Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons.

Evolutionary survival of a species is largely a function of its reproductive fitness. In mammals, a sparsely populated and widely dispersed network of hypothalamic neurons, the gonadotropin-releasing hormone (GnRH) neurons, serve as the pilot light of reproduction via coordinated secretion of GnRH. Since it first description, human GnRH deficiency has been recognized both clinically and genetically as a heterogeneous disease. A spectrum of different reproductive phenotypes comprised of congenital GnRH deficiency with anosmia (Kallmann syndrome), congenital GnRH deficiency with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism), and adult-onset hypogonadotropic hypogonadism has been described. In the last two decades, several genes and pathways which govern GnRH ontogeny have been discovered by studying humans with GnRH deficiency. More importantly, detailed study of these patients has highlighted the emerging theme of oligogenicity and genotypic synergism, and also expanded the phenotypic diversity with the documentation of reversal of GnRH deficiency later in adulthood in some patients. The underlying genetic defect has also helped understand the associated nonreproductive phenotypes seen in some of these patients. These insights now provide practicing clinicians with targeted genetic diagnostic strategies and also impact on clinical management.

Developments in the scientific and clinical understanding of gout.

Gout is the most common form of inflammatory arthritis in the elderly. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into the transporters that handle uric acid in the kidney as well as possible links between these transporters, hyperuricemia, and hypertension. The treatment of established hyperuricemia has also seen new developments. Febuxostat and PEG-uricase are two novel treatments that have been evaluated and shown to be highly effective in the management of hyperuricemia, thus enlarging the therapeutic options available to lower uric acid levels. Monosodium urate (MSU) crystals are potent inducers of inflammation. Within the joint, they trigger a local inflammatory reaction, neutrophil recruitment, and the production of pro-inflammatory cytokines as well as other inflammatory mediators. Experimentally, the uptake of MSU crystals by monocytes involves interactions with components of the innate immune system, namely Toll-like receptor (TLR)-2, TLR-4, and CD14. Intracellularly, MSU crystals activate multiple processes that lead to the formation of the NALP-3 (NACHT, LRR, and pyrin domain-containing-3) inflammasome complex that in turn processes pro-interleukin (IL)-1 to yield mature IL-1 beta, which is then secreted. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances in the understanding of hyperuricemia and gout provide new therapeutic targets for the future.

Infrastructures and productivity: an updated survey

The relationship between infrastructures and productivity has been the subject of an ongoing debate during the last two decades. The available empirical evidence is inconclusive and its interpretation is complicated by econometric problems that have not been fully solved. This paper surveys the relevant literature, focusing on studies that estimate aggregate production functions or growth regressions, and extracts some tentative conclusions. On the whole, my reading of the evidence is that there are sufficient indications that public infrastructure investment contributes significantly to productivity growth, at least for countries where a saturation point has not been reached. The returns to such investment are probably quite high in early stages, when infrastructures are scarce and basic networks have not been completed, but fall sharply thereafter. Hence, appropriate infrastructure provision is probably a key input for development policy, even if it does not hold the key to rapid productivity growth in advanced countries where transportation and communications needs are already adequately served.

Infected erythrocyte choline carrier inhibitors: exploring some potentialities inside Plasmodium phospholipid metabolism for eventual resistance acquisition

We have developed a model for designing antimalarial drugs based on interference with an essential metabolism developed by Plasmodium during its intraerythrocytic cycle, phospholipid (PL) metabolism. The most promising drug interference is choline transporter blockage, which provides Plasmodium with a supply of precursor for synthesis of phosphatidylcholine (PC), the major PL of infected erythrocytes. Choline entry is a limiting step in this metabolic pathway and occurs by a facilitated-diffusion system involving an asymmetric carrier operating according to a cyclic model. Choline transport in the erythrocytes is not sodium dependent nor stereospecific as demonstrated using stereoisomers of alpha and beta methylcholine. These last two characteristics along with distinct effects of nitrogen substitution on transport rate demonstrate that choline transport in the infected erythrocyte possesses characteristics quite distinct from that of the nervous system. This indicates a possible discrimination between the antimalarial activity (inhibition of choline transport in the infected erythrocyte) and a possible toxic effect through inhibition of choline entry in synaptosomes. Apart from the de novo pathway of choline, PC can be synthesized by N-methylation from phosphatidylethanolamine (PE). There is a de novo pathway for PE biosynthesis from ethanolamine in infected cells but phosphatidylserine (PS) decarboxylation also occurs. In addition, PE can be directly and abundantly synthesized from serine decarboxylation into ethanolamine, a pathway which is absent from the host. The variety of the pathways that exist for the biosynthesis of one given PL led us to investigate whether an equilibrium can occur between all PL metabolic pathways. Indeed, if alternative (compensative) pathway(s) can operate after blockage of the de novo PC biosynthesis pathway this would indicate a potential mechanism for resistance acquisition. Up until now, there is no evidence of such a compensative process occurring in Plasmodium-infected erythrocytes under physiological conditions. Besides, the discovery of a highly parasite-specific pathway (serine decarboxylation and the presence of PS synthase) constitutes a very attractive and promising target, which could be attacked if resistances are built up against choline analogs. Indeed, potential inhibitions of the serine decarboxylase pathway could be very useful in acting instead of, or in surgery with, choline analogs.

Technology, business models and network structure in the airline industry

Network airlines have been increasingly focusing their operations on hub airports through the exploitation of connecting traffic, allowing them to take advantage of economies of traffic density, which are unequivocal in the airline industry. Less attention has been devoted to airlines? decisions on point-to-point thin routes, which could be served using different aircraft technologies and different business models. This paper examines, both theoretically and empirically, the impact on airlines ?networks of the two major innovations in the airline industry in the last two decades: the regional jet technology and the low-cost business model. We show that, under certain circumstances, direct services on point-to-point thin routes can be viable and thus airlines may be interested in deviating passengers out of the hub.

Establiment d’un laboratori d’habilitats clíniques a la facultat de medicina de la Universitat de Barcelona

Per tal de millorar l'aprenentatge, actualment deficitari de les habilitats clíniques i dels procediments pràctics, la facultat va decidir implementar un laboratori d’habilitats. La Facultat de Medicina ha fet una important inversió per tal d’adequar un espai físic i adquirir diferents materials. En paral·lel es van identificar quines habilitats havien de ser ensenyats en el laboratori d’acord amb les dèficits observats prèviament. Es va dissenyar un curs optatiu sobre habilitats clíniques pels nostres estudiants de medicina i es van seleccionar i entrenar els diferents professors. El curs s’ha desenvolupat durant els tres últims anys. S'ha investigat el grau d’acceptació d’aquesta eina pels estudiants i professors utilitzant diferents tipus d’enquestes. Més de 300 estudiants de medicina per any han estat formats en el laboratori en diferents activitats, participant 20 professors i havent-se oferit diferents tallers sobre habilitats clíniques i procediments pràctics. Pels estudiants el laboratori es una excel·lent eina per incrementar la seva competència individual en habilitats clíniques i que es necessari estendre-la a tots els estudiants. Pels professors, el laboratori es una eina molt útil per millorar l’ensenyament clínic L'experiència ha estat molt positiva i molt útil en el procés de canvi curricular que es desenvolupa actualment a la nostra facultat. La nostra experiència pot servir de model per altres facultats de medicina de l’estat.

Dynamics of experimental populations of native and introduced blowflies (Diptera: Calliphoridae): mathematical modelling and the transition from asymptotic equilibrium to bounded oscillations

The equilibrium dynamics of native and introduced blowflies is modelled using a density-dependent model of population growth that takes into account important features of the life-history in these flies. A theoretical analysis indicates that the product of maximum fecundity and survival is the primary determinant of the dynamics. Cochliomyia macellaria, a blowfly native to the Americas and the introduced Chrysomya megacephala and Chrysomya putoria, differ in their dynamics in that the first species shows a damping oscillatory behavior leading to a one-point equilibrium, whereas in the last two species population numbers show a two-point limit cycle. Simulations showed that variation in fecundity has a marked effect on the dynamics and indicates the possibility of transitions from one-point equilibrium to bounded oscillations and aperiodic behavior. Variation in survival has much less influence on the dynamics.

Technology, business models and network structure in the airline industry

Network airlines have been increasingly focusing their operations on hub airports through the exploitation of connecting traffic, allowing them to take advantage of economies of traffic density, which are unequivocal in the airline industry. Less attention has been devoted to airlines' decisions on point-to-point thin routes, which could be served using different aircraft technologies and different business models. This paper examines, both theoretically and empirically, the impact on airlines' networks of the two major innovations in the airline industry in the last two decades: the regional jet technology and the low-cost business model. We show that, under certain circumstances, direct services on point-to-point thin routes can be viable and thus airlines may be interested in deviating passengers out of the hub. Keywords: regional jet technology; low-cost business model; point-to-point network; hub-and-spoke network JEL Classi…fication Numbers: L13; L2; L93

Spatio-temporal variations in reproductive patterns and population structure of Pasiphaea multidentata (Decapoda: Caridea) in the Blanes canyon and adjacent margin, North-western Mediterranean Sea

The bathyal faunal communities of the NW Mediterranean slopes have been studied consistently in the last two decades, with a special focus on population structure, trophic dynamics and benthopelagic coupling of commercial deep-sea decapod crustaceans and fishes (reviewed in Sardà et al. 2004) and associated species (Cartes and Sardà, 1993; Company and Sardà, 1997, 2000; Cartes et al., 2001; Company et al., 2001, 2003, 2004). One of the major topographic features in the North-western Mediterranean slope is the presence of submarine canyons. Canyons play a major role in funnelling energy and organic matter from the shelf to bathyal and abyssal depths (Puig et al., 2000), but the implications of this enhanced organic supply in the deep-sea benthic communities is still mostly unknown. Trophic supply can follow two major pathways – vertical deposition in the water column (Billett et al., 1983; Baldwin et al., 1998; Lampitt et al., 2001) or down-slope advection on the margins (Puig et al., 2001; Bethoux et al., 2002; Canals et al., 2006) – and can be a limiting factor in the deep-sea, being especially important in the oligotrophic Mediterranean Sea (Sardà et al., 2004). Differences in the quantity, quality and timing of organic matter input to the deep seafloor have been used to explain patterns of biomass and abundance in benthic communities (Levin et al., 1994; Gooday & Turley, 1990; Billett et al., 2001; Galéron et al., 2001; Puig et al., 2001; Gage, 2003) as well as other biological process and in particular the existence of seasonal reproduction (Tyler et al., 1994; Company et al., 2004 (MEPS). Reproduction is a highly energetic process tightly linked to food availability and quality.

The Rank Lecture: Has imaging told us anything new about human visual organisation?

The functional architecture of the occipital cortex is being studied with increasing detail. Functional and structural MR based imaging are altering views about the organisation of the human visual system. Recent advances have ranged from comparative studies with non-human primates to predictive scanning. The latter multivariate technique describes with sub-voxel resolution patterns of activity that are characteristic of specific visual experiences. One can deduce what a subject experienced visually from the pattern of cortical activity recorded. The challenge for the future is to understand visual functions in terms of cerebral computations at a mesoscopic level of description and to relate this information to electrophysiology. The principal medical application of this new knowledge has focused to a large extent on plasticity and the capacity for functional reorganisation. Crossmodality visual-sensory interactions and cross-correlations between visual and other cerebral areas in the resting state are areas of considerable current interest. The lecture will review findings over the last two decades and reflect on possible roles for imaging studies in the future.

Cutaneous plasmacytosis: an unusual presentation sharing features with POEMS syndrome?

Cutaneous plasmacytosis is a recently described skin disorder consisting of brown to red papules and nodules containing polyclonal plasmacytes. In this particular case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting with a primary hypothyroidisim. The last two signs have only been described to date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation, and might suggest an overlap between these two entities.

Identidades sonoras : OTO Creations

Este Proyecto Final describe y sintetiza un camino de más de 19 años de encantamiento con la música y sus infinitos senderos y posibilidades. En términos académicos, es un proyecto que expresa la polivalencia de la ESMUC, ya que conjuga disciplinas de distintas especialidades: composición, interpretación, grabación, producción, comercialización, promoción y gestión de la música. Es un Proyecto Final con cuatro apartados: una reflexión general acerca de la promoción y gestión musical en la actual "Sociedad de la Información", un proyecto de publicación, un plan de empresa, y finalmente una bobina de trabajos musicales publicitarios.

Invading freshwater snails and biological control in Martinique Island, French West Indies

Eight alien freshwater snail species were introduced into Martinique Island during the last 50 years. The introduced snails include four planorbids (Biomphalaria straminea, Helisoma duryi, Amerianna carinata and Gyraulus sp.), three thiarids (Melanoides tuberculata, M. amabilis and Tarebia granifera) and one ampullarid (Marisa cornuarietis). Four of these species rapidly colonized the whole Martinican hydrographic system whereas the other four remained restricted to some particular sites. The invasion processes were documented during the last 20 years and showed (i) a rapid invasion of the island by several morphs of M. tuberculata at the beginning of the 80's; (ii) the introduction of T. granifera in 1991 and M. amabilis in 1997; and (iii) the rapid spread of these last two species throughout the island. In the years following its introduction, M. tuberculata was used in biological control experiments against the snail hosts of schistosomiasis, B. glabrata and B. straminea. Experiments were conducted with success in several groups of water-cress beds which constituted the latest transmission sites for schistosomiasis at the beginning of the 80's. A malacological survey carried out in 2000 all over the island showed the absence of B. glabrata but the presence of some residual populations of B. straminea. Long-term studies carried out in Martinique have shown that the thiarids are able to maintain relatively stable populations over a long period of time, thus preventing recolonization by the snail hosts. Within this context the invasion of the hydrographic system of Martinique by thiarid snails has resulted in an efficient and sustainable control of the intermediate hosts of schistosomiasis.

Managing the size of the Olympic Games

The last two decades have seen dramatic increases in the size and scope of the Summer Olympic Games. In many ways, London 2012 reached even higher summits than the Beijing Games in 2008. This growth is a major challenge for the Olympics and its future organizers, as it is making the Games increasingly difficult to stage and has greatly reduced the number of cities capable of hosting them. This study shows how various participation and organization indicators have expanded over six Olympiads, from Barcelona 1992 to London 2012, and examines the reasons for this growth. It suggests ways of reducing the size of the Summer Olympic Games in order to make them more manageable and to encourage candidatures from smaller cities and countries.

Directive 2010/45/EU OF THE EU Parliament on standards of quality and safety of human organs intended for transplantation

Over the past 50 years organ transplantation has become an established worldwide practice, bringing immense benefits to hundreds of thousands of patients. The use of human organs (hereinafter â?~organsâ?T) for transplantation has steadily increased during the last two decades. Organ transplantation is now the most cost-effective treatment for end-stage renal failure, while for end-stage failure of organs such as the liver, lung and heart it is the only available treatment. Click here to download PDF 806kb You can read a summary of the document here