Cholinesterase inhibitors in advanced dementia with Lewy bodies: increase or stop?

INTRODUCTION There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. METHOD We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15 mg) to resolve rehyphen;emergent neuropsychiatric symptoms. RESULTS The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. CONCLUSION Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms.

Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C).

As pituitary function depends on the integrity of the hypothalamic-pituitary axis, any defect in the development and organogenesis of this gland may account for a form of combined pituitary hormone deficiency (CPHD). A mutation in a novel, tissue-specific, paired-like homeodomain transcription factor, termed Prophet of Pit-1 (PROP1), has been identified as causing the Ames dwarf (df) mouse phenotype, and thereafter, different PROP1 gene alterations have been found in humans with CPHD. We report on the follow-up of two consanguineous families (n = 12), with five subjects affected with CPHD (three males and two females) caused by the same nucleotide C to T transition, resulting in the substitution of Arg-->Cys in PROP1 at codon 120. Importantly, there is a variability of phenotype, even among patients with the same mutation. The age at diagnosis was dependent on the severity of symptoms, ranging from 9 months to 8 yr. Although in one patient TSH deficiency was the first symptom of the disorder, all patients became symptomatic by exhibiting severe growth retardation and failure to thrive, which was mainly caused by GH deficiency (n = 4). The secretion of the pituitary-derived hormones (GH, PRL, TSH, LH, and FSH) declined gradually with age, following a different pattern in each individual; therefore, the deficiencies developed over a variable period of time. All of the subjects entered puberty spontaneously, and the two females also experienced menarche and periods before a replacement therapy was necessary.

‘Stop spamming me!’: exploring information overload on Facebook

The problem of information overload on Facebook is exacerbating as users expand their networks. Growing quantity and increasingly poor quality of information on the Newsfeed may interfere with the hedonic experience of users resulting in frustration and dissatisfaction. In the long run, such developments threaten to undermine sustainability of the platform. To address these issues, our study adopts a grounded theory approach to explore the phenomenon of information overload on Facebook. We investigate main sources of information overload, identify strategies users adopt to deal with it as well as possible consequences. In-depth analysis of the phenomenon allows us to uncover individual peculiarities for identification of relevant information. Based on them we provide valuable recommendations for network providers.

Scp160p is required for translational efficiency of codon-optimized mRNAs in yeast

The budding yeast multi-K homology domain RNA-binding protein Scp160p binds to > 1000 messenger RNAs (mRNAs) and polyribosomes, and its mammalian homolog vigilin binds transfer RNAs (tRNAs) and translation elongation factor EF1alpha. Despite its implication in translation, studies on Scp160p's molecular function are lacking to date. We applied translational profiling approaches and demonstrate that the association of a specific subset of mRNAs with ribosomes or heavy polysomes depends on Scp160p. Interaction of Scp160p with these mRNAs requires the conserved K homology domains 13 and 14. Transfer RNA pairing index analysis of Scp160p target mRNAs indicates a high degree of consecutive use of iso-decoding codons. As shown for one target mRNA encoding the glycoprotein Pry3p, Scp160p depletion results in translational downregulation but increased association with polysomes, suggesting that it is required for efficient translation elongation. Depletion of Scp160p also decreased the relative abundance of ribosome-associated tRNAs whose codons show low potential for autocorrelation on mRNAs. Conversely, tRNAs with highly autocorrelated codons in mRNAs are less impaired. Our data indicate that Scp160p might increase the efficiency of tRNA recharge, or prevent diffusion of discharged tRNAs, both of which were also proposed to be the likely basis for the translational fitness effect of tRNA pairing.

Investigation of premature termination codon recognition in nonsense-mediated mRNA decay

Nonsense-mediated mRNA decay (NMD) is best known for its role in quality control of mRNAs, where it recognizes premature translation termination codons (PTCs) and rapidly degrades the corresponding mRNA. The basic mechanism of NMD appears to be conserved among eukaryotes: aberrant translation termination triggers NMD. According to the current working model, correct termination requires the interaction of the ribosome with the poly(A)-binding protein (PABPC1) mediated through the eukaryotic release factors 1 (eRF1) and 3 (eRF3). The model predicts that in the absence of this interaction, the NMD core factor UPF1 binds to eRF3 instead and initiates the events ultimately leading to mRNA degradation. However, the exact mechanism of how the decision between proper and aberrant (i.e. NMD-inducing) translation termination occurs is not yet well understood. We address this question using a tethering approach in which proteins of interest are bound to a reporter transcript into the vicinity of a PTC. Subsequently, the ability of the tethered proteins to inhibit NMD and thus stabilize the reporter transcript is assessed. Our results revealed that the C-terminal domain interacting with eRF3 seems not to be necessary for tethered PABPC1 to suppress NMD. In contrast, the N-terminal part of PABPC1, consisting of 4 RNA recognition motifs (RRMs) and interacting with eukaryotic initiation factor 4G (eIF4G), retains the ability to inhibit NMD. We find that eIF4G is able to inhibit NMD in a similar manner as PABPC1 when tethered to the reporter mRNA. This stabilization by eIF4G depends on two key interactions. One of these interactions is to PABPC1, the other is to eukaryotic initiation factor 3 (eIF3). These results confirm the importance of PABPC1 in inhibiting NMD but additionally reveal a role of translation initiation factors in the distinction between bona fide termination codons and PTCs.

Neoextractivismo, neodesarrollismo y proceso de acumulación de capital : ¿Superando el ciclo stop-and-go? Argentina, 2003-2012

Argentina ha entrado en una etapa de acumulación capitalista estabilizada bajo un nuevo proyecto de desarrollo hegemónico. Este proyecto avanza en la conformación de un patrón de acumulación de capital que busca superar las contradicciones entre el eje extractivista-rentista y el eje industrialista de las fracciones dominantes del capital. En esta ponencia discutiremos sí y de qué manera el histórico par campo-industria analizado en los clásicos modelos de acumulación à la Diamand, habrían perdido relevancia. Buscaremos analizar cómo las contradicciones latentes pretenden ser desplazas y qué lugar tiene la contradicción entre el capital y el trabajo en la nueva etapa que se está abriendo. El trabajo se basará en una reflexión histórico-conceptual apoyada en estadísticas construidas a partir de la información provista por los organismos públicos de estadísticas

Neoextractivismo, neodesarrollismo y proceso de acumulación de capital : ¿Superando el ciclo stop-and-go? Argentina, 2003-2012

Argentina ha entrado en una etapa de acumulación capitalista estabilizada bajo un nuevo proyecto de desarrollo hegemónico. Este proyecto avanza en la conformación de un patrón de acumulación de capital que busca superar las contradicciones entre el eje extractivista-rentista y el eje industrialista de las fracciones dominantes del capital. En esta ponencia discutiremos sí y de qué manera el histórico par campo-industria analizado en los clásicos modelos de acumulación à la Diamand, habrían perdido relevancia. Buscaremos analizar cómo las contradicciones latentes pretenden ser desplazas y qué lugar tiene la contradicción entre el capital y el trabajo en la nueva etapa que se está abriendo. El trabajo se basará en una reflexión histórico-conceptual apoyada en estadísticas construidas a partir de la información provista por los organismos públicos de estadísticas

Neoextractivismo, neodesarrollismo y proceso de acumulación de capital : ¿Superando el ciclo stop-and-go? Argentina, 2003-2012

Argentina ha entrado en una etapa de acumulación capitalista estabilizada bajo un nuevo proyecto de desarrollo hegemónico. Este proyecto avanza en la conformación de un patrón de acumulación de capital que busca superar las contradicciones entre el eje extractivista-rentista y el eje industrialista de las fracciones dominantes del capital. En esta ponencia discutiremos sí y de qué manera el histórico par campo-industria analizado en los clásicos modelos de acumulación à la Diamand, habrían perdido relevancia. Buscaremos analizar cómo las contradicciones latentes pretenden ser desplazas y qué lugar tiene la contradicción entre el capital y el trabajo en la nueva etapa que se está abriendo. El trabajo se basará en una reflexión histórico-conceptual apoyada en estadísticas construidas a partir de la información provista por los organismos públicos de estadísticas

Estudio de la influencia de los sistemas Stop/Start sobre el consumo de combustible y las emisiones de CO2 de un vehículo diesel en tráfico urbano.

Se presentan los resultados experimentales de un estudio realizado en el Laboratorio de Motores Térmicos de la ETSII de la UPM para evaluar el impacto en eficiencia energética y medioambiental de la tecnología Stop/Start en vehículos todoterreno con motor diesel, en condiciones de tráfico real urbano. Se realizaron ensayos urbanos con vehículos Land Rover Freelander2 en la zona central de la ciudad de Madrid midiendo la emisión instantánea de CO2 y de CO con equipos de medida de emisiones embarcados, y el consumo de combustible se calculó a partir del “balance de carbonos” midiendo el caudal de gases de escape mediante un caudalímetro de desarrollo propio. Se utilizaron dos vehículos todoterreno con motor diesel semejante, ambos cumpliendo los mismos límites Euro 4 para vehículos ligeros, uno convencional y otro adaptado con sistema Stop/Start. Se obtuvieron curvas de tendencia de consumo de combustible y de emisión de CO2 con la velocidad media, que demuestran el significativo efecto de mejora en la eficiencia energética de la versión de motor adaptado con sistema Stop/Start.

Comparing fuzzy and intelligent PI controllers in stop-and-go manoeuvres

The aim of this work was twofold: on the one hand, to describe a comparative study of two intelligent control techniques-fuzzy and intelligent proportional-integral (PI) control, and on the other, to try to provide an answer to an as yet unsolved topic in the automotive sector-stop-and-go control in urban environments at very low speeds. Commercial vehicles exhibit nonlinear behavior and therefore constitute an excellent platform on which to check the controllers. This paper describes the design, tuning, and evaluation of the controllers performing actions on the longitudinal control of a car-the throttle and brake pedals-to accomplish stop-and-go manoeuvres. They are tested in two steps. First, a simulation model is used to design and tune the controllers, and second, these controllers are implemented in the commercial vehicle-which has automatic driving capabilities-to check their behavior. A stop-and-go manoeuvre is implemented with the two control techniques using two cooperating vehicles.

La ciudad interior : infinitud y concavidad en la no-stop city (1970- 1971)

A finales de los 60 se había hecho evidente como la tecnificación del ambiente había permitido a algunas tipologías (supermercados, aparcamientos, fábricas) alcanzar profundidades construidas potencialmente ilimitadas e independizarse del afuera. La No-Stop City nace de una idea sencilla: extender esta tecnificación a la totalidad de lo construido para englobar, no sólo la práctica totalidad de funciones, sino, en última instancia, toda la ciudad. Esta operación tiene efectos paradójicos: a medida que la arquitectura crece, pierde la mayoría de características que la han definido tradicionalmente. Una disolución por hipertrofia que da lugar a un espacio homogéneo, cóncavo y potencialmente infinito. Pero, además de la pura factibilidad técnica, existen dos influencias clave y aparentemente contradictorias que explican esta apuesta por una ciudad interior e ilimitada: el marxismo y al Pop Art. El proyecto es, en muchos sentidos, un manifiesto construido que refleja la militancia de los miembros del grupo en el seno del marxismo italiano. Pero es también la plasmación del interés declarado del grupo por el Pop Art, la cultura popular y la sociedad de masas. La influencia cruzada de comunismo y consumismo explica esta “utopía cuantitativa” en la que se hacen coincidir la sociedad y la fábrica, la producción y el consumo. Una ciudad basada en la centralidad de los objetos de consumo y la subsiguiente pérdida de protagonismo de la arquitectura, en la que lo urbano, al tiempo que se extiende sin límites sobre el territorio, ignorando su exterioridad rural, disuelve el hogar como ámbito de privacidad, ignorando su interioridad doméstica. Un proyecto que, en la estela también de Marshall McLuhan, ilustra como pocos la conversión de lo urbano en una “condición” virtualmente omnipresente y que nos sigue interrogando con preguntas que son, por otra parte, eternas: ¿Qué es un edificio? ¿Qué es una ciudad?.

The Interior City Infinity and Concavity in the No-Stop City (1970-1971)

In the late 60s it had become clear how the environment technification had allowed some typologies (supermarkets, car parks, factories) to reach potentially unlimited built depths becoming, therefore, independent from the outside. The No-Stop City is born from a very simple idea: to extend this technification to the totality of built reality encompassing, not only almost all functions, but ultimately, the whole city. This operation has paradoxical effects: as architecture grows, it loses most of the features that have traditionally defined it. A dissolution by hypertrophy that gives rise to an homogeneous, concave and potentially infinite space. But beyond the pure technical feasibility, there are two key influences, seemingly contradictory, that explain this endeavor for an interior and endless city: Marxism and Pop Art. The project is, in many senses, a built manifesto reflecting the militancy of the group members within the Italian Marxism. But it is also the embodiment of the groups declared interest in Pop Art, popular culture and mass society. The cross-influence of communism and consumerism explains this "quantitative utopia" in which the society and the factory, the production and consumption, would match. A city based on the centrality of consumer products and the subsequent loss of prominence of architecture, in which the urban phenomenon, while spreading endlessly over territory, ignoring its rural exteriority, dissolves the home as a sphere of privacy, ignoring its domestic interiority. A project, also in the wake of Marshall McLuhan, that illustrates like few others the conversion of the urbane into a virtually omnipresent "condition" and that still interrogates us with questions that are, on the other hand, eternal: What is a building? What is a city?