrogen isotope records from the EEP have been previously interpreted as a direct reflection of changes in nutrient consumption. However, the observed changes in sedimentary δ15N since the last glacial maximum have no coherent relationship with export productivity or an inferred variation in the iron-to-nitrate ratio of the surface waters. Rather, downcore N isotope records in the EEP strongly resemble changes in the extent of water column denitrification as recorded in nearby sedimentary δ15N records along the western margin of the Americas. This similarity is attributed to the overprinting of the N isotopic composition of nitrate in the EEP through the advection of nitrate westward from the margins in the subsurface. A local nitrogen isotope record of changes in the degree of nutrient consumption is extracted from the bulk sedimentary record by subtracting two different sedimentary δ15N records of denitrification changes from two new EEP δ15N records (TR163-22 and ODP Site 1240). The denitrification records used are from 1) the Central American margin (ODP Site 1242) and 2) the South American margin (GeoB7139-2). The degree of consumption in the surface waters declines rapidly from elevated values during the last glacial maximum to a pair of minima around 15 and 11–13 ka, and finally it increases into the Holocene. The derived EEP nitrogen isotope record indicates that the regional peak in export productivity occurred when the supply of nutrients exceeded the apparently high demand. The influx of nutrients during the deglaciation is attributed to the resumption of intense overturning in the Southern Ocean and the release of sequestered CO2 and nutrient-rich, O2 poor waters from the deep ocean. This has important implications for understanding the glacial-interglacial scale variation in intermediate water suboxia and water column denitrification.


Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While antimicrotubule drugs are well-established, antiactin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other antitropomyosin analogues for anticancer and on-target activity using a series of in vitro cell-based and biochemical assays. ATM-3507 was selected as the new lead based on its ability to disable Tpm3.1-containing filaments, its cytotoxicity potency, and more favorable drug-like characteristics. We tested ATM-3507 and TR100 alone and in combination with antimicrotubule agents against neuroblastoma models in vitro and in vivo. Both ATM-3507 and TR100 showed a high degree of synergy in vitro with vinca alkaloid and taxane antimicrotubule agents. In vivo, combination-treated animals bearing human neuroblastoma xenografts treated with antitropomyosin combined with vincristine showed minimal weight loss, a significant and profound regression of tumor growth and improved survival compared with control and either drug alone. Antitropomyosin combined with vincristine resulted in G2–M phase arrest, disruption of mitotic spindle formation, and cellular apoptosis. Our data suggest that small molecules targeting the actin cytoskeleton via tropomyosin sensitize cancer cells to antimicrotubule agents and are tolerated together in vivo. This combination warrants further study. Mol Cancer Ther; 16(8); 1555–65. ©2017 AACR.


Dynamic cell structures (DCS) represent a family of artificial neural architectures suited both for unsupervised and supervised learning. They belong to the recently (Martinetz 1994) introduced class of topology representing networks (TRN) that build perfectly topology preserving feature maps. DCS employ a modified Kohonen learning rule in conjunction with competitive Hebbian learning. The Kohonen type learning rule serves to adjust the synaptic weight vectors while Hebbian learning establishes a dynamic lateral connection structure between the units reflecting the topology of the feature manifold. In case of supervised learning, i.e., function approximation, each neural unit implements a radial basis function, and an additional layer of linear output units adjusts according to a delta-rule. DCS is the first RBF-based approximation scheme attempting to concurrently learn and utilize a perfectly topology preserving map for improved performance. Simulations on a selection of CMU-Benchmarks indicate that the DCS idea applied to the growing cell structure algorithm (Fritzke 1993c) leads to an efficient and elegant algorithm that can beat conventional models on similar tasks.


Access to successful basic adult education is a concern in many countries the world over. In this innovative study, sixteen researchers from ten different countries of the Western and Arab worlds look at adult education, and discuss how an ecological approach to education, focussing on the cultural traditions and natural environments of communities, can be more useful than education in specialized institutions. Education, they argue, is dependent on the transmission of knowledge and know-how within an environment appropriate to the students. This interdisciplinary work is a follow-up to preceding works of research on literacy, published in the ALPHA series in Quebec and at UNESCO over the past twenty years. In their humanist, ecological vision of the world, the contributors aim to provide alternatives to neo-capitalist thinking, and improve lives and justice for all people on earth.


AbstractWe evaluated the results of a large-scale commercial project that illustrated the capabilities of advanced time-domain electromagnetic (TDEM) technologies powered with integrated interpretation of geologic and geophysical data. To study the hydrocarbon prospectivity of a field in Eastern Siberia, we developed a survey design, and then acquired, processed, and interpreted the TDEM data from 30 profiles (total length 772 km) covering an area of approximately 1000  km2. The data were acquired using the conventional TDEM and a novel high-resolution version of TDEM, the focused-source electromagnetic method. We described the geologic framework, data acquisition methodologies, and key results obtained using integrated TDEM, seismic, and well-logging data. The interpretation was used to select well locations for additional exploratory drilling. Postsurvey drilling supported our interpretation. The presented case study demonstrates the value of TDEM in the exploration workflow.


Aluminium oxide thin films were deposited by metal-organic chemical vapor deposition (MOCVD) on stainless steel substrates, (AISI 304). The deposition was studied systematically in a hot-wall CVD reactor (HWR) at atmospheric pressure. The used precursors were aluminium acetylacetonate (Al(acac)3) and synthetic air, which are nontoxic and easy to handle. The phase composition, surface morphology and chemical composition of the films were studied by XRD, SEM and EDX, respectively. The deposition starts at 350°C and the maximum growth rate occurs at a substrate temperature of 475°C. Increasing the furnace temperature beyond 500°C leads to depletion of the precursor and thus the maximum deposition rate is shifted towards the gas inlet. Films deposited at 500°C were transparent and amorphous. They consist mainly of Al and O, although the existence of aluminium hydroxides can not be excluded. Annealing at higher temperatures leads to crystallization and phase transformations: at 800°C γ-Al2O3 films are obtained and at 1115°C α-Al2O3 is formed. The films are stable up to 800°C, at higher temperature they are spalling.
Beta iron disilicide thin films (β-FeSi2) were successfully deposited by low pressure metal-organic chemical vapor deposition (MOCVD) on silicon substrates, Si(100) using ferrocene (Fe(C5H5)2) and TMS (Si(CH3)4) as precursors. These CVD experiments were performed for the first time in a Halogen Lamp CVD Reactor (HLR) designed for this investigation. By this design, a maximum set point temperature of 800°C and any temperature down to room temperature can be easily achieved and controlled. This control allows possible deposition of different films at different deposition temperature within the same experimental run.
Preparation of iron disilicide films by using a direct deposition technique (DDT) and a step deposition technique (SDT) with later annealing were studied. In DDT ferrocene and TMS were supplied into the CVD chamber at the same time. For SDT each precursor was supplied separately in order to deposit an iron film followed by a silicon film, finally the iron silicide is formed in an annealing step. The phase composition, surface morphology and chemical composition of the films were studied by XRD, SEM and EDX, respectively.
Films deposited by DDT at 785-800°C and 30 mbar were transparent, amorphous, and well adhesive. EDX analysis shows that the films consist of silicon and very small amount of iron. The films prepared by SDT were formed from crystalline iron films deposited on the substrate at 700°C and amorphous silicon films deposited on the surface of the iron films at 800°C. Also, iron films and silicon films were deposited separately on silicon and steel substrates respectively before performing the SDT. It was found that the iron films can not be deposited directly from ferrocene because of the presence of high level of carbon in the film. Therefore, the carbon containing films were treated with hydrogen in order to produce pure films. After purification XRD analyses show that the films are crystalline (α-Fe). Amorphous silicon films were deposited at 800°C and 30 mbar. A mixture of iron disilicide phases, FeSi, FeSi2 and β-FeSi2 can be prepared by annealing the SDT deposited films 2 hr at 900-950°C.


For all altimeter missions, precise estimates of geophysical parameters are obtained thanks to an algorithm called "retracking" that fits an analytical model to the measured waveforms. The Brown model provides a good representation of the return echo over deep ocean surfaces and is commonly used. Many different chains can be considered (and have already been tested) for this processing. An unweighted Least Square Estimate derived from a Maximum Likelihood Estimator (MLE) (Dumont 1985; Rodriguez 1988) is implemented in most altimeter ground processing approaches (TOPEX, Jason-1, Jason-2, and Envisat). The aim of this paper is to evaluate the performance of two retracking algorithms based on the same least square principle: The MLE3 algorithm estimates three parameters (range, significant wave height, and power) whereas the MLE4 estimates four parameters (the three previous ones and the slope of the waveform trailing edge). MLE3 was used on Jason-1 before star tracker problems occurred. The MLE4 algorithm has been used for Jason-1 Version B products and onward and for Jason-2 products from the start of the mission. Both algorithms are compared in the paper. Advantages and drawbacks of both algorithms are pointed out showing notable benefits provided by MLE4 especially for waveforms that do not conform to the Brown model.


Cell shape asymmetries and oriented cell divisions shape epithelial tubes during morphogenesis. Epithelial tubes form the basis of many tissues and organs, including the lung, kidney, gut, and heart. Asymmetries with respect to the major body axes are often important in the development and function of such organs, so understanding how epithelial tubes bend and twist is important for elucidating morphogenesis of tube-based structures. Two studies examine the mechanical basis and molecular regulation of epithelial tube size and shape. Tang et al. examined the mechanisms that regulate branch length and circumference in the developing mouse lung, in which tube length increases faster than circumference without changes in cell shape or size. This pattern of allometric growth correlated with a bias in mitotic spindle orientation, with a large portion of the cells dividing parallel to the long axis of the tube. Increasing the activity of extracellular signal–regulated kinases (ERKs) 1 and 2 abrogated allometric growth and eliminated the bias in mitotic spindle orientation. Furthermore, knocking out Sprouty 1 (Spry1) and Spry2, which encode negative regulators of fibroblast growth factor (FGF)–induced ERK signaling, also led to abnormal tube morphology and loss of mitotic spindle orientation bias, suggesting that FGF-mediated activation of ERK signaling was responsible for the observed growth and spindle orientation phenomena. Genetic interaction experiments identified FGF10 as the relevant FGF ligand in this context of lung development. Mathematical modeling revealed that the observed mitotic spindle bias could account for the observed growth dynamics in both normal and ERK-activated contexts. In a related study, Taniguchi et al. explored the mechanism by which the hindgut of the fruit fly rotates to the left to create a rightward bend during development. The authors found that the epithelial cells that make this bend have an inherent polarity that the authors called "planar cell-shape chirality" (PCC) along the left-right (LR) axis prior to the rotation and that PCC was reversed in embryos lacking Myo1D, in which the hindgut rotates to the right rather than to the left. Drosophila E-cadherin (DE-Cad) was also required for proper LR asymmetry of the hindgut and was enriched on the left side of hindgut epithelial cells, and this polarity was also reversed in embryos lacking Myo1D. Because Myo1D and DE-Cad restricted the expansion of cell boundaries, the authors proposed that greater tension on the left side of the hindgut epithelial cells was directly responsible for driving the leftward rotation, a hypothesis that was supported by computational modeling. As discussed in a Perspective by Horne-Badovinac and Munro, these studies illustrate the power of combining computational modeling with in vivo observations and experimentation for elucidating the complex morphogenesis of critical tissues and organs. S. Horne-Badovinac, E. Munro, Tubular transformations. Science 333, 294–295 (2011). [Abstract] [Full Text] N. Tang, W. F. Marshall, M. McMahon, R. J. Metzger, G. R. Martin, Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Science 333, 342–345 (2011). [Abstract] [Full Text] K. Taniguchi, R. Maeda, T. Ando, T. Okumura, N. Nakazawa, R. Hatori, M. Nakamura, S. Hozumi, H. Fujiwara, K. Matsuno, Chirality in planar cell shape contributes to left-right asymmetric epithelial morphogenesis. Science 333, 339–341 (2011). [Abstract] [Full Text]


BACKGROUND AND OBJECTIVES
Immunoglobulin G (IgG) fractions from subjects with antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway. This study investigated the effect that IgG fractions from aPS subjects containing anti-TFPI activity have on in vitro TF-induced thrombin generation.

DESIGN AND METHODS
TFPI and anti-TFPI activities were determined in normal controls (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay based on the generation of factor Xa. Anti-TFPI activity was determined after incubating IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity.

RESULTS
TFPI activity in controls (1.13+/-0.25 U/mL) was significantly lower than in subjects (1.30+/-0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects than controls (p = 0.0001). TF-induced thrombin generation was positively associated with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated in 5 subjects.

INTERPRETATION AND CONCLUSIONS
Anti-TFPI activity was confirmed in 65% of aPS subjects. IgG fractions demonstrated a variable ability to interfere with TFPI function and TF-induced thrombin generation. Cross-reacting antiphospholipid antibodies and/or other entities may interfere with TFPI function, resulting in a net increase in thrombin generation and an increased thrombotic risk.


The antiquarian Joseph Holland (d. 1605) owned a large, but damaged, Chaucerian manuscript from the early fifteenth century (now Cambridge University Library Gg.4.27). Holland recognized in the manuscript an effort to construct a collection based on Chaucerian authorship, and he repaired and added to it using a copy of the 1598 printed edition of Chaucer's collected Works. From this edition, he took not only the text of Chaucer's poems, but paratextual materials as well, including a glossary, biographical information, and a frontispiece. His activities reveal how a distinctly post-medieval understanding of what the collected works of Chaucer should look like shaped the history of this fifteenth-century manuscript, and underscore impact of later stages of transmission can have on the way medieval books are read and preserved.


Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7·8 (sd 2·9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum β-carotene against the lowest tertile was 0·47 (95 % CI 0·23, 0·95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum α- and β-carotene and β-cryptoxanthin (HR 0·66; 95 % CI 0·46, 0·96; HR, 0·54; 95 % CI 0·37, 0·79; and HR 0·66; 95 % CI 0·44, 0·99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects.


Network coding (NC) implemented in passive optical networks (PONs) holds great promise due to the localization trends of emerging applications and services, which occur between the optical network units (ONUs) of the same PON interface. Traffic locality can be provided by inter-ONU flows, such as video-on-demand, peer-to-peer file sharing, and mobile device-to-device communications. Meanwhile, the latest draft standard on PON ¿ service interoperability Ethernet passive optical network (SIEPON) IEEE P1904.1 ¿ provides a means to ensure energy efficiency and quality of service (QoS) in EPON. In this paper, we propose an NC-based SIEPON system (NC-SIEPON) to improve its energy efficiency and network performance. Based on the proposed system structure, an NC-based dynamic hybrid scheduling scheme is designed to efficiently support multiclass QoS. In addition, we combine NC with a power-saving mechanism to maximize the NC efficiency and to minimize the power consumption of the network. By means of simulations, we show that by introducing NC the network performance of the proposed NC-SIEPON in terms of downstream delay, throughput, packet loss ratio, and energy efficiency is improved significantly compared with the original SIEPON.


AIMS
Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1-3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome.

METHODS AND RESULTS
A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1-5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0-8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively.

CONCLUSION
Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.


Abstract. The recent advent of single photon sensitive airborne LiDAR (Light Detection And Ranging) sensors has enabled higher areal coverage performance at the price of an increased outlier rate and a lower ranging accuracy compared to conventional Multi-Photon LiDAR. Single Photon LiDAR, in particular, uses green laser light capable of penetrating clear shallow water. Although primarily designed for large area topographic mapping, the technique can also be used for mapping the water surface and shallow water bathymetry. In this contribution we investigate the capability of Single Photon LiDAR for large area mapping of water surface heights. While interface returns from conventional green-only bathymetric sensors generally suffer from water level underestimation due to the water penetration capabilities of green laser radiation, the specific questions are, if Single Photon LiDAR (i) is less affected by this well known effect due to the high receiver sensitivity and (ii) consequently delivers a higher number of water surface echoes. The topic is addressed empirically in a case study by comparing the water surface responses of Single Photon LiDAR (Navarra, Spain) and Multi-Photon Topo-Bathymetric LiDAR (Neubacher Au, Austria) for selected water bodies with a horizontal water surface (reservoirs, ponds). Although flown at different altitudes, both datasets are well comparable as they exhibit the same strip point density of ca. 14 points/m2. The expected superiority of Single Photon LiDAR over conventional green-only bathymetric LiDAR for mapping water surfaces could not be verified in this investigation. While both datasets show good agreement compared to a reference water level when aggregating points into cells of 10 × 10 m2 (mean deviations < 5 cm), higher resolution Single Photon LiDAR based water surface models (grid size 1–5 m) show a systematic water level underestimation of 5–20 cm. However, independently measured ground truth observations and simultaneous data acquisition of the same area with both techniques are necessary to verify the results.