Characterization of the angiotensin II receptor antagonist TCV-116 in healthy volunteers.

The purpose of this study was to assess the inhibitory effect of TCV-116, an orally active angiotensin II (Ang II) antagonist, on the pressor action of exogenous Ang II and to determine the compensatory rise in plasma renin activity and Ang II levels. Twenty-three male volunteers were treated for 8 days in a double-blind fashion with either placebo or TCV-116 (1, 2, or 4 mg PO daily) and challenged on the first, fourth, and eighth days with repeated bolus injections of Ang II. An additional 4 subjects received 8 mg PO daily in a single-blind fashion. The inhibitory effect on the systolic blood pressure response to Ang II was long lasting and clearly dose related. Six hours after 4 mg TCV-116, the systolic blood pressure response to a given dose of Ang II was reduced to 40 +/- 4% and 35 +/- 8% of baseline value on days 1 and 8, respectively. TCV-116 induced a dose-related increase in plasma renin activity and Ang II levels that was more pronounced on the eighth than on the first day of drug administration. Despite this compensatory mechanism, the relation between the time-integrated systolic blood pressure response to Ang II and the time-integrated CV-11974 levels, the active metabolite of TCV-116, was not different between days 1 and 8. In conclusion, TCV-116 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of Ang II in men.

Marcas blancas : nuevo concepto comercial del sector alimentario

Productos sin una marca comercial publicitada ni reconocida, de envase y diseño aparentemente simples, vendidos generalmente en cadenas de supermercados, de precio reducido y con el logotipo de la empresa o cadena que los suministra, son los prototipos pertenecientes a las llamadas marcas blancas o de distribuidor, expresadas en la mayoría de los casos con las siglas MDD.Los primeros indicios de estos productos los situamos en Alemania justo despúes de su derrota en la Segunda Guerra Mundial. En un contexto de verdadera crisis los alemanes dejaron de prestar atención al valor de la marca propulsando así mercados dominados por precios bajos de productos sin marcas. La idea arreló con fuerza a las sociedades americanas y en 1869 en Gran Bretaña el supermercado Sainsbury lanzó al mercado su propia marca, ofreciendo una alta calidad juntamente con un excelente servicio a un precios claramente razonable. Estos productos también aparecieron en Francia en las manos de Coop. Más tarde, en la segunda parte de la década de los setenta, el fenómeno se translado a España con los productos Simago, donde empezó su denominación de marcas blancas, causa de sus sencillos envases, con frecuencia de color blanco, que indicaban sin más el producto contenido y el logotipo, en este caso de Simago. Pero si hay un hecho que marca el nacimiento de las marcas de distribuidor es cuando Carrefour lanzó en 1976 cinquenta productos libres o sin marcas del fabricante, con el fin de diferenciar el producto al incorporarle otra marca, la del distribuidor, ofreciendo precios competitivos sin disminuir la calidad. A partir de esta iniciativa las MDD adquierieron carta de naturaleza y como fénomeno consolidado fueron apareciendo en los distintos mercados de los paises más avanzados del mundo occidental.El intenso crecimiento de las marcas de distribuidor que se ha observado en estos últimos años en Europa, y consecuentemente también en España, a causa de la actual crisis económica, hizo despertar nuestro interés sobre estos nuevos y desconocidos conceptos de productos.¿Porqué la diferencia de precios es tan grande, cuando el producto es discretamente parecido?, ¿de dónde viene tanta polémica?, ¿qué hay detrás de la producción de las MDD?, ¿dónde nació éste concepto y cual puede ser su futuro?... Estas eran algunas de las preguntas cada vez que acudíamos a algún supermercado, veíamos algun anuncio o simplemente aparecían en los titulares de algún que otro periódico.Apasionadas de la actualidad y comprometidas por la economía, siempre nos ha gustado discutir nuestros puntos de vista distintos sobre estas cosas reales que nos distraen el día a día. Así, compartiendo nuestra incertidumbre, en un primer lugar nos decantamos por pensar que la calidad de estos porductos debería ser notablemente inferiror y que éste era el principal motivo de su precio reducido, pero hasta el momento todo se trataba de hipótesis no ontrastadas, y de pensamientos sin fundamento alguno.Nuestra duda continuaba y el hecho de pensar que eran de calidad inferior no obtuvo nuestra satisfacción. La sorpresa fue realmente grande cuando observamos que las pizzas Hacendado (productos del supermercado Mercadona) estaban producidas por la reconocida marca nacional de Casa Tarradellas, S.A. Aquí, nuestro interés para averiguar si realmente estos productos se distinguían, aumentó de manera considerable, hasta el punto que no consideramos desapropiado utilizar esta motivación para emprender un trabajo de búsqueda e investigación como éste. Además deseábamos un tema de actualidad e innovador, donde una investigación nos aportara más información que un libro de texto y que nos permitiese un trabajo diferente y a la vez motivador.Definitivamente ya lo teníamos: las marcas blancas o de distribuidor cumplían todos estos requisitos.Nuestra pasión por entender porqués nos llevó a concretar métodos de quizás demasiada envergadura. Una de las primeras alternativas que brilló fue centrarnos en una única comparativa llevada a cabo de manera exhaustiva entre dos productos de igual tipología, uno blanco y el otro nacional. Pero después de valorar listas de propuestas observarvamos que este método no nos daría unos resultados suficientemente fiables para poder cumplir con nuestros objetivos y sumándole la negativa de las empresas a dar la sufiente información para realizar el requerido análisis, decidimos en un primer lugar centrarnos en una parte puramente teórica, que consideramos que nos aportaría una buena base para empezar de manera estructural y no hacerlo desde cero.Esta primera parte del trabajo está encabezada por un estudio a nivel teórico del concepto general de marca y las estratégias de ésta que nos conduciran a profundizar en el concepto de marca blanca. à stas seran fuente de otro importante apartado teórico, las marcas de distribuidor, tema que lidera nuestro proyecto y que hemos considerado importante dar a conocer primero a nivel teórico el concepto de marca blanca así como los motivos de su nacimiento.Una vez realizada la parte teórica y lejos de anteriores proyectos infinitos, nuestros conocimientos sobre el tema estudiado se habían ampliado de manera considerable, las lecturas de diversas opiniones de consumidores en páginas de Internet o Blogs de aficionados a la economía, estudios muchos de ellos facilitados por la Agència Catalana de Consum (ACC), numerosos libros de marqueting y diferentes tesis y finalmente notícias de prensa nos dieron cuenta que a nivel teórico habíamos llegado a una comprensión completa de los conceptos que estábamos estudiando.Sabíamos quienes producian las marcas blancas, sabíamos quien las consumía con más frecuencia, teniamos listas infinitas de noticias de periódicos para hablar de actualidad, sabíamos los supermercados que habían decidico ofrecer estos productos, y quien producía todos estos productos. En fin, de saber, lo sabíamos. Pero nos encontramos que a pesar de saberlo casi todo sobre las ya familiares marcas blancas, no sabíamos como ordenar estas montañas de conocimientos que en pocas semanas habíamos adquirido.Fue este el momento crítico del trabajo, pero duró poco, no podía ser saber tanto y saber tan poco. Así que pensamos que la información que tanto habíamos leído y reeleído se podía clasificar en tres grandes grupos, o puntos de vista.El primero de ellos sería el punto de vista del fabricante, al fin y al cabo alguien debe producir, así que empezamos por donde se suele empezar, el principio.El segundo punto de vista sería el cliente de este fabricante, así que tendríamos a los distribuidores, que no son mas que grandes cadenas de supermercados o de grandes superfícies.Y finalmente, quien compraba a los grandes almacenes era ni más ni menos que el consumidor, así que el último punto de vista se trataba de estudiar el consumidor.Una vez comprendida y realizada la parte más práctica de las marcas de distribuidor, hemos incluido en el trabajo un apartado donde comentamos la actualidad y nos arriesgamos a hacer una pequeña hipótesis sobre cual puede ser el futuro de estas estratégias de marketing.Cabe mencionar que dada la gran envergadura actual de las MDD, preferimos centrarnos en la parte más primitiva de los productos blancos: los productos alimentarios de ámbito español. Esto permitió segmentar el complexo temario y no entrar en sectores téxtiles, de electrónica o en muchos otros ámbitos,donde hoy por hoy la marca blanca ha dejado también su huella, a la vez que concentrarnos en nuestro país, dado que las estratégias seguidas tienen distintos matices según cada país.Una vez estructurado y definido el trabajo, sólo nos faltaba ponernos manos a la obra y empezar a no parar, ahora sí todas nuestras dudas tendrían ya su respuesta.

Adaptive strategy for the statistical analysis of connectomes.

We study an adaptive statistical approach to analyze brain networks represented by brain connection matrices of interregional connectivity (connectomes). Our approach is at a middle level between a global analysis and single connections analysis by considering subnetworks of the global brain network. These subnetworks represent either the inter-connectivity between two brain anatomical regions or by the intra-connectivity within the same brain anatomical region. An appropriate summary statistic, that characterizes a meaningful feature of the subnetwork, is evaluated. Based on this summary statistic, a statistical test is performed to derive the corresponding p-value. The reformulation of the problem in this way reduces the number of statistical tests in an orderly fashion based on our understanding of the problem. Considering the global testing problem, the p-values are corrected to control the rate of false discoveries. Finally, the procedure is followed by a local investigation within the significant subnetworks. We contrast this strategy with the one based on the individual measures in terms of power. We show that this strategy has a great potential, in particular in cases where the subnetworks are well defined and the summary statistics are properly chosen. As an application example, we compare structural brain connection matrices of two groups of subjects with a 22q11.2 deletion syndrome, distinguished by their IQ scores.

Regulation of Spermatogenesis: Differentiation of GFP-labeled Stem Cells and the Function of Cytoplasmic Bridges

During spermatogenesis, different genes are expressed in a strictly coordinated fashion providing an excellent model to study cell differentiation. Recent identification of testis specific genes and the development of green fluorescence protein (GFP) transgene technology and an in vivo system for studying the differentiation of transplanted male germ cells in infertile testis has opened new possibilities for studying the male germ cell differentiation at molecular level. We have employed these techniques in combination with transillumination based stage recognition (Parvinen and Vanha-Perttula, 1972) and squash preparation techniques (Parvinen and Hecht, 1981) to study the regulation of male germ cell differentiation. By using transgenic mice expressing enhanced-(E)GFP as a marker we have studied the expression and hormonal regulation of beta-actin and acrosin proteins in the developmentally different living male germ cells. Beta-actin was demonstrated in all male germ cells, whereas acrosin was expressed only in late meiotic and in postmeiotic cells. Follicle stimulating hormone stimulated b-actin-EGFP expression at stages I-VI and enhanced the formation of microtubules in spermatids and this way reduced the size of the acrosomic system. When EGFP expressing spermatogonial stem cells were transplanted into infertile mouse testis differentiation and the synchronized development of male germ cells could be observed during six months observation time. Each colony developed independently and maintained typical stage-dependent cell associations. Furthermore, if more than two colonies were fused, each of them was adjusted to one stage and synchronized. By studying living spermatids we were able to demonstrate novel functions for Golgi complex and chromatoid body in material sharing between neighbor spermatids. Immunosytochemical analyses revealed a transport of haploid cell specific proteins in spermatids (TRA54 and Shippo1) and through the intercellular bridges (TRA54). Cytoskeleton inhibitor (nocodazole) demonstrated the importance of microtubules in material sharing between spermatids and in preserving the integrity of the chromatoid body. Golgi complex inhibitor, brefeldin A, revealed the great importance of Golgi complex i) in acrosomic system formation ii) TRA54 translation and in iii) granule trafficking between spermatids.

A Dethroned King? The Limits of State Infrastructural Power in France

Since the 1980s in Western Europe, centralized states' control over subnational territories has been deeply affected by processes of Europeanization and regionalization. These changes have raised the issue of state territorial restructuring in a particular fashion: what capacity have formerly centralized states retained to steer and control subnational territories? The article draws on Mann's concept of infrastructural power, which refers to the state's capacity to exercise control and implement political decisions over the national territory. The article applies the two main operationalizations of the concept, namely the capability of the state to exercise control and the weight of the state in the subnational territories. Empirically, the article focuses on the French state in two policy sectors (education and housing). Although France is a most likely case, this article challenges this expectation, and shows the limits of the French state's infrastructural power over the subnational territories since the late 1980s.

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In this paper, I reframe the long-standing controversy between 'psychological egoism', which argues that human beings never perform altruistic actions, and the opposing thesis of 'psychological altruism', which claims that human beings are, at least sometimes, capable of acting in an altruistic fashion. After a brief sketch of the controversy, I begin by presenting some representative arguments in favour of psychological altruism before showing that they can all be called into question by appealing to the idea of an unconscious self-directed motive. I will then point out that this argumentative strategy not only debunks the reasons for favouring psychological altruism, but also those for favouring psychological egoism; hence it is no use in settling the dispute between the two views. In the second part of the paper, I will try to break this deadlock by reframing the whole controversy, shifting it away from the concept of motive, towards the broader notion of motivation. As it turns out, this shift enables the debate to centre on altruistic emotions and their motivational power, thereby allowing evolutionary arguments to enter the debate and settle the dispute in favour of psychological altruism.

Blogit median työvälineenä

Opinnäytetyöni käsittelee blogeja median työvälineenä. Tarkoituksenani oli tutkia, miten media voi hyödyntää blogeja eli verkkopäiväkirjoja työssään. Pohdin myös, miten blogit ja internet haastavat ja muuttavat perinteistä mediaa. Työni on kirjallinen työ. Työni alussa esittelen blogit ja niiden historian lyhyesti. Blogien ja median suhdetta käsittelevä osa jakaantuu kolmeen osioon: media blogien käyttäjänä, media blogien tuottajana sekä blogien vaikutus mediaan. Aihepiiri on laaja, mutta blogikulttuuria ymmärtääkseen on tärkeää ymmärtää kokonaisuus. Työssäni huomasin, että blogeissa piilee valtavasti potentiaalia, myös median näkökulmasta, mutta Suomessa tuota potentiaalia ei tunnuta oikein ymmärtävän. Maailmalla, erityisesti USA:ssa blogeilla on jo pitkään ollut merkittävä asema ja vaikutusvaltaa yhteiskunnallisessa keskustelussa. Blogit ovat loputon tiedonlähde, ja niiden avulla löytää tietoa aiheesta kuin aiheesta. Ne myös mahdollistavat aivan uudenlaisen vuorovaikutuksen sekä yleisön että yhteistyötahojen kanssa. Median itsensä tuottamat blogit taas vapauttavat perinteisestä objektiivisuuden vaatimuksesta ja tarjoavat mahdollisuuden tuoda uusia näkökulmia uutisaiheisiin. Blogit myös haastavat perinteistä mediaa olemalla kaikille avoin julkaisukanava. Resurssiensa, kontaktiensa ja ammattitaitonsa ansiosta median ei tarvitse pelätä olemassaolonsa puolesta, mutta verkkomaailma kyllä vaikuttaa radikaalisti journalismin ja tiedonvälityksen periaatteisiin. Antoisinta on, jos media hyväksyy tilanteen ja ottaa haasteen vastaan.

The Lincoln Highway Association’s “Object Lesson:” The Seedling Mile in Linn County Iowa,

The Seedling Mile in Linn County, Iowa, was part of the Lincoln Highway Association’s so-called “object lesson” program that sought to graphically demonstrate, in the paving of selected one-mile demonstration sections, the benefits of concrete paving to improving road travel across the nation. Constructed in 1918-19, this Seedling Mile became much more than an object lesson and served as something of a battleground between two municipalities—Marion and Cedar Rapids—in their struggle over the county seat and their place on the Lincoln Highway. The Seedling Mile eventually became part of a continuously paved section of the Lincoln Highway between Chicago and Cedar Rapids, with the whole of the Lincoln Highway in Iowa paved in some fashion by the 1930s. In 2002, Linn County reconstructed Mt. Vernon Road from the City of Mt. Vernon to the west end of the Seedling Mile impacting the historic road section. An agreement between concerned government agencies resulted in this publication in partial mitigation of the impact to this historic road section under the guidelines of the National Historic Preservation Act.

Tumor-reactive, SSX-2-specific CD8+ T cells are selectively expanded during immune responses to antigen-expressing tumors in melanoma patients.

The SSX-2 gene encodes a tumor-specific antigen expressed in neoplasms of various histological types. By analyzing a tumor-infiltrated lymph node of a melanoma patient bearing an SSX-2-expressing tumor, we have recently identified the first SSX-2-derived CD8(+) T-cell epitope, that corresponds to peptide SSX-2(41-49), and is recognized by specific CTL in an HLA-A2 restricted fashion. Here, we have used fluorescent HLA-A2/SSX-2(41-49) peptide multimeric complexes to analyze the response to SSX-2(41-49) in melanoma patients and healthy donors. Multimer(+) CD8(+) T cells were readily detected in the majority of patients bearing SSX-2-expressing tumors and, at lower proportions, in patients with nonexpressing tumors and healthy donors. Importantly, isolated A2/SSX-2(41-49) multimer(+) CD8(+) T cells exhibited a large functional heterogeneity in terms of antigen recognition and tumor reactivity. SSX-2-specific CTLs isolated from tumor-infiltrated lymph node of antigen-expressing patients as well as from the corresponding peripheral blood mononuclear cells exhibited high functional avidity of antigen recognition and efficiently recognized antigen-expressing tumors. In contrast, SSX-2-specific CTLs isolated from patients with undetectable responses in the tumor-infiltrated lymph node, as well as from healthy donors, recognized the antigen with decreased functional avidity and were not tumor reactive. Together, these data indicate that CD8(+) T-cell responses to SSX-2(41-49) frequently occur in SSX-2-expressing melanoma patients and suggest that SSX-2(41-49)-specific CTLs of high avidity and tumor reactivity are selectively expanded during immune responses to SSX-2-expressing tumors in vivo.

Computerized advice on drug dosage to improve prescribing practice.

BACKGROUND: Maintaining therapeutic concentrations of drugs with a narrow therapeutic window is a complex task. Several computer systems have been designed to help doctors determine optimum drug dosage. Significant improvements in health care could be achieved if computer advice improved health outcomes and could be implemented in routine practice in a cost effective fashion. This is an updated version of an earlier Cochrane systematic review, by Walton et al, published in 2001. OBJECTIVES: To assess whether computerised advice on drug dosage has beneficial effects on the process or outcome of health care. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialized register (June 1996 to December 2006), MEDLINE (1966 to December 2006), EMBASE (1980 to December 2006), hand searched the journal Therapeutic Drug Monitoring (1979 to March 2007) and the Journal of the American Medical Informatics Association (1996 to March 2007) as well as reference lists from primary articles. SELECTION CRITERIA: Randomized controlled trials, controlled trials, controlled before and after studies and interrupted time series analyses of computerized advice on drug dosage were included. The participants were health professionals responsible for patient care. The outcomes were: any objectively measured change in the behaviour of the health care provider (such as changes in the dose of drug used); any change in the health of patients resulting from computerized advice (such as adverse reactions to drugs). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twenty-six comparisons (23 articles) were included (as compared to fifteen comparisons in the original review) including a wide range of drugs in inpatient and outpatient settings. Interventions usually targeted doctors although some studies attempted to influence prescriptions by pharmacists and nurses. Although all studies used reliable outcome measures, their quality was generally low. Computerized advice for drug dosage gave significant benefits by:1.increasing the initial dose (standardised mean difference 1.12, 95% CI 0.33 to 1.92)2.increasing serum concentrations (standradised mean difference 1.12, 95% CI 0.43 to 1.82)3.reducing the time to therapeutic stabilisation (standardised mean difference -0.55, 95%CI -1.03 to -0.08)4.reducing the risk of toxic drug level (rate ratio 0.45, 95% CI 0.30 to 0.70)5.reducing the length of hospital stay (standardised mean difference -0.35, 95% CI -0.52 to -0.17). AUTHORS' CONCLUSIONS: This review suggests that computerized advice for drug dosage has some benefits: it increased the initial dose of drug, increased serum drug concentrations and led to a more rapid therapeutic control. It also reduced the risk of toxic drug levels and the length of time spent in the hospital. However, it had no effect on adverse reactions. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimise the effect of computerised advice.

MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field.

The large spatial inhomogeneity in transmit B(1) field (B(1)(+)) observable in human MR images at high static magnetic fields (B(0)) severely impairs image quality. To overcome this effect in brain T(1)-weighted images, the MPRAGE sequence was modified to generate two different images at different inversion times, MP2RAGE. By combining the two images in a novel fashion, it was possible to create T(1)-weighted images where the result image was free of proton density contrast, T(2) contrast, reception bias field, and, to first order, transmit field inhomogeneity. MP2RAGE sequence parameters were optimized using Bloch equations to maximize contrast-to-noise ratio per unit of time between brain tissues and minimize the effect of B(1)(+) variations through space. Images of high anatomical quality and excellent brain tissue differentiation suitable for applications such as segmentation and voxel-based morphometry were obtained at 3 and 7 T. From such T(1)-weighted images, acquired within 12 min, high-resolution 3D T(1) maps were routinely calculated at 7 T with sub-millimeter voxel resolution (0.65-0.85 mm isotropic). T(1) maps were validated in phantom experiments. In humans, the T(1) values obtained at 7 T were 1.15+/-0.06 s for white matter (WM) and 1.92+/-0.16 s for grey matter (GM), in good agreement with literature values obtained at lower spatial resolution. At 3 T, where whole-brain acquisitions with 1 mm isotropic voxels were acquired in 8 min, the T(1) values obtained (0.81+/-0.03 s for WM and 1.35+/-0.05 for GM) were once again found to be in very good agreement with values in the literature.

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.

Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians

The human brainstem is a densely packed, complex but highly organised structure. It not only serves as a conduit for long projecting axons conveying motor and sensory information, but also is the location of multiple primary nuclei that control or modulate a vast array of functions, including homeostasis, consciousness, locomotion, and reflexive and emotive behaviours. Despite its importance, both in understanding normal brain function as well as neurodegenerative processes, it remains a sparsely studied structure in the neuroimaging literature. In part, this is due to the difficulties in imaging the internal architecture of the brainstem in vivo in a reliable and repeatable fashion. A modified multivariate mixture of Gaussians (mmMoG) was applied to the problem of multichannel tissue segmentation. By using quantitative magnetisation transfer and proton density maps acquired at 3 T with 0.8 mm isotropic resolution, tissue probability maps for four distinct tissue classes within the human brainstem were created. These were compared against an ex vivo fixated human brain, imaged at 0.5 mm, with excellent anatomical correspondence. These probability maps were used within SPM8 to create accurate individual subject segmentations, which were then used for further quantitative analysis. As an example, brainstem asymmetries were assessed across 34 right-handed individuals using voxel based morphometry (VBM) and tensor based morphometry (TBM), demonstrating highly significant differences within localised regions that corresponded to motor and vocalisation networks. This method may have important implications for future research into MRI biomarkers of pre-clinical neurodegenerative diseases such as Parkinson's disease.

When to carry eccentric products? Optimal retail assortment under consumer returns

To understand whether retailers should consider consumer returns when merchandising, we study howthe optimal assortment of a price-taking retailer is influenced by its return policy. The retailer selects itsassortment from an exogenous set of horizontally differentiated products. Consumers make purchase andkeep/return decisions in nested multinomial logit fashion. Our main finding is that the optimal assortmenthas a counterintuitive structure for relatively strict return policies: It is optimal to offer a mix of the mostpopular and most eccentric products when the refund amount is sufficiently low, which can be viewed asa form of risk sharing between the retailer and consumers. In contrast, if the refund is sufficiently high, orwhen returns are disallowed, optimal assortment is composed of only the most popular products (a commonfinding in the literature). We provide preliminary empirical evidence for one of the key drivers of our results:more eccentric products have higher probability of return conditional on purchase. In light of our analyticalfindings and managerial insights, we conclude that retailers should take their return policies into accountwhen merchandising.

On the role of retaliation in trade agreements

This paper analyzes the role of retaliation in trade agreements. It shows that, in the presenceof private information, retaliation can always be used to increase the welfare derived from suchagreements by the participating governments. In particular, it is shown that retaliation is anecessary feature of any efficient equilibrium.We argue that retaliation would not be necessary if governments could resort to internationaltransfers or export subsidies to compensate for terms-of-trade externalities. Within the currentworld trading system, though, in which transfers are seldom observed whereas export subsidiesare prohibited, the use of the remaining trade instruments in a retaliatory fashion might beoptimal. The model is used to interpret the retaliatory use of antidumping observed in the lastdecades, and the proliferation of these measures relative to other trade remedies.