Restriction site-associated DNA sequencing, genotyping error estimation and de novo assembly optimization for population genetic inference.

Restriction site-associated DNA sequencing (RADseq) provides researchers with the ability to record genetic polymorphism across thousands of loci for nonmodel organisms, potentially revolutionizing the field of molecular ecology. However, as with other genotyping methods, RADseq is prone to a number of sources of error that may have consequential effects for population genetic inferences, and these have received only limited attention in terms of the estimation and reporting of genotyping error rates. Here we use individual sample replicates, under the expectation of identical genotypes, to quantify genotyping error in the absence of a reference genome. We then use sample replicates to (i) optimize de novo assembly parameters within the program Stacks, by minimizing error and maximizing the retrieval of informative loci; and (ii) quantify error rates for loci, alleles and single-nucleotide polymorphisms. As an empirical example, we use a double-digest RAD data set of a nonmodel plant species, Berberis alpina, collected from high-altitude mountains in Mexico.

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy.

PURPOSE: To study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. METHODS: Eight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. RESULTS: The distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. CONCLUSION: Decrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

Stochastic time-concentration activity models for cytotoxicity in 3D brain cell cultures.

BACKGROUND: In vitro aggregating brain cell cultures containing all types of brain cells have been shown to be useful for neurotoxicological investigations. The cultures are used for the detection of nervous system-specific effects of compounds by measuring multiple endpoints, including changes in enzyme activities. Concentration-dependent neurotoxicity is determined at several time points. METHODS: A Markov model was set up to describe the dynamics of brain cell populations exposed to potentially neurotoxic compounds. Brain cells were assumed to be either in a healthy or stressed state, with only stressed cells being susceptible to cell death. Cells may have switched between these states or died with concentration-dependent transition rates. Since cell numbers were not directly measurable, intracellular lactate dehydrogenase (LDH) activity was used as a surrogate. Assuming that changes in cell numbers are proportional to changes in intracellular LDH activity, stochastic enzyme activity models were derived. Maximum likelihood and least squares regression techniques were applied for estimation of the transition rates. Likelihood ratio tests were performed to test hypotheses about the transition rates. Simulation studies were used to investigate the performance of the transition rate estimators and to analyze the error rates of the likelihood ratio tests. The stochastic time-concentration activity model was applied to intracellular LDH activity measurements after 7 and 14 days of continuous exposure to propofol. The model describes transitions from healthy to stressed cells and from stressed cells to death. RESULTS: The model predicted that propofol would affect stressed cells more than healthy cells. Increasing propofol concentration from 10 to 100 μM reduced the mean waiting time for transition to the stressed state by 50%, from 14 to 7 days, whereas the mean duration to cellular death reduced more dramatically from 2.7 days to 6.5 hours. CONCLUSION: The proposed stochastic modeling approach can be used to discriminate between different biological hypotheses regarding the effect of a compound on the transition rates. The effects of different compounds on the transition rate estimates can be quantitatively compared. Data can be extrapolated at late measurement time points to investigate whether costs and time-consuming long-term experiments could possibly be eliminated.

Growth in a Cross-Section of Cities: Location, Increasing Returns or Random Growth?

This article analyzes empirically the main existing theories on income and population city growth: increasing returns to scale, locational fundamentals and random growth. To do this we implement a threshold nonlinearity test that extends standard linear growth regression models to a dataset on urban, climatological and macroeconomic variables on 1,175 U.S. cities. Our analysis reveals the existence of increasing returns when per-capita income levels are beyond $19; 264. Despite this, income growth is mostly explained by social and locational fundamentals. Population growth also exhibits two distinct equilibria determined by a threshold value of 116,300 inhabitants beyond which city population grows at a higher rate. Income and population growth do not go hand in hand, implying an optimal level of population beyond which income growth stagnates or deteriorates

Nonclassical measurement error with applications to labor and development issues

Zero correlation between measurement error and model error has been assumed in existing panel data models dealing specifically with measurement error. We extend this literature and propose a simple model where one regressor is mismeasured, allowing the measurement error to correlate with model error. Zero correlation between measurement error and model error is a special case in our model where correlated measurement error equals zero. We ask two research questions. First, we wonder if the correlated measurement error can be identified in the context of panel data. Second, we wonder if classical instrumental variables in panel data need to be adjusted when correlation between measurement error and model error cannot be ignored. Under some regularity conditions the answer is yes to both questions. We then propose a two-step estimation corresponding to the two questions. The first step estimates correlated measurement error from a reverse regression; and the second step estimates usual coefficients of interest using adjusted instruments.

Multisensory mechanisms in temporo-parietal cortex support self-location and first-person perspective.

Self-consciousness has mostly been approached by philosophical enquiry and not by empirical neuroscientific study, leading to an overabundance of diverging theories and an absence of data-driven theories. Using robotic technology, we achieved specific bodily conflicts and induced predictable changes in a fundamental aspect of self-consciousness by altering where healthy subjects experienced themselves to be (self-location). Functional magnetic resonance imaging revealed that temporo-parietal junction (TPJ) activity reflected experimental changes in self-location that also depended on the first-person perspective due to visuo-tactile and visuo-vestibular conflicts. Moreover, in a large lesion analysis study of neurological patients with a well-defined state of abnormal self-location, brain damage was also localized at TPJ, providing causal evidence that TPJ encodes self-location. Our findings reveal that multisensory integration at the TPJ reflects one of the most fundamental subjective feelings of humans: the feeling of being an entity localized at a position in space and perceiving the world from this position and perspective.

Multi-stage oligopoly models with nested logit demand structures: A simplifying approach

Solving multi-stage oligopoly models by backward induction can easily become a com- plex task when rms are multi-product and demands are derived from a nested logit frame- work. This paper shows that under the assumption that within-segment rm shares are equal across segments, the analytical expression for equilibrium pro ts can be substantially simpli ed. The size of the error arising when this condition does not hold perfectly is also computed. Through numerical examples, it is shown that the error is rather small in general. Therefore, using this assumption allows to gain analytical tractability in a class of models that has been used to approach relevant policy questions, such as for example rm entry in an industry or the relation between competition and location. The simplifying approach proposed in this paper is aimed at helping improving these type of models for reaching more accurate recommendations.

Quantificació de l'error comès pels models de níxol ecològic al predir la distribució d'especies generalistes

Report for the scientific sojourn carried out at the University of California at Berkeley, from September to December 2007. Environmental niche modelling (ENM) techniques are powerful tools to predict species potential distributions. In the last ten years, a plethora of novel methodological approaches and modelling techniques have been developed. During three months, I stayed at the University of California, Berkeley, working under the supervision of Dr. David R. Vieites. The aim of our work was to quantify the error committed by these techniques, but also to test how an increase in the sample size affects the resultant predictions. Using MaxEnt software we generated distribution predictive maps, from different sample sizes, of the Eurasian quail (Coturnix coturnix) in the Iberian Peninsula. The quail is a generalist species from a climatic point of view, but an habitat specialist. The resultant distribution maps were compared with the real distribution of the species. This distribution was obtained from recent bird atlases from Spain and Portugal. Results show that ENM techniques can have important errors when predicting the species distribution of generalist species. Moreover, an increase of sample size is not necessary related with a better performance of the models. We conclude that a deep knowledge of the species’ biology and the variables affecting their distribution is crucial for an optimal modelling. The lack of this knowledge can induce to wrong conclusions.

On [summation of 1 raised to the power 1] equivalence relations over the natural numbers

"Vegeu el resum a l'inici del document del fitxer adjunt"

What underlies localization and urbanization economies? Evidence from the location of new firms

The objective of this paper is to analyze why firms in some industries locate in specialized economic environments (localization economies) while those in other industries prefer large city locations (urbanization economies). To this end, we examine the location decisions of new manufacturing firms in Spain at the city level and for narrowly defined industries (three-digit level). First, we estimate firm location models to obtain estimates that reflect the importance of localization and urbanization economies in each industry. In a second step, we regress these estimates on industry characteristics that are related to the potential importance of three agglomeration theories, namely, labor market pooling, input sharing and knowledge spillovers. Localization effects are low and urbanization effects are high in knowledge-intensive industries, suggesting that firms (partly) locate in large cities to reap the benefits of inter-industry knowledge spillovers. We also find that localization effects are high in industries that employ workers whose skills are more industry-specific, suggesting that industries (partly) locate in specialized economic environments to share a common pool of specialized workers.

Error estimate and control in the MSFV method for multiphase flow in porous media

n this paper the iterative MSFV method is extended to include the sequential implicit simulation of time dependent problems involving the solution of a system of pressure-saturation equations. To control numerical errors in simulation results, an error estimate, based on the residual of the MSFV approximate pressure field, is introduced. In the initial time steps in simulation iterations are employed until a specified accuracy in pressure is achieved. This initial solution is then used to improve the localization assumption at later time steps. Additional iterations in pressure solution are employed only when the pressure residual becomes larger than a specified threshold value. Efficiency of the strategy and the error control criteria are numerically investigated. This paper also shows that it is possible to derive an a-priori estimate and control based on the allowed pressure-equation residual to guarantee the desired accuracy in saturation calculation.

Report of the National Taskforce on Obesity: Obesity - the policy challenges: Executive Summary

The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

Obesity - the policy challenges: The report of the National Taskforce on Obesity

Click here to download PDF The prevalence of overweight and obesity has increased with alarming speed over the past twenty years. It has recently been described by the World Health Organisation as a ‘global epidemic’. In the year 2000 more than 300 million people worldwide were obese and it is now projected that by 2025 up to half the population of the United States will be obese if current trends are maintained. The disease is now a major public health problem throughout Europe. In Ireland at the present time 39% of adults are overweight and 18% are obese. Of these, slightly more men than women are obese and there is a higher incidence of the disease in lower socio-economic groups. Most worrying of all is the fact that childhood obesity has reached epidemic proportions in Europe, with body weight now the most prevalent childhood disease. While currently there are no agreed criteria or standards for assessing Irish children for obesity some studies are indicating that the numbers of children who are significantly overweight have trebled over the past decade. Extrapolation from authoritative UK data suggests that these numbers could now amount to more than 300,000 overweight and obese children on the island of Ireland and they are probably rising at a rate of over 10,000 per year. A balance of food intake and physical activity is necessary for a healthy weight. The foods we individually consume and our participation in physical activity are the result of a complex supply and production system. The growing research evidence that energy dense foods promote obesity is impressive and convincing. These are the foods that are high in fat, sugar and starch. Of these potentially the most significant promoter of weight gain is fat and foods from the top shelf of the food pyramid including spreads (butter and margarine), cakes and biscuits, and confectionery, when combined are the greatest contributors to fat intake in the Irish diet. In company with their adult counterparts Irish children are also consuming large amounts of energy dense foods outside the home. A recent survey revealed that slightly over half of these children ate sweets at least once a day and roughly a third of them had fizzy drinks and crisps with the same regularity. Sugar sweetened carbonated drinks are thought to contribute to obesity and for this reason the World Health Organisation has expressed serious concerns at the high and increasing consumption of these drinks by children. Physical activity is an important determinant of body weight. Over recent decades there has been a marked decline in demanding physical work and this has been accompanied by more sedentary lifestyles generally and reduced leisure-time activity. These observable changes, which are supported by data from most European countries and the United States, suggest that physical inactivity has made a significant impact on the increase in overweight and obesity being seen today. It is now widely accepted that adults shoud be involved in 45-60 minutes, and children should be involved in at least 60 minutes per day of moderate physical activity in order to prevent excess weight gain. Being overweight today not only signals increased risk of medical problems but also exposes people to serious psychosocial problems due mainly to widespread prejudice against fat people. Prejudice against obese people seems to border on the socially acceptable in Ireland. It crops up consistently in surveys covering groups such as employers, teachers, medical and healthcare personnel, and the media. It occurs among adolescents and children, even very young children. Because obesity is associated with premature death, excessive morbidity and serious psychosocial problems the damage it causes to the welfare of citizens is extremely serious and for this reason government intervention is necessary and warranted. In economic terms, a figure of approximately â,¬30million has been estimated for in-patient costs alone in 2003 for a number of Irish hospitals. This year about 2,000 premature deaths in Ireland will be attributed to obesity and the numbers are growing relentlessly. Diseases which proportionally more obese people suffer from than the general population include hypertension, type 2 diabetes, angina, heart attack and osteoarthritis. There are indirect costs also such as days lost to the workplace due to illness arising from obesity and output foregone as a result of premature death. Using the accepted EU environmental cost benefit method, these deaths alone may be costing the state as much as â,¬4bn per year. The social determinants of physical activity include factors such as socio-economic status, education level, gender, family and peer group influences as well as individual perceptions of the benefits of physical activity. The environmental determinants include geographic location, time of year, and proximity of facilities such as open spaces, parks and safe recreational areas generally. The environmental factors have not yet been as well studied as the social ones and this research gap needs to be addressed. Clearly there is a public health imperative to ensure that relevant environmental policies maximise opportunities for active transport, recreational physical activity and total physical activity. It is clear that concerted policy initiatives must be put in place if the predominantly negative findings of research regarding the determinants of food consumption and physical activity are to be accepted, and they must surely be accepted by government if the rapid increase in the incidence of obesity with all its negative consequences for citizens is to be reversed. So far actions surrounding nutrition policies have concentrated mostly on actions that are within the remit of the Department of Health and Children such as implementing the dietary guidelines. These are important but government must now look at the totality of policies that influence the type and supply of food that its citizens eat and the range and quality of opportunities that are available to citizens to engage in physical activity. This implies a fundamental examination of existing agricultural, industrial, economic and other policies and a determination to change them if they do not enable people to eat healthily and partake in physical activity. The current crisis in obesity prevalence requires a population health approach for adults and children in addition to effective weight-reduction management for individuals who are severely overweight. This entails addressing the obesogenic environment where people live, creating conditions over time which lead to healthier eating and more active living, and protecting people from the widespread availability of unhealthy food and beverage options in addition to sedentary activities that take up all of their leisure time. People of course have a fundamental right to choose to eat what they want and to be as active as they wish. That is not the issue. What the National Taskforce on Obesity has had to take account of is that many forces are actively impeding change for those well aware of the potential health and well-being consequences to themselves of overweight and obesity. The Taskforce’s social change strategy is to give people meaningful choice. Choice, or the capacity to change (because the strategy is all about change), is facilitated through the development of personal skills and preferences, through supportive and participative environments at work, at school and in the local community, and through a dedicated and clearly communicated public health strategy. High-level cabinet support will be necessary to implement the Taskforce’s recommendations. The approach to implementation must be characterised by joined-up thinking, real practical engagement by the public and private sectors, the avoidance of duplication of effort or crosspurpose approaches, and the harnessing of existing strategies and agencies. The range of government departments with roles to play is considerable. The Taskforce outlines the different contributions that each relevant department can make in driving its strategy forward. It also emphasises its requirement that all phases of the national strategy for healthy eating and physical activity are closely monitored, analysed and evaluated. The vision of the Taskforce is expressed as: An Irish society that enables people through health promotion, prevention and care to achieve and maintain healthy eating and active living throughout their lifespan. Its high-level goals are expressed as follows: Its recommendations, over eighty in all, relate to actions across six broad sectors: high-level government; education; social and community; health; food, commodities, production and supply; and the physical environment. In developing its recommendations the Taskforce has taken account of the complex, multisectoral and multi-faceted determinants of diet and physical activity. This strategy poses challenges for government, within individual departments, inter-departmentally and in developing partnerships with the commercial sector. Equally it challenges the commercial sector to work in partnership with government. The framework required for such initiative has at its core the rights and benefits of the individual. Health promotion is fundamentally about empowerment, whether at the individual, the community or the policy level.

Combining probabilistic land-use change and tree population dynamics modelling to simulate responses in mountain forests

Altitudinal tree lines are mainly constrained by temperature, but can also be influenced by factors such as human activity, particularly in the European Alps, where centuries of agricultural use have affected the tree-line. Over the last decades this trend has been reversed due to changing agricultural practices and land-abandonment. We aimed to combine a statistical land-abandonment model with a forest dynamics model, to take into account the combined effects of climate and human land-use on the Alpine tree-line in Switzerland. Land-abandonment probability was expressed by a logistic regression function of degree-day sum, distance from forest edge, soil stoniness, slope, proportion of employees in the secondary and tertiary sectors, proportion of commuters and proportion of full-time farms. This was implemented in the TreeMig spatio-temporal forest model. Distance from forest edge and degree-day sum vary through feed-back from the dynamics part of TreeMig and climate change scenarios, while the other variables remain constant for each grid cell over time. The new model, TreeMig-LAb, was tested on theoretical landscapes, where the variables in the land-abandonment model were varied one by one. This confirmed the strong influence of distance from forest and slope on the abandonment probability. Degree-day sum has a more complex role, with opposite influences on land-abandonment and forest growth. TreeMig-LAb was also applied to a case study area in the Upper Engadine (Swiss Alps), along with a model where abandonment probability was a constant. Two scenarios were used: natural succession only (100% probability) and a probability of abandonment based on past transition proportions in that area (2.1% per decade). The former showed new forest growing in all but the highest-altitude locations. The latter was more realistic as to numbers of newly forested cells, but their location was random and the resulting landscape heterogeneous. Using the logistic regression model gave results consistent with observed patterns of land-abandonment: existing forests expanded and gaps closed, leading to an increasingly homogeneous landscape.