Origins and efficiency of the electric industry regulation in Spain, 1910-1936

The aim of this paper is to discover the origins of utility regulation in Spain, and to analyse, from a microeconomic perspective, its characteristics and the impact of regulation on consumers and utilities. Madrid and the Madrilenian utilities are taken as a case study. The electric industry in the period studied was a natural monopoly2. Each of the three phases of production, generation, transmission and distribution, had natural monopoly characteristics. Therefore, the most efficient form to generate, transmit and distribute electricity was the monopoly because one firm can produce a quantity at a lower cost than the sum of costs incurred by two or more firms. A problem arises because when a firm is the single provider it can charge prices above the marginal cost, at monopoly prices. When a monopolist reduces the quantity produced, price increases, causing the consumer to demand less than the economic efficiency level, incurring a loss of consumer surplus. The loss of the consumer surplus is not completely gained by the monopolist, causing a loss of social surplus, a deadweight loss. The main objective of regulation is going to be to reduce to a minimum the deadweight loss. Regulation is also needed because when the monopolist fixes prices at marginal cost equal marginal revenue there would be an incentive for firms to enter the market creating inefficiency. The Madrilenian industry has been chosen because of the availability of statistical information on costs and production. The complex industry structure and the atomised demand add interest to the analysis. This study will also provide some light on the tariff regulation of the period which has been poorly studied and will complement the literature on the US electric utilities regulation where a different type of regulation was implemented.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.

The role of basalt replenishment in the generation of basaltic andesites of the ongoing activity at Arenal volcano, Costa Rica: evidence from clinopyroxene and spinel

The bulk composition of magma erupted from Volcan Arenal has remained nearly constant (SiO2 = 53.6-54.9 wt%; MgO = 5.0-4.5 wt%) during almost 30 years of continuous activity (1969-1996). None the less, clinopyroxene (cpx) phenocrysts and their spinel inclusions record a much more complex open-system evolution in which steady-state production of the erupted basaltic andesitic magma is linked to episodic injections of basalt into Arenal's magma conduit/reservoir system. High-resolution major element zoning profiles (electron microprobe) on a large number of phenocrysts (>14,000 analyses), tied to back-scattered electron (BSE) images, have been used to assess the compositional characteristics of the magmatic end members as well as the timing and dynamics of magma replenishment events. No two cpx phenocrysts have exactly the same zoning profile. The vast majority of our analyses record the crystallization of cpx (Cr2O3 < 0.12 wt%; Mg# = 65-79; Al/Ti = 2-7) from a liquid comparable to or more evolved than erupted magma compositions. However, half of all cpx grains are cored by high-Cr cpx (Cr2O3 = 0.2-0.72 wt%) or contain similar basaltic compositions as abrupt growth bands in phenocrysts with and without high-Cr cores; phenocrysts with high-Cr cpx occur throughout the ongoing activity. In a few cases, high-Cr cpx occurs very near the outer margin of the grain without an apparent growth hiatus, particularly in 1968/69 and 1992/93. The main conclusions are: (1) all basaltic andesitic lavas erupted at Arenal during the ongoing activity that began in July, 1968, are the products of magma mixing, (2) clinopyroxenes record multiple replenishment events of basaltic magma in contrast to the near constancy of erupted bulk compositions, (3) some phenocrysts preserve records of multiple interactions with basaltic magmas requiring magmatic processes to operate on time-scales shorter than residence times of some phenocrysts, (4) multiple occurrences of clinopyroxene with high-Cr rims suggest that basalt replenishment events have occurred with sub-decadal frequency and may predate eruption by months or less. From this we infer that Arenal volcano is underlain by a continuously active, small-volume magmatic reservoir maintained in quasi-steady state by basalt recharge over several decades. The monotony of erupting Arenal magmas implies that fractionation, recharge, ascent, and eruption are well balanced in order for magmas to be essentially uniform while containing phenocrysts with vastly different growth histories at the time of eruption.

Characterization of the effects of IL-17F on CHO cell line generation

CHO is the most commonly used mammalian host for the generation of cell lines allowing for the production of high quality therapeutic proteins. The generation of such cell lines is a lengthy and resource-intensive process requiring extensive screening in order to isolate candidates with optimal characteristics, such as growth, stability and productivity. For this reason, the biotechnology industry invests much effort in attempts to optimize CHO expression systems in order to streamline and shorten the cell line selection process. Based on preliminary observations of a facilitated selection of CHO-GS cell lines expressing members of the IL-17 cytokine family, this study investigates the use of IL-17F as a novel enhancing factor for CHO cell line generation. Using two different CHO expression systems (exploiting GS and DHFR-based selection), we demonstrated that IL-17F expression caused a significant increase in the occurrence of colonies during the selection process. All colonies selected produced substantial amounts of IL-17F, suggesting that benefits were conferred, during selection, to those cells expressing the cytokine. Furthermore, transgene expression levels were significantly increased when the selection pressure was raised to a level that would not normally be permissive for colony selection (i.e. 100 |o.M MSX for the CHO-GS expression system or 1000 nM MTX for the CHO-DHFR system). Finally, IL-17F expression was also found to enhance the rate of appearance of clones during single cell subcloning in the absence of selection pressure. Overall, these benefits have the potential to allow a substantial reduction in the length of cell line generation while significantly increasing cell line productivity. Nevertheless, we found that the high IL-17F expression levels required to convey enhancing effects was a limitation when attempting to co-express IL-17F and a recombinant soluble protein of therapeutic interest from independent CMV promoters within the same expression vector. In order to understand and overcome this limitation, studies were designed to characterize the IL-17F enhancing effect at the molecular and cellular level. Regular supplementation of recombinant biologically-active IL-17F into the culture medium during cell line selection was not able to reproduce the enhancing effects of endogenous IL-17F expression. In addition, increased IL-17F expression correlated with increased CHO-GS selection transgene expression at the single cell level. This data suggested a possible effect of IL-17F on viral promoter activity or transgene mRNA stability. It also provided direct evidence that the cells expressing the highest amounts of IL-17F obtained the most benefit. Overall data obtained from these study implied that IL-17F may act through an intracellular mechanism, possibly exerted during secretion. We therefore initiated experiments designed to determine the specific compartment(s) within which IL-17F triggers its effect. This work has identified IL-17F as a potentially powerful tool to optimize the CHO cell line generation process. The characterization of this enhancing effect at the molecular level has given us several insights into overcoming the current limitations, thus paving the way for the development of a viable technology that can be exploited within the biotechnology industry. - La CHO est la cellule hôte de mammifere la plus couramment utilisée dans la création de lignée cellulaire produisant des protéines thérapeutiques de haute qualité. La génération de ces lignées cellulaires est un processus long et exigeant l'utilisation de techniques de sélection robustes afin d'isoler des candidats possédants les caractéristiques optimales de croissance, de productivité et de stabilité d'expression. Les industries biopharmaceutiques ont investi beaucoup d'efforts afin d'optimiser les systèmes d'expression CHO dans le but raccourcir la longueur du procédé de sélection de lignées cellulaires et aussi d'en augmenter l'efficacité. A partir d'observations préliminaires obtenues lors de la génération de lignées cellulaires CHO- GS exprimant une cytokine appartenant à la famille des IL-17, nous avons réalisé une étude portant sur l'utilisation de l'IL-17F humaine (IL-17F) comme nouveau facteur d'optimisation pour la génération de lignées cellulaires CHO. Nous avons démontré, en utilisant les deux systèmes de sélection et d'expression CHO couramment utilisés (le premier exploitant la GS et l'autre basée sur la DHFR), que l'expression de l'IL-17F permet une augmentation significative de la fréquence d'apparition de colonies durant le processus de sélection de lignées cellulaires. Les différentes colonies sélectionnées expriment des quantités substantielles d'IL-17F, suggérant un effet bénéfique lors de la sélection qui serait exclusivement conféré aux cellules exprimant la cytokine. En outre, le niveau d'expression du transgene se trouve significativement augmenté lorsque la pression de sélection est portée à un niveau habituellement trop élevé pour permettre la sélection de colonies (soit 100 |JM MSX pour le système d'expression CHO-GS ou 1000 nM MTX pour le système CHO- DHFR). Enfin, l'expression d'IL-17F permet également d'améliorer la vitesse d'apparition de clones pendant une étape de sous-clonage en l'absence de pression de sélection. L'ensemble de ces effets bénéfiques permettent une réduction substantielle de la durée de génération de lignées cellulaires tout en augmentant considérablement la productivité des lignées obtenues. Néanmoins, nous avons constaté que la nécessité d'exprimer des niveaux élevés d'IL-17F afin obtenir l'ensemble de ses effets bénéfiques devient une contrainte lors de l'utilisation d'un vecteur d'expression composé de deux promoteurs CMV indépendants pour la co-expression de la cytokine et d'une protéine soluble présentant un intérêt thérapeutique. Afin de mieux comprendre et de surmonter cette limitation, plusieurs études ont été effectuées dans le but de mieux caractériser l'effet de IL-17F au niveau subcellulaire. L'apport régulier en IL-17F recombinante et biologiquement active dans le milieu de culture lors de la sélection de lignées cellulaires ne permet pas de reproduire les effets bénéfiques observés par l'expression endogène d'IL-17F. En outre, nous avons constaté que, lors de l'utilisation du système CHO- GS, l'augmentation d'expression de 1TL-17F est corrélée à un accroissement de l'expression du marqueur de sélection au niveau cellulaire. Ces résultats suggèrent un possible effet d'IL- 17F sur l'activité des promoteurs viraux et ainsi fournissent une preuve directe que les cellules exprimant de haut niveau d'IL-17F sont celles qui en profitent le plus. L'ensemble de ces observations mettrait en avant que l'effet d'IL-17F se ferait selon un mécanisme intracellulaire. Nous avons donc étudié le(s) compartiment(s) spécifique(s) dans lequel IL-17F pourrait exercer son effet. Ce travail a permis de définir IL-17F comme un puissant outil pour l'optimisation des procédés de génération de lignées cellulaires CHO. La caractérisation de cette amélioration de l'effet au niveau moléculaire nous a donné plusieurs indications sur la manière de dépasser les limitations actuelles, ouvrant ainsi la voie au développement d'une technologie viable qui peut être exploitée pars l'industrie biotechnologique.

Hypervitaminémie B12: implications cliniques et prise en charge [Therapeutic and clinical implications of elevated levels of vitamin B12].

In general practice, vitamin B12 levels are measured when searching an origin for an anemic status (usually megaloblastic anemia), for various neurological disorders (usually polyneuropathy) or for neurocognitive disorders. Although the pathologies associated with vitamin B12 deficiency are well known, hypervitaminemic B12 status is often fortuitous and frequent finding. The aim of this article is to present the disease entities associated with hypervitaminemia B12, the clinical implications of this dysvitaminosis and a practical approach when this laboratory abnormality is found.

Recommandations pour la prise en charge des formes oligoarticulaire et polyarticulaires (en dehors de la polyarthrite rhumatoïde) d'arthrite juvénile idiopathique [Guidelines for diagnosis and treatment of oligoarticular and polyarticular juvenile idiopathic arthritis].

A guideline group of pediatric rheumatologist experts elaborated guidelines related to the management of idiopathic juvenile arthritis in association with the Haute Autorité de santé (HAS). A systematic search of the literature published between 1998 and August 2008 and indexed in Pubmed was undertaken. Here, we present the guidelines for diagnosis and treatment in oligoarticular and polyarticular juvenile idiopathic arthritis (except for spondylarthropathy and rheumatoid arthritis).

Insuffisance veineuse chronique stade III: Prise en charge physio- thérapeutique [3rd degree chronic venous insufficiency: physiotherapy treatment]

A venous ulcer is the end result of a long pathological process where venous hypertension represents the principal cause of a number of complications. The physiotherapist by adapting various different therapeutic approaches improves the vascular, joint and respiratory problems of these patients.

. Phenotype/genotype correlation associated with a novel nonsense Glu20stop mutation in the Rp2 gene in a three-generation family with x-linked retinitis pigmentosa

Purpose: To assess the phenotype of patients in a large 3 generation Swiss family with X-linked retinitis pigmentosa (XLRP) due to a novel nonsense mutation Glu20stop in RP2 gene and to correlate with the genotype. Methods: 6 affected patients (1 male, 5 females, age range: 23 - 73 years) were assessed with a complete ophthalmologic examination. All had fundus autofluorescence images, standardised electroretinography, Goldmann visual fields and Optical Coherence Tomography. In addition, medical records of 2 affected male patients were reviewed. Blood sample was taken for molecular analysis. Results: The male patients were severely affected at a young age with early macular involvement. The youngest 23 y old male had also high myopia and vision of less than 0.05 according to Snellen EDTRS chart bilaterally. All 5 female carriers had some degree of rod-cone dystrophy, but no macular involvement. The visual acuity was 1.0 in the younger carriers, while the 73 years old had VA of 0.5. Two females had mild myopia (range -0.75 to -2) and one had anisometropia of 3.5D, with the more severely affected eye being myopic. Three out of 5 female carriers had optic nerve drusen. Conclusions: We report a novel Glu20stop mutation in RP2 gene, which is a rare cause of XLRP. Our description of severe phenotype in male patients with high myopia and early macular atrophy confirms previous reports. Unlike previous reports, all our female carriers had RP, but not macular involvement or high myopia. The identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.

Prise en charge de l'hémorragie du post-partum [Management of postpartum haemorrhage].

Today, postpartum hemorrhage remains a leading cause of maternal morbidity and mortality. Medical treatment, various surgical procedures and/or uterine artery embolisation have considerably reduced the risk of hysterectomy. It is important to identify the different risk factors of hemorrhage after delivery and to take the precautions to avoid it. A clear strategy defined by the obstetrical team is essential to decrease the delay in the management of this complication in order to increase the chances of a successful treatment.

Approche diagnostique et prise en charge des hémoptysies massives [Management of massive hemoptysis : a multidisciplinary approach]

Plus de cent maladies peuvent se manifester par une hémoptysie, qui peut être le reflet d'une pathologie sous-jacente potentiellement sérieuse. Elle n'est massive que dans 5% des cas et devient alors une entité clinique souvent dramatique, mortelle dans 30% des cas, qui nécessite une approche multidisciplinaire en milieu de soins intensifs. Quelques cas cliniques introduisent la discussion des aspects diagnostiques et thérapeutiques de leur prise en charge. Après avoir assuré la survie immédiate, l'origine du saignement sera localisée par une endoscopie qui permettra de réaliser un éventuel tamponnement endobronchique. Une artériographie doit ensuite être effectuée, afin de tenter d'obtenir l'hémostase par embolisation du réseau artériel bronchique responsable de l'épisode d'hémoptysie dans la majorité des cas.

'Next generation' biogeography: towards understanding the drivers of species diversification and persistence

The drivers of species diversification and persistence are of great interest to current biogeography, especially in those global biodiversity hotspots' harbouring most of Earth's animal and plant life. Classical multispecies biogeographical work has yielded fascinating insights into broad-scale patterns of diversification, and DNA-based intraspecific phylogeographical studies have started to complement this picture at much finer temporal and spatial scales. The advent of novel next-generation sequencing (NGS) technologies provides the opportunity to greatly scale up the numbers of individuals, populations and species sampled, potentially merging intraspecific and interspecific approaches to biogeographical inference. Here, we outline these prospects and issues by using the example of an undisputed hotspot, the Cape of southern Africa. We outline the current state of knowledge on the biogeography of species diversification within the Cape, review the literature for phylogeographical evidence of its likely drivers and mechanisms, and suggest possible ways forward based on NGS approaches. We demonstrate the potential of these methods and current bioinformatic issues with the help of restriction-site-associated DNA (RAD) sequencing data for three highly divergent species of the Restionaceae, an important plant radiation in the Cape. A thorough understanding of the mechanisms that facilitate species diversification and persistence in spatially structured, species-rich environments will require the adoption of novel genomic and bioinformatic tools in biogeographical studies.