Lymph node stromal cells negatively regulate antigen-specific CD4+ T cell responses

Lymph node (LN) stromal cells (LNSCs) form the functional structure of LNs and play an important role in lymphocyte survival and the maintenance of immune tolerance. Despite their broad spectrum of function, little is known about LNSC responses during microbial infection. In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell-mediated Ag presentation resulted in slower contraction of Ag-specific CD4(+) T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4(+) T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.

Urethral recurrence in women with orthotopic bladder substitutes: A multi-institutional study.

OBJECTIVES To evaluate risk factors for urethral recurrence (UR) in women with neobladder. MATERIAL AND METHODS From 1994 to 2011, 297 women (median age = 54y; interquartile range: 47-57) underwent radical cystectomy with ileal neobladder for bladder cancer in 4 centers. None of the patients had bladder neck involvement at preoperative assessment. Univariable and multivariable analyses were used to estimate recurrence-free survival and overall survival. The median follow-up was 64 months (interquartile range: 25-116). RESULTS Of the 297 patients, 81 developed recurrence (27%). The 10- and 15-year recurrence-free survival rates were 66% and 66%, respectively. The 10- and 15-year overall survival rates were 57% and 55%, respectively. UR occurred in 2 patients (0.6%) with solitary urethral, 4 (1.2%) with concomitant urethral and distant recurrence, and 1 with concomitant urethral and local recurrence (0.3%). Bladder tumors were located at the trigone in 27 patients (9.1%). None of these patients developed UR. Lymph node tumor involvement was present in 60 patients (20.2%). On univariable and multivariable analyses, pathologic tumor and nodal stage were independent predictors for the overall risk of recurrence. UR was associated with a positive final urethral margin status (P<0.001) whereas no significant associations were found for carcinoma in situ, pathologic tumor and nodal stage, and bladder trigone involvement. CONCLUSIONS In this series, only 0.6% of women developed solitary UR. A positive final urethral margin was associated with an increased risk of UR. Women with involvement of the bladder trigone were not at higher risk of UR.

Does somatostatin or gastric inhibitory peptide receptor expression correlate with tumor grade and stage in gut neuroendocrine tumors?

BACKGROUND/AIMS Important characteristics of neuroendocrine neoplasms (NEN) for prognosis and therapeutic decisions are the MIB-1 proliferative index (tumor grade) and tumor stage. Moreover, these tumors express peptide hormone receptors like somatostatin and gastric inhibitory peptide (GIP) receptors which represent important established and potential future targets, respectively, for molecular imaging and radiotherapy. However, the interrelation between tumor proliferation, stage, and peptide receptor amounts has never been assessed. METHODS In 114 gastrointestinal and bronchopulmonary NEN, the proliferative rate assessed with MIB-1 immunohistochemistry and tumor stage were compared with the somatostatin type 2 receptor (sst2) and GIP receptor expression measured quantitatively with in vitro receptor autoradiography. RESULTS NEN generally showed high sst2 and GIP receptor expression. GIP receptor but not sst2 expression correlated with the MIB-1 index. GIP receptor levels gradually increased in a subset of insulinomas and nonfunctioning pancreatic NEN, and decreased in ileal and bronchopulmonary NEN with increasing MIB-1 rate. MIB-1 levels were identified, above which GIP receptor levels were consistently high or low. These MIB-1 levels were clearly different from those defining tumor grade. In grade 3 NEN, GIP receptor levels were always low, while sst2 levels were variable and sometimes extremely high. Conversely, sst2 expression correlated more frequently with tumor stage than GIP receptor expression, with metastasized NEN showing higher sst2 levels than localized tumors. CONCLUSIONS sst2, a clinically crucial molecular target, shows variable and unpredictable expression in NEN irrespective of tumor grade. Therefore, each NEN should be tested for sst2 if clinical applications with somatostatin analogs are considered. Conversely, the potential future role of GIP receptors as molecular targets in NEN may be dependent on the MIB-1 level.

Open radical cystectomy: still the gold standard for muscle invasive bladder cancer

INTRODUCTION Muscle invasive bladder cancer is an unforgiving disease, and if untreated, it leads to death within 2 years of the diagnosis in >85 % of the patients. Long-term oncologic efficacy remains the ultimate standard that all procedures have to be measured by. In the past decades, open radical cystectomy (RC), extended pelvic lymph node dissection (PLND), and urinary diversion have been established as the gold standard. In the last few years, however, growing attention has been set on robotic-assisted radical cystectomy (RARC). RESULTS Even in the very long term, open RC has good oncological results and if an ileal neobladder is performed excellent functional results. Follow-up of patients after open RC exceeds more than a decade which is unsurpassed by any other technique. Its outcomes have been proven to be durable and cost-effective. Least perioperative complications as well as best oncological and functional results can be achieved if open RC and urinary diversion were performed in a high-volume hospital by high-volume surgeons and an experienced team. CONCLUSIONS Despite upcoming new technologies such as RARC, open RC following extended (PLND) remains the gold standard treatment for high-grade muscle invasive bladder cancer.

There is a place for radical cystectomy and urinary diversion, including orthotopic bladder substitution, in patients aged 75 and older: Results of a retrospective observational analysis from a high-volume center

INTRODUCTION The incidence of cancer increases with age and owing to the changing demographics we are increasingly confronted with treating bladder cancer in old patients. We report our results in patients>75 years of age who underwent open radical cystectomy (RC) and urinary diversion. MATERIAL AND METHODS From January 2000 to March 2013, a consecutive series of 224 old patients with complete follow-up who underwent RC and urinary diversion (ileal orthotopic bladder substitute [OBS], ileal conduit [IC], and ureterocutaneostomy [UCST]) were included in this retrospective single-center study. End points were the 90-day complication rates (Clavien-Dindo classification), 90-day mortality rates, overall and cancer-specific survival rates, and continence rates (OBS). RESULTS Median age was 79.2 years (range: 75.1-91.6); 35 of the 224 patients (17%) received an OBS, 178 of the 224 patients (78%) an IC, and 11 of the 224 patients (5%) an UCST. The 90-day complication rate was 54.3% in the OBS (major: Clavien grade 3-5: 22.9%, minor: Clavien Grade 1-2: 31.4%), 56.7% in the IC (major: 27%, minor: 29.8%), and 63.6% in the UCST group (major: 36.4%, minor: 27.3%); P = 0.001. The 90-day mortality was 0% in the OBS group, 13% in the IC group, and 10% in the UCST group (P = 0.077). The Glasgow prognostic score was an independent predictor of all survival parameters assessed, including 90-day mortality. Median follow-up was 22 months. Overall and cancer-specific survivals were 90 and 98, 47 and 91, and 11 and 12 months for OBS, IC, and UCST, respectively. In OBS patients, daytime continence was considered as dry in 66% and humid in 20% of patients. Nighttime continence was dry in 46% and humid 26% of patients. CONCLUSION With careful patient selection, oncological and functional outcome after RC can be good in old patients. Old age as the sole criterion should not preclude the indication for RC or the option of OBS. In old patients undergoing OBS, satisfactory continence results can be achieved.

Driving and emergency braking may be impaired after tibiotalar joint arthrodesis: conclusions after a case series.

PURPOSE To assess whether reaction time (RT) and movement time (MT), as the two components of the total brake response time (TBRT) and brake force (BF) are different in patients with a foot joint arthrodesis in comparison to controls. METHODS The study was a comparative case series in a driving simulator under realistic driving conditions. Mobile patients without a walker, ≥6 months after surgery who were driving a car and had no neurological co-morbidity, knee or hip joint prosthesis were included in the study. The selection criteria resulted in 12 patients with right tibiotalar joint arthrodesis (TTJA) and 12 patients with another right foot joint arthrodesis (OFJA), who were compared to 17 individuals without any ankle-joint pathology. For TBRT, an empirical safe driving threshold of 700 ms was used. The outcome measures were RT, MT, TBRT, BF and McGuire score. RESULTS MT (p = 0.034) and TBRT (p = 0.026) were longer in TTJA patients in comparison with the controls. Also, more patients with TTJA than patients with OFJA and controls exceeded the safe driving threshold (p = 0.028). The outcomes in OFJA patients and in controls were comparable. The McGuire score was similar between the TTJA and OFJA patients (p = 0.26). CONCLUSIONS Significantly slower MT and TBRT, and significantly more patients exceeding the safe driving threshold, were observed after a tibiotalar-joint arthrodesis in comparison to the controls. Patients with OFJAs were not significantly different from the controls. Driving and emergency braking may be impaired after tibiotalar-joint arthrodesis.

STUDIES OF DISULFOTON TOLERANCE IN RATS

Disulfoton (O,O, diethyl S-2-(ethylthio)ethyl phosphorodithioate) and other organophosphorus ester compounds are insecticides which inhibit acetylcholinesterase. Chemicals of this class cause signs of toxicity in mammals which are referable to acculmulation of acetylcholine at neuroeffector sites. A tolerance to this toxic action can be induced in experimental animals by giving multiple, sublethal doses of the compounds. There is strong evidence that disulfoton tolerance occurs because of a reduction in the sensitivity of tissues in the affected animals to acetylcholine.^ Experiments were designed to test the possibility that a decrease in the number of muscarinic cholinergic receptors could be downmodulating the sensitivity of tissues to acetylcholine. It was found that, concomitant with the onset of disulfoton tolerance, there was a decrease relative to control values in the specific binding of {('3)H} quinuclidinyl benzilate ({('3)H}QNB, a compound which selectively labels muscarinic cholinergic receptors) to homogenates of rat brain and ileal muscle. The decrease in {('3)H}QNB binding was due to a reduction in the density of muscarinic receptors. There was, however, no alteration in the binding of {('3)H} QNB, or the muscarinic agonists {('3)H} oxotremorine-M and oxotremorine to atria from disulfoton-tolerant rats. The possibility that cardiac tissue was not subsensitive to cholinergic agonists was ruled out in experiments testing the effect of the muscarinic agonist carbachol on heart rate in vivo, and the negative chronotropic effect of oxotremorine on atria from disulfoton-tolerant rats: a clear reduction in the sensitivity to cholinergic agonists was seen in each case. It was, therefore concluded that the specificity and temporal correlation of {('3)H}QNB binding decreases suggested that the loss of muscarinic receptors might play a role in modulating the sensitivity of several tissues to acetylcholine, but that other mechanisms also contribute to the tolerance phenomenon.^ Other experiments revealed that disulfoton tolerance, as measured by resistance to the lethal effects of carbachol, could be induced by feeding rats low levels of the organophosphorus ester in the diet. The concentration of disulfoton used inhibited acetylcholinesterase, but not to the extent that overt signs of toxicity were observed. These results suggested that tolerance to organophosphorus ester insecticides could be induced in rodents with a dosing scheme which more closely modeled the sort of low level exposures which would be expected in humans environmentally or occupationally in contact with these compounds. ^

Risk factors and inflammatory markers in pouchitis

Individuals who do not respond to medical therapy for ulcerative colitis (UC) often undergo proctocolectomy followed by ileal-pouch anal anastomosis (IPAA) in hopes of resolving symptoms associated with UC. Inflammation of the ileal pouch, better known as pouchitis, is the most common complication of the IPAA procedure. The causes and development of pouchitis is not well understood. To better understand pathogenesis of pouchitis, pouch aspirates of patients having undergone IPAA were quantitatively analyzed for fecal IL-8, IL-17, and IL-23 levels. According to published literature IL-8 has been linked to pouchitis whereas IL-17 and IL-23 are associated with intestinal inflammation. The study had 80 participants, 33 patients diagnosed with Crohn's Disease (CD) of the pouch, 19 patients diagnosed with pouchitis, and 28 diagnosed with having normal pouches. Patient characteristics and histopathological findings for all patients were noted and statistically compared in addition to fecal cytokine levels. This study supported previous literature that IL-8 production was associated with pouch inflammation. However, IL-17 and IL-23 levels in both CD of the pouch and pouchitis were not significantly different to the levels noted in normal pouch.^

Effects of increasing levels of pea hulls in the diet on productive performance, development of the gastrointestinal tract, and nutrient retention of broilers from one to eighteeen days of age

The effects of inclusion of pea hulls (PH) in the diet on growth performance, development of the gastrointestinal tract and nutrient retention were studied in broilers from 1 to 18d of age. There were a control diet based on low fibre ingredients (69.3 total dietary fibre (16.1g crude fibre/kg)) and three additional diets that resulted from the dilution of the basal diet with 25, 50 and 75g PH/kg (81.2, 93.2, and 105.1g total dietary fibre/kg diet, respectively). Each treatment was replicated six times and the experimental unit was a cage with 12 chicks. Growth performance, development of the gastrointestinal tract and the coefficients of total tract apparent retention (CTTAR) of nutrients were recorded at 6, 12 and 18d of age. In addition, jejunal morphology was measured at 12 and 18d and the coefficients of apparent ileal digestibility (CAID) of nutrients at 18d of age. Pea hulls inclusion affected all the parameters studied. The inclusion of 25 and 50g PH/kg diet improved growth performance as compared to the control diet. The relative weight (g/kg body weight) of proventriculus (P≤0.01), gizzard (P≤0.001) and ceca (P≤0.05) increased linearly as the level of PH in the diet increased. The inclusion of PH affected quadratically (P≤0.01) villus height:crypt depth ratio with the highest value shown at 25g PH/kg. In general, the CTTAR and CAID of nutrients increased linearly and quadratically (P≤0.05) with increasing levels of PH, showing maximum values with PH level between 25 and 50g/kg diet. We conclude that the size of the digestive organs increases with increasing levels of PH in the diet. In general, the best performance and nutrient digestibility values were observed with levels of PH within the range of 25 and 50g/kg. Therefore, young broilers have a requirement for a minimum amount of dietary fibre. When pea hulls are used as a source of fibre, the level of total dietary fibre required for optimal performance is within the range of 81.2–93.2g/kg diet (25.6–35.0g crude fibre/kg diet). An excess of total dietary fibre (above 93.2g/kg diet) might reduce nutrient digestibility and growth performance to values similar to those observed with the control diet.

Effect of sugar beet pulp fibre fractions on growth performance, fecal digestibility and digestive physiology in rabbits around weaning

The present study investigated the effect of the different fibre components of sugar beet pulp (SBP) on growth performance and some digestive traits. Four semi-synthetic diets were formulated with similar NDF (33% DM) and protein (16% DM) level. Control diet was formulated to contain the lowest level of soluble fibre (3% DM) and SBP diet the highest (9%). The soluble (pectins) and insoluble fractions of SBP were studied in other two diets (Pectin and InsSBP diets). A total of 136 weanling rabbits (25 d of age) was housed individually, randomly assigned to 4 experimental groups, and fed ad libitum with the experimental diets during 10 days after weaning. The type of diet did not affect growth rate and stomach pH. Animals fed with SBP diet showed higher DM and NDF digestibility (4 and 83%, respectively), gain:feed ratio (13%), cecal and total tract weight (13 and 9%) and ileal viscosity (148%) than rabbits fed the Control diet, but lower cecal pH (9%). Pectin diet increased ileal viscosity and decreased the weight of stomach content with respect to SBP diet. Rabbits fed InsSBP diet showed similar results to SBP diet but lower ileal viscosity and cecal pH than those fed Pectin diet. In conclusion, SBP and their soluble and insoluble fractions are well digested in young rabbits. However the soluble and insoluble fibre of SBP produce different effects in the gastrointestinal tract.

Utilización de bolsas ANKOM® en la determinación de la digestibilidad de la materia seca in vitro en conejos.

La metodología de digestibilidad in vitro de la materia seca (DMSiv) desarrollada por Ramos et al. (1992) para predecir la digestibilidad de la materia seca y valor nutricional de diferentes alimentos comúnmente utilizados en la alimentación de conejos, ha sido estandarizada y validada por diferentes laboratorios (Villamide et al. 2008 y Carabaño et al. 2008), demostrándose su fiabilidad, reproducibilidad y repetibilidad. Uno de los puntos críticos de las metodologías gravimétricas es la filtración con crisol, ya que las propiedades físicas junto con la composición química de diversas materias primas dificultan este proceso y aumentan la variabilidad en los resultados (Mertens, 2002). Por otra parte la digestión individual de las muestras limita la capacidad de análisis. Con la finalidad de corregir estas limitaciones se propuso como alternativa el uso de bolsas ANKOM ® , ya utilizadas en el análisis secuencial de Van Soest (Kenneth et al., 1999), digeridas colectivamente en un mismo recipiente. Además de la utilización de bolsas, como novedad se incluyó al final de la digestibilidad un lavado adicional de las bolsas. El objetivo de este trabajo fue determinar la validez de esta modificación en la digestibilidad in vitro ileal (dos pasos) y fecal (tres pasos)

Efectos de tres distintos aportes alimenticios restringidos como inductores de la muda en gallinas ponedoras, sobre la pérdida de peso vivo, la regresión de ovario y oviducto y los resultados productivos

La producción de huevos disminuye a medida que las ponedoras envejecen. Un método para contrarrestar, al menos parcialmente, esta evolución natural del rendimiento productivo es la muda inducida. El rendimiento productivo de las gallinas tras la muda se debe a un proceso de rejuvenecimiento fisiológico de las aves, relacionado con la regresión del ovario y del oviducto durante la muda, siendo la pérdida de peso corporal decisiva para la regresión de estos órganos (Brake y Thaxton , 1979). En este trabajo estudiamos los efectos de 3 dietas distintas, utilizadas para inducir la muda (salvado de trigo, cebada y pienso comercial suministrado de forma restringida), sobre la pérdida de peso vivo, sobre la regresión del ovario y del oviducto, y sobre los rendimientos productivos posteriores, en gallinas ponedoras de 2 estirpes comerciales, alojadas con dos densidades diferentes (4 y 6 gallinas, por jaula). Se trabajó con 120 gallinas de cada estirpe, sacrificándose 36 animales (18+18) para poder evaluar la regresión del ovario-oviducto. La menor pérdida de peso se produjo con el salvado y con la cebada, aunque la intensidad de puesta (IP), en las 6 primeras semanas postmuda no varió entre tratamientos, excepto en gallinas ligeras mudadas con salvado de trigo, que alcanzaron una IP significativamente menor . Tampoco tuvo efecto significativo el número de gallinas por jaula sobre la IP, ni sobre la pérdida de peso.

Diseño y aplicación de una metodología prospectiva para la determinación de los condicionantes futuros del crecimiento de los grandes buques portacontenedores

Durante las últimas décadas se observa una tendencia sostenida al crecimiento en las dimensiones de los grandes buques portacontenedores, que produce, que las infraestructuras portuarias y otras destinadas al tráfico de contenedores deban adaptarse para poder brindar los servicios correspondientes y mantenerse competitivas con otras para no perder el mercado. Esta situación implica importantes inversiones y modificaciones en los sistemas de transporte de contenedores por el gran volumen de carga que se debe mover en un corto periodo de tiempo, lo que genera la necesidad de tomar previsiones relacionadas con la probable evolución a futuro de las dimensiones que alcanzarán los grandes buques portacontenedores. En relación a los aspectos citados surge la inquietud de determinar los condicionantes futuros del crecimiento de los grandes buques portacontenedores, con una visión totalizadora de todos los factores que incidirán en los próximos años, ya sea como un freno o un impulso a la tendencia que se verifica en el pasado y en el presente. En consideración a que el tema a tratar y resolver se encuentra en el futuro, con un horizonte de predicción de veinte años, se diseña y se aplica una metodología prospectiva, que permite alcanzar conclusiones con mayor grado de objetividad sobre probables escenarios futuros. La metodología prospectiva diseñada, conjuga distintas herramientas metodológicas, cualitativas, semi-cuantitativas y cuantitativas que se validan entre sí. Sobre la base del pasado y el presente, las herramientas cuantitativas permiten encontrar relaciones entre variables y hacer proyecciones, sin embargo, estas metodologías pierden validez más allá de los tres a cuatro años, por los vertiginosos y dinámicos cambios que se producen actualmente, en las áreas política, social y económica. Las metodologías semi-cuantitativas y cualitativas, empleadas en forma conjunta e integradas, permiten el análisis de circunstancias del pasado y del presente, obteniendo resultados cuantitativos que se pueden proyectar hacia un futuro cercano, los que integrados en estudios cualitativos proporcionan resultados a largo plazo, facilitando considerar variables cualitativas como la creciente preocupación por la preservación del medio ambiente y la piratería. La presente tesis, tiene como objetivo principal “identificar los condicionantes futuros del crecimiento de los grandes buques portacontenedores y determinar sus escenarios”. Para lo cual, la misma se estructura en fases consecutivas y que se retroalimentan continuamente. Las tres primeras fases son un enfoque sobre el pasado y el presente, que establece el problema a resolver. Se estudian los antecedentes y el estado del conocimiento en relación a los factores y circunstancias que motivaron y facilitaron la tendencia al crecimiento de los grandes buques. También se estudia el estado del conocimiento de las metodologías para predecir el futuro y se diseña de una metodología prospectiva. La cuarta fase, denominada Resultados, se desarrolla en distintas etapas, fundamentadas en las fases anteriores, con el fin de resolver el problema dando respuestas a las preguntas que se formularon para alcanzar el objetivo fijado. En el proceso de esta fase, con el objeto de predecir probables futuros, se aplica la metodología prospectiva diseñada, que contempla el análisis del pasado y el presente, que determina los factores cuya influencia provocó el crecimiento en dimensiones de los grandes buques hasta la actualidad, y que constituye la base para emplear los métodos prospectivos que permiten determinar qué factores condicionarán en el futuro la evolución de los grandes buques. El probable escenario futuro formado por los factores determinados por el criterio experto, es validado mediante un modelo cuantitativo dinámico, que además de obtener el probable escenario futuro basado en las tendencias de comportamiento hasta el presente de los factores determinantes considerados, permite estudiar distintos probables escenarios futuros en función de considerar un cambio en la tendencia futura de los factores determinantes. El análisis del pasado indica que la tendencia al crecimiento de los grandes buques portacontenedores hasta el presente, se ha motivado por un crecimiento económico mundial que se tradujo en un aumento del comercio internacional, particularmente entre los países de Asia, con Europa y Estados Unidos. Esta tendencia se ha visto favorecida por el factor globalización y la acelerada evolución tecnológica que ha permitido superar los obstáculos que se presentaron. Es de destacar que aún en periodos de crisis económicas, con pronósticos de contracciones en el comercio, en los últimos años continuó la tendencia al crecimiento en dimensiones, en busca de una economía de escala para el transporte marítimo de contenedores, en las rutas transoceánicas. La investigación de la evolución de los grandes buques portacontenedores en el futuro, se efectúa mediante el empleo de una metodología prospectiva en la que el criterio experto se valida con un método cuantitativo dinámico, y además se fundamenta en una solida base pre-prospectiva. La metodología diseñada permite evaluar con un alto grado de objetividad cuales serán los condicionantes que incidirán en el crecimiento en tamaño de los grandes buques portacontenedores en el escenario con mayor probabilidad de acontecer en los próximos veinte años (2032), y también en otros escenarios que podrían presentarse en el caso de que los factores modifiquen su tendencia o bien se produzcan hechos aleatorios. El resultado se sintetiza en que la tendencia al crecimiento de los grandes buques portacontenedores en los próximos 20 años se verá condicionada por factores en relación a los conceptos de oferta (los que facilitan u obstaculizan la tendencia), demanda (los que motivan o impulsan la tendencia) y factores externos (los que desestabilizan el equilibrio entre oferta y demanda). La tendencia al crecimiento de los grandes buques portacontenedores se verá obstaculizada / limitada principalmente por factores relacionados a las infraestructuras, resultando los pasos y/o canales vinculados a las rutas marítimas, los limitantes futuros al crecimiento en dimensiones de los grandes buques portacontenedores; y la interacción buque / infraestructura (grúas) un factor que tenderá a obstaculizar esta tendencia de los grandes portacontenedores. El desarrollo económico mundial que estimula el comercio internacional y los factores precio del petróleo y condicionantes medioambientales impulsarán la tendencia al crecimiento de los grandes buques portacontenedores. Recent years have seen a sustained tendency towards the growth in the dimensions of large container ships. This has meant that port and other infrastructure used for container traffic has had to be adapted in order to provide the required services and to maintain a competitive position, so as not to lose market share. This situation implies the need for major investments in modifications to the container transport system, on account of the large volume of traffic to be handled in a short period of time. This in turn has generated a need to make provision for the probable future evolution of the ultimate dimensions that will be reached by large container ships. Such considerations give rise to the question of what are the future determinants for the growth of large container ships, requiring an overall vision of all the factors that will apply in future years, whether as a brake on or an incentive to the growth tendency which has been seen in the past and present In view of the fact that the theme to be dealt with and resolved relates to the future, with a forecasting horizon of some 20 years, a foresight methodology has been designed and applied so as to enable conclusions about probable future scenarios to be reached with a greater degree of objectivity. The designed methodology contains different methodological tools, both qualitative, semi-quantitative and quantitative, which are internally consistent. On the basis of past and present observations, the quantitative elements enable relationships to be established and forecasts to be made. Nevertheless such an approach loses validity more than three or four years into the future, on account of the very rapid and dynamic changes which may be seen at present in political, social and economic spheres. The semi-quantitative and qualitative methodologies are used coherently together and allow the analysis of past and present conditions, thus obtaining quantitative results which for short-term projections, which when integrated with the qualitative studies provide results for the long-term, facilitating the consideration of qualitative variables such as the increasing importance of environmental protection and the impact of piracy. The principal objective of the present thesis is "to identify the future conditions affecting the growth of large container ships and to determine possible scenarios". The thesis is structured in consecutive and related phases. The first three phases focus on the past and present in order to determine the problem to be resolved. The background is studied in order to establish the state of knowledge about the factors and circumstances which have motivated and facilitated the growth tendency for large container ships and the methodologies that have been used. In this way a specific foresight methodology is designed. The fourth phase, Results, is developed in distinct stages based on the previous phases, so as to resolve the problem posed and responding to the questions that arise. In this way the determined objective is reached. The fourth phase sees the application of the methodology that has been designed in order to predict posible futures. This includes analysis of the past and present factors which have caused the growth in the dimensions of large container ships up to the present. These provide the basis on which to apply the foresight methods which enable the future factors which will condition the development of such large container ships. The probable future scenarios are made up of the factors identified by expert judgement (using the Delphi technique) and validated by means of a dynamic quantitative model. This model both identifies the probable future scenarios based on past and present factors and enables the different future scenarios to be analysed as a function of future changes in the conditioning factors. Analysis of the past shows that the growth tendency up to the present for large container ships has been motivated by the growth of the world economy and the consequent increased international trade, especially between the countries of Asia with Europe and the United States. This tendency has been favoured by the trend towards globalization and by the rapid technical evolution in ship design, which has allowed the obstacles encountered to be overcome. It should be noted that even in periods of economic crisis, with an expectation for reduced trade, as experienced in recent years, the tendency towards increased ship dimensions has continued in search of economies of scale for the maritime transport of containers on transoceanic routes. The present investigation of the future evolution of large container ships has been done using a foresight methodology in which the expert judgement is validated by a dynamic quantitative methodology, founded on a firm pre-foresight analysis. The methodology that has been designed permits the evaluation, with a high degree of objectivity, of the future factors that will affect the growth of large container ships for the most probable scenario expected in the next 20 years (up to 2032). The evaluation applies also to other scenarios which may arise, in the event that their component factors are modified or indeed in the light of random events. In summary, the conclusión is that the tendency for growth in large container ships in the future 20 years will be determined by: factors related to supply, which slow or halt the tendency; factors related to demand, which encourage the tendency and finally, external factors which interrupt the equilibrium between supply and demand. The tendency for increasing growth in large container ships will be limited or even halted by factors related to infrastructure, including the natural and man-made straits and canals used by maritime transport. In addition the infrastructure required to serve such vessels both in port (including cranes and other equipment) and related transport, will tend to slow the growth tendency. The factors which will continue to encourage the tendency towards the growth of large container ships include world economic development, which stimulates international trade, and an increasing emphasis on environmental aspects.

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.