A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Time Variation in an Optimal Asymmetric Preference Monetary Policy Model

This paper considers a time varying parameter extension of the Ruge-Murcia (2003, 2004) model to explore whether some of the variation in parameter estimates seen in the literature could arise from this source. A time varying value for the unemployment volatility parameter can be motivated through several means including variation in the slope of the Phillips curve or variation in the preferences of the monetary authority.We show that allowing time variation for the coefficient on the unemployment volatility parameter improves the model fit and it helps to provide an explanation of inflation bias based on asymmetric central banker preferences, which is consistent across subsamples.

Essays in revealed preference theory and behavioral economics

Time, risk, and attention are all integral to economic decision making. The aim of this work is to understand those key components of decision making using a variety of approaches: providing axiomatic characterizations to investigate time discounting, generating measures of visual attention to infer consumers' intentions, and examining data from unique field settings.

Chapter 2, co-authored with Federico Echenique and Kota Saito, presents the first revealed-preference characterizations of exponentially-discounted utility model and its generalizations. My characterizations provide non-parametric revealed-preference tests. I apply the tests to data from a recent experiment, and find that the axiomatization delivers new insights on a dataset that had been analyzed by traditional parametric methods.

Chapter 3, co-authored with Min Jeong Kang and Colin Camerer, investigates whether "pre-choice" measures of visual attention improve in prediction of consumers' purchase intentions. We measure participants' visual attention using eyetracking or mousetracking while they make hypothetical as well as real purchase decisions. I find that different patterns of visual attention are associated with hypothetical and real decisions. I then demonstrate that including information on visual attention improves prediction of purchase decisions when attention is measured with mousetracking.

Chapter 4 investigates individuals' attitudes towards risk in a high-stakes environment using data from a TV game show, Jeopardy!. I first quantify players' subjective beliefs about answering questions correctly. Using those beliefs in estimation, I find that the representative player is risk averse. I then find that trailing players tend to wager more than "folk" strategies that are known among the community of contestants and fans, and this tendency is related to their confidence. I also find gender differences: male players take more risk than female players, and even more so when they are competing against two other male players.

Chapter 5, co-authored with Colin Camerer, investigates the dynamics of the favorite-longshot bias (FLB) using data on horse race betting from an online exchange that allows bettors to trade "in-play." I find that probabilistic forecasts implied by market prices before start of the races are well-calibrated, but the degree of FLB increases significantly as the events approach toward the end.

Self-Organized Criticality, Plasticity and Sensorimotor Coupling. Explorations with a Neurorobotic Model in a Behavioural Preference Task

During the last two decades, analysis of 1/f noise in cognitive science has led to a considerable progress in the way we understand the organization of our mental life. However, there is still a lack of specific models providing explanations of how 1/f noise is generated in coupled brain-body-environment systems, since existing models and experiments typically target either externally observable behaviour or isolated neuronal systems but do not address the interplay between neuronal mechanisms and sensorimotor dynamics. We present a conceptual model of a minimal neurorobotic agent solving a behavioural task that makes it possible to relate mechanistic (neurodynamic) and behavioural levels of description. The model consists of a simulated robot controlled by a network of Kuramoto oscillators with homeostatic plasticity and the ability to develop behavioural preferences mediated by sensorimotor patterns. With only three oscillators, this simple model displays self-organized criticality in the form of robust 1/f noise and a wide multifractal spectrum. We show that the emergence of self-organized criticality and 1/f noise in our model is the result of three simultaneous conditions: a) non-linear interaction dynamics capable of generating stable collective patterns, b) internal plastic mechanisms modulating the sensorimotor flows, and c) strong sensorimotor coupling with the environment that induces transient metastable neurodynamic regimes. We carry out a number of experiments to show that both synaptic plasticity and strong sensorimotor coupling play a necessary role, as constituents of self-organized criticality, in the generation of 1/f noise. The experiments also shown to be useful to test the robustness of 1/f scaling comparing the results of different techniques. We finally discuss the role of conceptual models as mediators between nomothetic and mechanistic models and how they can inform future experimental research where self-organized critically includes sensorimotor coupling among the essential interaction-dominant process giving rise to 1/f noise.

Economía de la salud, modalidades de evaluación económica

La salud es un aspecto muy importante en la vida de cualquier persona, de forma que, al ocurrir cualquier contingencia que merma el estado de salud de un individuo o grupo de personas, se debe valorar estrictamente y en detalle las distintas alternativas destinadas a combatir la enfermedad. Esto se debe a que, la calidad de vida de los pacientes variará dependiendo de la alternativa elegida. La calidad de vida relacionada con la salud (CVRS) se entiende como el valor asignado a la duración de la vida, modificado por la oportunidad social, la percepción, el estado funcional y la disminución provocadas por una enfermedad, accidente, tratamiento o política (Sacristán et al, 1995). Para determinar el valor numérico asignado a la CVRS, ante una intervención, debemos beber de la teoría económica aplicada a las evaluaciones sanitarias para nuevas intervenciones. Entre los métodos de evaluación económica sanitaria, el método coste-utilidad emplea como utilidad, los años de vida ajustado por calidad (AVAC), que consiste, por un lado, tener en cuenta la calidad de vida ante una intervención médica, y por otro lado, los años estimados a vivir tras la intervención. Para determinar la calidad de vida, se emplea técnicas como el Juego Estándar, la Equivalencia Temporal y la Escala de Categoría. Estas técnicas nos proporcionan un valor numérico entre 0 y 1, siendo 0 el peor estado y 1 el estado perfecto de salud. Al entrevistar a un paciente a cerca de la utilidad en términos de salud, puede haber riesgo o incertidumbre en la pregunta planteada. En tal caso, se aplica el Juego Estándar con el fin de determinar el valor numérico de la utilidad o calidad de vida del paciente ante un tratamiento dado. Para obtener este valor, al paciente se le plantean dos escenarios: en primer lugar, un estado de salud con probabilidad de morir y de sobrevivir, y en segundo lugar, un estado de certeza. La utilidad se determina modificando la probabilidad de morir hasta llegar a la probabilidad que muestra la indiferencia del individuo entre el estado de riesgo y el estado de certeza. De forma similar, tenemos la equivalencia temporal, cuya aplicación resulta más fácil que el juego estándar ya que valora en un eje de ordenadas y abscisas, el valor de la salud y el tiempo a cumplir en esa situación ante un tratamiento sanitario, de forma que, se llega al valor correspondiente a la calidad de vida variando el tiempo hasta que el individuo se muestre indiferente entre las dos alternativas. En último lugar, si lo que se espera del paciente es una lista de estados de salud preferidos ante un tratamiento, empleamos la Escala de Categoría, que consiste en una línea horizontal de 10 centímetros con puntuaciones desde 0 a 100. La persona entrevistada coloca la lista de estados de salud según el orden de preferencia en la escala que después es normalizado a un intervalo entre 0 y 1. Los años de vida ajustado por calidad se obtienen multiplicando el valor de la calidad de vida por los años de vida estimados que vivirá el paciente. Sin embargo, ninguno de estas metodologías mencionadas consideran el factor edad, siendo necesario la inclusión de esta variable. Además, los pacientes pueden responder de manera subjetiva, situación en la que se requiere la opinión de un experto que determine el nivel de discapacidad del aquejado. De esta forma, se introduce el concepto de años de vida ajustado por discapacidad (AVAD) tal que el parámetro de utilidad de los AVAC será el complementario del parámetro de discapacidad de los AVAD Q^i=1-D^i. A pesar de que este último incorpora parámetros de ponderación de edad que no se contemplan en los AVAC. Además, bajo la suposición Q=1-D, podemos determinar la calidad de vida del individuo antes del tratamiento. Una vez obtenido los AVAC ganados, procedemos a la valoración monetaria de éstos. Para ello, partimos de la suposición de que la intervención sanitaria permite al individuo volver a realizar las labores que venía realizando. De modo que valoramos los salarios probables con una temporalidad igual a los AVAC ganados, teniendo en cuenta la limitación que supone la aplicación de este enfoque. Finalmente, analizamos los beneficios derivados del tratamiento (masa salarial probable) si empleamos la tabla GRF-95 (población femenina) y GRM-95 (población masculina).

A comparative study of consumption rates and preference for some species of aquatic plants by Tilapia rendalli

The daily consumption rates and preference of juvenile Tilapia rendalli for some macrophytes, Ceratophyllum demersum, Lagarosiphon major, Najas pectinatas and Valisneria aethiopica were determined. Fish were offered single macrophyte diets to determine daily consumption and a mixture of the 4 macrophytes in equal quantities to determine selection. Consumption rates were 821.50 mg, 829.05 mg, 940.00 mg and 2293.53 mg per fish per day, respectively. The differences in consumption rates were significant. Preference was shown for V.aethiopica, whilst C.demersum was least selected. Fish fed on single species lost weight whereas those fed on a variety of macrophytes gained in weight.

Prey preference of lingcod (Ophiodon elongatus), a top marine predator: implications for ecosystem-based fisheries management

Many highly exploited ecosystems are managed on the basis of single-species demographic information. This management approach can exacerbate tensions among stakeholders with competing interests who in turn rely on data with notoriously high variance. In this case study, an application of diet and dive survey data was used to describe the prey preference of lingcod (Ophiodon elongatus) in a predictive framework on nearshore reefs off Oregon. The lingcod is a large, fast-growing generalist predator of invertebrates and fishes. In response to concerns that lingcod may significantly reduce diminished populations of rockfishes (Sebastes spp.), the diets of 375 lingcod on nearshore reefs along the Oregon Coast were compared with estimates of relative prey availability from dive surveys. In contrast to the transient pelagic fishes that comprised 46% of lingcod diet by number, rockfishes comprised at most 4.7% of prey items. Rockfishes were the most abundant potential prey observed in dive surveys, yet they were the least preferred. Ecosystem-based fisheries management (EBFM) requires information about primary trophic relationships, as well as relative abundance and distribution data for multiple species. This study shows that, at a minimum, predation relative to prey availability must be considered before predator effects can be understood in a management context.