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.

Three essays on the psychology of investment and financial markets

Préface My thesis consists of three essays where I consider equilibrium asset prices and investment strategies when the market is likely to experience crashes and possibly sharp windfalls. Although each part is written as an independent and self contained article, the papers share a common behavioral approach in representing investors preferences regarding to extremal returns. Investors utility is defined over their relative performance rather than over their final wealth position, a method first proposed by Markowitz (1952b) and by Kahneman and Tversky (1979), that I extend to incorporate preferences over extremal outcomes. With the failure of the traditional expected utility models in reproducing the observed stylized features of financial markets, the Prospect theory of Kahneman and Tversky (1979) offered the first significant alternative to the expected utility paradigm by considering that people focus on gains and losses rather than on final positions. Under this setting, Barberis, Huang, and Santos (2000) and McQueen and Vorkink (2004) were able to build a representative agent optimization model which solution reproduced some of the observed risk premium and excess volatility. The research in behavioral finance is relatively new and its potential still to explore. The three essays composing my thesis propose to use and extend this setting to study investors behavior and investment strategies in a market where crashes and sharp windfalls are likely to occur. In the first paper, the preferences of a representative agent, relative to time varying positive and negative extremal thresholds are modelled and estimated. A new utility function that conciliates between expected utility maximization and tail-related performance measures is proposed. The model estimation shows that the representative agent preferences reveals a significant level of crash aversion and lottery-pursuit. Assuming a single risky asset economy the proposed specification is able to reproduce some of the distributional features exhibited by financial return series. The second part proposes and illustrates a preference-based asset allocation model taking into account investors crash aversion. Using the skewed t distribution, optimal allocations are characterized as a resulting tradeoff between the distribution four moments. The specification highlights the preference for odd moments and the aversion for even moments. Qualitatively, optimal portfolios are analyzed in terms of firm characteristics and in a setting that reflects real-time asset allocation, a systematic over-performance is obtained compared to the aggregate stock market. Finally, in my third article, dynamic option-based investment strategies are derived and illustrated for investors presenting downside loss aversion. The problem is solved in closed form when the stock market exhibits stochastic volatility and jumps. The specification of downside loss averse utility functions allows corresponding terminal wealth profiles to be expressed as options on the stochastic discount factor contingent on the loss aversion level. Therefore dynamic strategies reduce to the replicating portfolio using exchange traded and well selected options, and the risky stock.

How family caregivers' medical and moral assumptions influence decision making for patients in the vegetative state: a qualitative interview study.

Background Decisions on limiting life-sustaining treatment for patients in the vegetative state (VS) are emotionally and morally challenging. In Germany, doctors have to discuss, together with the legal surrogate (often a family member), whether the proposed treatment is in accordance with the patient's will. However, it is unknown whether family members of the patient in the VS actually base their decisions on the patient's wishes. Objective To examine the role of advance directives, orally expressed wishes, or the presumed will of patients in a VS for family caregivers' decisions on life-sustaining treatment. Methods and sample A qualitative interview study with 14 next of kin of patients in a VS in a long-term care setting was conducted; 13 participants were the patient's legal surrogates. Interviews were analysed according to qualitative content analysis. Results The majority of family caregivers said that they were aware of aforementioned wishes of the patient that could be applied to the VS condition, but did not base their decisions primarily on these wishes. They gave three reasons for this: (a) the expectation of clinical improvement, (b) the caregivers' definition of life-sustaining treatments and (c) the moral obligation not to harm the patient. If the patient's wishes were not known or not revealed, the caregivers interpreted a will to live into the patient's survival and non-verbal behaviour. Conclusions Whether or not prior treatment wishes of patients in a VS are respected depends on their applicability, and also on the medical assumptions and moral attitudes of the surrogates. We recommend repeated communication, support for the caregivers and advance care planning.

A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.

PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN: Experimental study. PARTICIPANTS: Four affected and 6 nonaffected family members. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15. MAIN OUTCOME MEASURES: Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein. CONCLUSIONS: In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

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.

Climate-based empirical models show biased predictions of butterfly communities along environmental gradients

A better understanding of the factors that mould ecological community structure is required to accurately predict community composition and to anticipate threats to ecosystems due to global changes. We tested how well stacked climate-based species distribution models (S-SDMs) could predict butterfly communities in a mountain region. It has been suggested that climate is the main force driving butterfly distribution and community structure in mountain environments, and that, as a consequence, climate-based S-SDMs should yield unbiased predictions. In contrast to this expectation, at lower altitudes, climate-based S-SDMs overpredicted butterfly species richness at sites with low plant species richness and underpredicted species richness at sites with high plant species richness. According to two indices of composition accuracy, the Sorensen index and a matching coefficient considering both absences and presences, S-SDMs were more accurate in plant-rich grasslands. Butterflies display strong and often specialised trophic interactions with plants. At lower altitudes, where land use is more intense, considering climate alone without accounting for land use influences on grassland plant richness leads to erroneous predictions of butterfly presences and absences. In contrast, at higher altitudes, where climate is the main force filtering communities, there were fewer differences between observed and predicted butterfly richness. At high altitudes, even if stochastic processes decrease the accuracy of predictions of presence, climate-based S-SDMs are able to better filter out butterfly species that are unable to cope with severe climatic conditions, providing more accurate predictions of absences. Our results suggest that predictions should account for plants in disturbed habitats at lower altitudes but that stochastic processes and heterogeneity at high altitudes may limit prediction success of climate-based S-SDMs.

Unconditioned responses and functional fear networks in human classical conditioning.

Human imaging studies examining fear conditioning have mainly focused on the neural responses to conditioned cues. In contrast, the neural basis of the unconditioned response and the mechanisms by which fear modulates inter-regional functional coupling have received limited attention. We examined the neural responses to an unconditioned stimulus using a partial-reinforcement fear conditioning paradigm and functional MRI. The analysis focused on: (1) the effects of an unconditioned stimulus (an electric shock) that was either expected and actually delivered, or expected but not delivered, and (2) on how related brain activity changed across conditioning trials, and (3) how shock expectation influenced inter-regional coupling within the fear network. We found that: (1) the delivery of the shock engaged the red nucleus, amygdale, dorsal striatum, insula, somatosensory and cingulate cortices, (2) when the shock was expected but not delivered, only the red nucleus, the anterior insular and dorsal anterior cingulate cortices showed activity increases that were sustained across trials, and (3) psycho-physiological interaction analysis demonstrated that fear led to increased red nucleus coupling to insula but decreased hippocampus coupling to the red nucleus, thalamus and cerebellum. The hippocampus and the anterior insula may serve as hubs facilitating the switch between engagement of a defensive immediate fear network and a resting network.

Application of a roughness-length representation to parameterize energy loss in 3-D numerical simulations of large rivers

Recent technological advances in remote sensing have enabled investigation of the morphodynamics and hydrodynamics of large rivers. However, measuring topography and flow in these very large rivers is time consuming and thus often constrains the spatial resolution and reach-length scales that can be monitored. Similar constraints exist for computational fluid dynamics (CFD) studies of large rivers, requiring maximization of mesh-or grid-cell dimensions and implying a reduction in the representation of bedform-roughness elements that are of the order of a model grid cell or less, even if they are represented in available topographic data. These ``subgrid'' elements must be parameterized, and this paper applies and considers the impact of roughness-length treatments that include the effect of bed roughness due to ``unmeasured'' topography. CFD predictions were found to be sensitive to the roughness-length specification. Model optimization was based on acoustic Doppler current profiler measurements and estimates of the water surface slope for a variety of roughness lengths. This proved difficult as the metrics used to assess optimal model performance diverged due to the effects of large bedforms that are not well parameterized in roughness-length treatments. However, the general spatial flow patterns are effectively predicted by the model. Changes in roughness length were shown to have a major impact upon flow routing at the channel scale. The results also indicate an absence of secondary flow circulation cells in the reached studied, and suggest simpler two-dimensional models may have great utility in the investigation of flow within large rivers. Citation: Sandbach, S. D. et al. (2012), Application of a roughness-length representation to parameterize energy loss in 3-D numerical simulations of large rivers, Water Resour. Res., 48, W12501, doi: 10.1029/2011WR011284.

Multivariate QST-FST comparisons: a neutrality test for the evolution of the g matrix in structured populations.

Neutrality tests in quantitative genetics provide a statistical framework for the detection of selection on polygenic traits in wild populations. However, the existing method based on comparisons of divergence at neutral markers and quantitative traits (Q(st)-F(st)) suffers from several limitations that hinder a clear interpretation of the results with typical empirical designs. In this article, we propose a multivariate extension of this neutrality test based on empirical estimates of the among-populations (D) and within-populations (G) covariance matrices by MANOVA. A simple pattern is expected under neutrality: D = 2F(st)/(1 - F(st))G, so that neutrality implies both proportionality of the two matrices and a specific value of the proportionality coefficient. This pattern is tested using Flury's framework for matrix comparison [common principal-component (CPC) analysis], a well-known tool in G matrix evolution studies. We show the importance of using a Bartlett adjustment of the test for the small sample sizes typically found in empirical studies. We propose a dual test: (i) that the proportionality coefficient is not different from its neutral expectation [2F(st)/(1 - F(st))] and (ii) that the MANOVA estimates of mean square matrices between and among populations are proportional. These two tests combined provide a more stringent test for neutrality than the classic Q(st)-F(st) comparison and avoid several statistical problems. Extensive simulations of realistic empirical designs suggest that these tests correctly detect the expected pattern under neutrality and have enough power to efficiently detect mild to strong selection (homogeneous, heterogeneous, or mixed) when it is occurring on a set of traits. This method also provides a rigorous and quantitative framework for disentangling the effects of different selection regimes and of drift on the evolution of the G matrix. We discuss practical requirements for the proper application of our test in empirical studies and potential extensions.

The Politics of Network Governance in Europe: The Case of Energy Regulation

Networks are considered increasingly important for policy-making. The literature on new modes of governance in Europe suggests that their horizontal coordination capacity and flexible and informal structures are particularly suitable for governing the multilevel architecture of the European polity. However, empirical evidence about the effects of networks on policy-making and public policies is still quite limited. This article uses the case of the European network of energy regulators to explore the determinants of the position of network members and, in turn, the domestic adoption of soft rules developed within this network. The empirical analysis, based on multivariate statistics and semi-directive interviews, supports the expectation that institutional complementarities increase actors' centrality in networks, while arguments based on organisational resources and age are disproved. Furthermore, results show that the overall level of adoption is considerable and that centrality might have a small positive effect on domestic adoption.

Turner syndrome: evaluation of prenatal diagnosis in 19 European registries.

This study evaluated the prenatal diagnosis of Turner syndrome by ultrasound examination in an unselected population from all over Europe. Data from 19 congenital malformation registries from 11 European countries were analyzed. Turner syndrome was diagnosed in 125 cases (7.2%) in a total of 1,738 chromosome abnormalities. Sixty-seven percent of cases were detected prenatally by ultrasound examination due to the presence of congenital defects. The most frequent anomalies were cystic hygroma (59.5%) and hydrops fetalis (19%). The most frequent karyotype was 45,X (81.6%) followed by different types of mosaicism (16.8%). Significant differences in congenital defects (P = 0.0003) were observed between 45,X karyotypes and 45,X mosaicism cases. Prenatal counseling for 45,X mosaicism should take into account the expectation of a milder phenotype. In 78.6% of cases diagnosed by ultrasound examination due to congenital anomalies, the pregnancy was terminated. Prenatal detection of Turner syndrome by ultrasound examination was high in this unselected population.

Reptiles produce pheomelanin : evidence in the Eastern Hermann's tortoise (Eurotestudo boettgeri)

Reptiles, supposedly, do not produce pheomelanin pigments. Because this claim is based on rather weak evidence, we measured the shell pheomelanin content in the Hermann's Tortoise (Eurotestudo boettgeri). In contrast to expectation, we detected a substantial amount of this pigment. Given the recent interest in the adaptive function of melanin-based color traits, our study opens new avenues of research in reptiles.

Fitness, inclusive fitness, and optimization

Individual-as-maximizing agent analogies result in a simple understanding of the functioning of the biological world. Identifying the conditions under which individuals can be regarded as fitness maximizing agents is thus of considerable interest to biologists. Here, we compare different concepts of fitness maximization, and discuss within a single framework the relationship between Hamilton's (J Theor Biol 7: 1-16, 1964) model of social interactions, Grafen's (J Evol Biol 20: 1243-1254, 2007a) formal Darwinism project, and the idea of evolutionary stable strategies. We distinguish cases where phenotypic effects are additive separable or not, the latter not being covered by Grafen's analysis. In both cases it is possible to define a maximand, in the form of an objective function phi(z), whose argument is the phenotype of an individual and whose derivative is proportional to Hamilton's inclusive fitness effect. However, this maximand can be identified with the expression for fecundity or fitness only in the case of additive separable phenotypic effects, making individual-as-maximizing agent analogies unattractive (although formally correct) under general situations of social interactions. We also feel that there is an inconsistency in Grafen's characterization of the solution of his maximization program by use of inclusive fitness arguments. His results are in conflict with those on evolutionary stable strategies obtained by applying inclusive fitness theory, and can be repaired only by changing the definition of the problem.

Capitalism in the classroom : the impact of self-enhancement values and normative assessment on student motivation, goals and attitudes towards cheating

Abstract The neo-liberal capitalist ideology has come under heavy fire with anecdotal evidence indicating a link between these same values and unethical behavior. Academic institutions reflect social values and act as socializing agents for the young. Can this explain the high and increasing rates of cheating that currently prevail in education? Our first chapter examines the question of whether self-enhancement values of power and açhievement, the individual level equivalent of neo-liberal capitalist values, predict positive attitudes towards cheating. Furthermore, we explore the mediating role of motivational factors. Results of four studies reveal that self-enhancement value endorsement predicts the adoption of performance-approach goals, a relationship mediated by introjected regulation, namely desire for social approval and that self-enhancement value endorsement also predicts the condoning of cheating, a relationship mediated by performance-approach goal adoption. However, self-transcendence values prescribed by a normatively salient source have the potential to reduce the link between self-enhancement value endorsément and attitudes towards cheating. Normative assessment constitutes a key tool used by academic institutions to socialize young people to accept the competitive, meritocratic nature of a sociéty driven by a neo-liberal capitalist ideology. As such, the manifest function of grades is to motivate students to work hard and to buy into the competing ethos. Does normative assessment fulfill these functions? Our second chapter explores the reward-intrinsic motivation question in the context of grading, arguably a high-stakes reward. In two experiments, the relative capacity of graded high performance as compared to the task autonomy experienced in an ungraded task to predict post-task intrinsic motivation is assessed. Results show that whilst the graded task performance predicts post-task appreciation, it fails to predict ongoing motivation. However, perceived autonomy experienced in non-graded condition, predicts both post-task appreciation and ongoing motivation. Our third chapter asks whether normative assessment inspires the spirit of competition in students. Results of three experimental studies reveal that expectation of a grade for a task, compared to no grade, induces greater adoption of performance-avoidance, but not performance-approach, goals. Experiment 3 provides an explanatory mechanism for this, showing that reduced autonomous motivation experienced in previous graded tasks mediates the relationship between grading and adoption of performance avoidance goals in a subsequent task. The above results, when combined, provide evidence as to the deleterious effects of self enhancement values and the associated practice of normative assessment in school on student motivation, goals and ethics. We conclude by using value and motivation theory to explore solutions to this problem.

What Was I Thinking? Eye-Tracking Experiments Underscore the Bias that Architecture Exerts on Nuclear Grading in Prostate Cancer.

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion, selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.