Cirugía y radioembolización de tumores hepáticos / Surgery and radioembolization of liver tumors

La resección quirúrgica se considera el tratamiento curativo por excelencia para los pacientes con tumores hepáticos primarios o metastásicos. Sin embargo, menos de 40% de ellos son candidatos a cirugía, ya sea por factores no modificables (comorbilidades, edad, disfunción hepática…), como por la invasión o proximidad del tumor a los principales pedículos vasculares, la falta de un futuro remanente hepático (FRH) adecuado para mantener una función hepática postoperatoria, o criterios de tamaño y numero tumoral. En estos últimos factores, la radioembolización hepática ha mostrado tener un papel como herramienta prequirúrgica, ya sea mediante la hipertrofia del FRH o mediante la reducción del tamaño tumoral que consigue disminuir la estadificación tumoral (término conocido como «downstaging»). A estos se suma un tercer factor, que es su capacidad de aplicar el test del tiempo, que permite identificar aquellos pacientes que presenten en un plazo corto de tiempo progresión de la enfermedad (tanto a nivel local como a distancia), evitándoles una cirugía innecesaria. En este trabajo se pretende hacer una revisión de la radioembolización como herramienta facilitadora de la cirugía hepática, tanto a través de la experiencia de nuestro centro como de la evidencia científica disponible (AU)

Surgical resection is considered the curative treatment par excellence for patients with primary or metastatic liver tumors. However, less than 40% of them are candidates for surgery, either due to non-modifiable factors (comorbidities, age, liver dysfunction...), or to the invasion or proximity of the tumor to the main vascular requirements, the lack of a future liver remnant (FLR) adequate to maintain postoperative liver function, or criteria of tumor size and number. In these last factors, hepatic radioembolization has been shown to play a role as a presurgical tool, either by hypertrophy of the FLR or by reducing tumor size that manages to reduce tumor staging (term known as “downstaging”). To these is added a third factor, which is its ability to apply the test of time, which makes it possible to identify those patients who present progression of the disease in a short period of time (both locally and at distance), avoiding a unnecessary surgery. This paper aims to review RE as a tool to facilitate liver surgery, both through the experience of our center and the available scientific evidence (AU)

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain

Fundamento. La precisión diagnóstica de la gammagrafía ósea (GO) aumenta con las imágenes SPECT/TAC haciendo conveniente reevaluar su utilidad diagnóstica en la sacroilitis de la espondiloartritis axial (EA). El objetivo fue comparar el rendimiento diagnóstico de la resonancia magnética (RM), la SPECT/TC y ambas pruebas combinadas, y evaluar la correlación entre los índices cuantitativos de ambas técnicas. Métodos. A 31 pacientes con EA activa y 22 con lumbalgia inflamatoria se les realizó una RM y una SPECT/TC de las articulaciones sacroilíacas y se calculó la precisión diagnóstica de ambas técnicas respecto al diagnóstico clínico. La correlación entre ambas pruebas se calculó comparando los índices de actividad del SPECT/TC con los sistemas de puntuación Berlín y SPARCC de RM. Resultados. Los valores de sensibilidad y especificidad de la SPECT/TC cuantitativa, tomando como punto de corte el cociente sacroilíaca/promontorio >1,36, fueron similares a los publicados para la RM. La combinación de ambas técnicas aumentó la sensibilidad manteniendo una alta especificidad. La correlación entre las escalas totales de RM y SPECT/TC fue moderada y mejoraba al utilizar únicamente las escalas de inflamación. Conclusiones. La SPECT/TC cuantitativa muestra una mejor precisión diagnóstica que la GO planar en la sacroilitis activa y una correlación moderada con las puntuaciones de RM. La combinación de ambas técnicas aumenta la precisión diagnóstica. Por tanto, la SPECT/TAC cuantitativa podría tener un papel relevante en el diagnóstico de sacroilitis en pacientes con alta sospecha de EA y RM negativa/no concluyente o en aquellos pacientes en los que no se pueda realizar una RM.(AU)

Background. The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacroiliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. Methods. Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. Results. The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. Conclusion. Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quantitative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.(AU)

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain.

BACKGROUND: The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacro-iliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. METHODS: Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. RESULTS: The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. CONCLUSION: Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quanti-tative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.

Detection of new biohints on lichens with Raman spectroscopy after space- and Mars like conditions exposure: Mission Ground Reference (MGR) samples.

The extremophile lichen Circinaria gyrosa (C. gyrosa) is one of the selected species within the BIOMEX (Biology and Mars Experiment) experiment. Here we present the Raman study of a biohint found in this lichen, called whewellite (calcium oxalate monohydrate), and other organic compounds and mineral products of the biological activity of the astrobiologically relevant model system C. gyrosa. Samples were exposed to space- and simulated Mars-like conditions during the EXPOSE-R2 mission parallel ground reference experiment MGR performed at the space- and planetary chambers of DLR-Cologne to study Mars' habitability and resistance to real space conditions. In this work, we complete the information of natural C. gyrosa about the process of diagenesis by the identification of carbonate crystals in the inner medulla together with the biomineral whewellite. The analysis by Raman spectroscopy of simulated Space and Mars exposed samples confirm alterations and damages of the photobiont part of the lichen and changes related to the molecular structure of whewellite. The conclusions of this work will be important to understand what are the effects to consider when biological systems are exposed to space or Mars-like conditions and to expand our knowledge of how life survives in most extreme conditions that is a prerequisite in future planetary exploration projects.

Diagnostic accuracy of visual analysis versus dual time-point imaging with 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules with low uptake. / Precisión diagnóstica del análisis visual frente al protocolo de imagen tardía con 18F-FDG PET/TC para la caracterización de nódulos pulmonares indeterminados con baja captación.

OBJECTIVE: To determine the accuracy of visual analysis and the retention index (RI) with dual-time point 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules (IPN) with low FDG uptake. MATERIALS AND METHODS: A retrospective analysis was performed on 43 patients (28 men, 64 ± 11 years old, range 36-83 years) referred for IPN characterization with 18F-FDG-PET/CT and maximum standard uptake value ≤ 2.5 at 60 minutes post-injection (SUVmax1). Nodules were analyzed by size, visual score for FDG uptake on standard (OSEM 2,8) and high definition (HD) reconstructions, SUVmax1, SUVmax at 180 minutes post-injection (SUVmax2), and RI was calculated. The definitive diagnosis was based on histopathological confirmation (n = 28) or ≥ 2 years of follow-up. RESULTS: Twenty-four (56%) nodules were malignant. RI ≥ 10% on standard reconstruction detected 18 nodules that would have been considered negative using the standard SUVmax ≥ 2.5 criterion for malignancy. RI ≥ 10% had a sensitivity, specificity, PPV, NPV and accuracy of 75, 73.7, 78.3, 70, and 74.4%, respectively, while for FDG uptake > liver on HD these were 79.1, 63.2, 73.1, 70.6, and 72.1%, respectively. SUVmax1 ≥ 2, SUVmax2 > 2.5 and FDG uptake > liver on standard reconstruction had a PPV of 100%. FDG uptake > mediastinum on HD had a NPV of 100%. CONCLUSIONS: RI ≥ 10% was the most accurate criterion for malignancy, followed by FDG uptake > liver on HD reconstruction. On standard reconstruction, SUVmax1 ≥2 was highly predictive of malignancy, as well as SUVmax2 > 2.5 and FDG uptake > liver. FDG uptake < mediastinum on HD was highly predictive of benign nodules.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Enhances Hippocampal Synaptic Plasticity and Improves Memory Performance in Huntington's Disease.

Deficits in hippocampal synaptic plasticity result in cognitive impairment in Huntington's disease (HD). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts neuroprotective actions, mainly through the PAC1 receptor. However, the role of PACAP in cognition is poorly understood, and no data exists in the context of Huntington's disease (HD). Here, we investigated the ability of PACAP receptor stimulation to enhance memory development in HD. First, we observed a hippocampal decline of all three PACAP receptor expressions, i.e., PAC1, VPAC1, and VPAC2, in two different HD mouse models, R6/1 and HdhQ7/Q111, from the onset of cognitive dysfunction. In hippocampal post-mortem human samples, we found a specific decrease of PAC1, without changes in VPAC1 and VPAC2 receptors. To determine whether activation of PACAP receptors could contribute to improve memory performance, we conducted daily intranasal administration of PACAP38 to R6/1 mice at the onset of cognitive impairment for seven days. We found that PACAP treatment rescued PAC1 level in R6/1 mice, promoted expression of the hippocampal brain-derived neurotrophic factor, and reduced the formation of mutant huntingtin aggregates. Furthermore, PACAP administration counteracted R6/1 mice memory deficits as analyzed by the novel object recognition test and the T-maze spontaneous alternation task. Importantly, the effect of PACAP on cognitive performance was associated with an increase of VGlut-1 and PSD95 immunolabeling in hippocampus of R6/1 mice. Taken together, these results suggest that PACAP, acting through stimulation of PAC1 receptor, may have a therapeutic potential to counteract cognitive deficits induced in HD.

Analysis of the stability of high-solids anaerobic digestion of agro-industrial waste and sewage sludge.

The pilot-scale high-solids anaerobic digestion (HS-AD) of agro-industrial wastes and sewage sludge was analysed in terms of stability by monitoring the most common parameters used to check the performance of anaerobic digesters, i.e. Volatile Fatty Acids (VFA), ammonia nitrogen, pH, alkalinity and methane production. The results reflected similar evolution for the parameters analysed, except for an experiment that presented an unsuccessful start-up. The rest of the experiments ran successfully, although the threshold values proposed in the literature for the detection of an imbalance in wet processes were exceeded, proving the versatility of HS-AD to treat different wastes. The results evidence the need for understanding the dynamics of a high-solids system so as to detect periods of imbalance and to determine inhibitory levels for different compounds formed during anaerobic decomposition. Moreover, the findings presented here could be useful in developing an experimental basis to construct new control strategies for HS-AD.

Extremotolerance and resistance of lichens: comparative studies on five species used in astrobiological research I. Morphological and anatomical characteristics.

Lichens are symbioses of two organisms, a fungal mycobiont and a photoautotrophic photobiont. In nature, many lichens tolerate extreme environmental conditions and thus became valuable models in astrobiological research to fathom biological resistance towards non-terrestrial conditions; including space exposure, hypervelocity impact simulations as well as space and Martian parameter simulations. All studies demonstrated the high resistance towards non-terrestrial abiotic factors of selected extremotolerant lichens. Besides other adaptations, this study focuses on the morphological and anatomical traits by comparing five lichen species-Circinaria gyrosa, Rhizocarpon geographicum, Xanthoria elegans, Buellia frigida, Pleopsidium chlorophanum-used in present-day astrobiological research. Detailed investigation of thallus organization by microscopy methods allows to study the effect of morphology on lichen resistance and forms a basis for interpreting data of recent and future experiments. All investigated lichens reveal a common heteromerous thallus structure but diverging sets of morphological-anatomical traits, as intra-/extra-thalline mucilage matrices, cortices, algal arrangements, and hyphal strands. In B. frigida, R. geographicum, and X. elegans the combination of pigmented cortex, algal arrangement, and mucilage seems to enhance resistance, while subcortex and algal clustering seem to be crucial in C. gyrosa, as well as pigmented cortices and basal thallus protrusions in P. chlorophanum. Thus, generalizations on morphologically conferred resistance have to be avoided. Such differences might reflect the diverging evolutionary histories and are advantageous by adapting lichens to prevalent abiotic stressors. The peculiar lichen morphology demonstrates its remarkable stake in resisting extreme terrestrial conditions and may explain the high resistance of lichens found in astrobiological research.

Ecophysiology and genetic structure of polar versus temperate populations of the lichen Cetraria aculeata.

We studied polar and temperate samples of the lichen Cetraria aculeata to investigate whether genetical differences between photobionts are correlated with physiological properties of the lichen holobiont. Net photosynthesis and dark respiration (DR) at different temperatures (from 0 to 30 °C) and photon flux densities (from 0 to 1,200 µmol m(-2) s(-1)) were studied for four populations of Cetraria aculeata. Samples were collected from maritime Antarctica, Svalbard, Germany and Spain, representing different climatic situations. Sequencing of the photobiont showed that the investigated samples fall in the polar and temperate clade described in Fernández-Mendoza et al. (Mol Ecol 20:1208-1232, 2011). Lichens with photobionts from these clades differ in their temperature optimum for photosynthesis, maximal net photosynthesis, maximal DR and chlorophyll content. Maximal net photosynthesis was much lower in Antarctica and Svalbard than in Germany and Spain. The difference was smaller when rates were expressed by chlorophyll content. The same is true for the temperature optima of polar (11 °C) and temperate (15 and 17 °C) lichens. Our results indicate that lichen mycobionts may adapt or acclimate to local environmental conditions either by selecting algae from regional pools or by regulating algal cell numbers (chlorophyll content) within the thallus.

Diversity of endosymbiotic Nostoc in Gunnera magellanica from Tierra del Fuego, Chile [corrected].

Global warming is causing ice retreat in glaciers worldwide, most visibly over the last few decades in some areas of the planet. One of the most affected areas is the region of Tierra del Fuego (southern South America). Vascular plant recolonisation of recently deglaciated areas in this region is initiated by Gunnera magellanica, which forms symbiotic associations with the cyanobacterial genus Nostoc, a trait that likely confers advantages in this colonisation process. This symbiotic association in the genus Gunnera is notable as it represents the only known symbiotic relationship between angiosperms and cyanobacteria. The aim of this work was to study the genetic diversity of the Nostoc symbionts in Gunnera at three different, nested scale levels: specimen, population and region. Three different genomic regions were examined in the study: a fragment of the small subunit ribosomal RNA gene (16S), the RuBisCO large subunit gene coupled with its promoter sequence and a chaperon-like protein (rbcLX) and the ribosomal internal transcribed spacer (ITS) region. The identity of Nostoc as the symbiont was confirmed in all the infected rhizome tissue analysed. Strains isolated in the present study were closely related to strains known to form symbioses with other organisms, such as lichen-forming fungi or bryophytes. We found 12 unique haplotypes in the 16S rRNA (small subunit) region analysis, 19 unique haplotypes in the ITS region analysis and 57 in the RuBisCO proteins region (rbcLX). No genetic variability was found among Nostoc symbionts within a single host plant while Nostoc populations among different host plants within a given sampling site revealed major differences. Noteworthy, interpopulation variation was also shown between recently deglaciated soils and more ancient ones, between eastern and western sites and between northern and southern slopes of Cordillera Darwin. The cell structure of the symbiotic relationship was observed with low-temperature scanning electron microscopy, showing changes in morphology of both cyanobiont cells (differentiate more heterocysts) and plant cells (increased size). Developmental stages of the symbiosis, including cell walls and membranes and EPS matrix states, were also observed.

Tuberculosis diagnosis after bleach processing for early stage tuberculosis laboratory capacity building.

The diagnosis of tuberculosis is seriously hampered in the absence of standard biosafety laboratory facilities for specimen concentration and Mycobacterium tuberculosis culture. Within a laboratory twinning arrangement, heat-fixed direct smear and sediment from 74 bleach-processed and 20 non-processed specimens from Cumura Hospital, Guinea-Bissau, were sent to Lisbon for molecular evaluation of rifampicin resistance. Sequence analysis of a 369 base-pair rpoB locus detected 3.2% (3/94) resistant specimens. To our knowledge, this represents the first report on the molecular analysis of M. tuberculosis from bleach-processed sputum, an alternative to current diagnostic practice in low-resource settings.

Water network cost optimization in a paper mill based on a new library of mathematical models.

The increasing costs associated with water supply and the disposal of wastewater has stimulated industries to seek more efficient water management systems. Mathematical modelling and simulation can be a very valuable tool for the study of the multiple alternatives available whilst assessing optimum solutions for water management in industry. This study introduces a new steady state model library able to reproduce industrial water circuits. It has been implemented in a novel software framework for the representation, simulation and optimization of industrial water networks. A water circuit representing a paper mill has been modelled and simulated showing the capability to reproduce real case studies. Alternative scenarios for the water network have also been tested to assess the capability of the models to optimize water circuits minimizing total cost.

Influence of electrical stimulation on 3D-cultures of adipose tissue derived progenitor cells (ATDPCs) behavior.

Tissue engineering has a fundamental role in regenerative medicine. Still today, the major motivation for cardiac regeneration is to design a platform that enables the complete tissue structure and physiological function regeneration of injured myocardium areas. Although tissue engineering approaches have been generally developed for two-dimensional (2D) culture systems, three-dimensional (3D) systems are being spotlighted as the means to mimic better in vivo cellular conditions. This manuscript examines the influence of electrical stimulation on 3D cultures of adipose tissue-derived progenitor cells (ATDPCs). ATDPCs cells were encapsulated into a self-assembling peptide nanoscaffold (RAD16-I) and continuously electro stimulated during 14-20 days with 2-ms pulses of 50mV/cm at a frequency of 1 Hz. Good cellular network formation and construct diameter reduction was observed in electro stimulated samples. Importantly, the process of electro stimulation does not disrupt cell viability or connectivity. As a future outlook, differentiation studies to cardiomyocytes-like cells will be performed analyzing gene profile and protein expression.

A knowledge-based control system for air-scour optimisation in membrane bioreactors.

Although membrane bioreactors (MBRs) technology is still a growing sector, its progressive implementation all over the world, together with great technical achievements, has allowed it to reach a mature degree, just comparable to other more conventional wastewater treatment technologies. With current energy requirements around 0.6-1.1 kWh/m3 of treated wastewater and investment costs similar to conventional treatment plants, main market niche for MBRs can be areas with very high restrictive discharge limits, where treatment plants have to be compact or where water reuse is necessary. Operational costs are higher than for conventional treatments; consequently there is still a need and possibilities for energy saving and optimisation. This paper presents the development of a knowledge-based decision support system (DSS) for the integrated operation and remote control of the biological and physical (filtration and backwashing or relaxation) processes in MBRs. The core of the DSS is a knowledge-based control module for air-scour consumption automation and energy consumption minimisation.

Whole lichen thalli survive exposure to space conditions: results of Lithopanspermia experiment with Aspicilia fruticulosa.

The Lithopanspermia space experiment was launched in 2007 with the European Biopan facility for a 10-day spaceflight on board a Russian Foton retrievable satellite. Lithopanspermia included for the first time the vagrant lichen species Aspicilia fruticulosa from Guadalajara steppic highlands (Central Spain), as well as other lichen species. During spaceflight, the samples were exposed to selected space conditions, that is, the space vacuum, cosmic radiation, and different spectral ranges of solar radiation (λ ≥ 110, ≥200, ≥290, or ≥400 nm, respectively). After retrieval, the algal and fungal metabolic integrity of the samples were evaluated in terms of chlorophyll a fluorescence, ultrastructure, and CO(2) exchange rates. Whereas the space vacuum and cosmic radiation did not impair the metabolic activity of the lichens, solar electromagnetic radiation, especially in the wavelength range between 100 and 200 nm, caused reduced chlorophyll a yield fluorescence; however, there was a complete recovery after 72 h of reactivation. All samples showed positive rates of net photosynthesis and dark respiration in the gas exchange experiment. Although the ultrastructure of all flight samples showed some probable stress-induced changes (such as the presence of electron-dense bodies in cytoplasmic vacuoles and between the chloroplast thylakoids in photobiont cells as well as in cytoplasmic vacuoles of the mycobiont cells), we concluded that A. fruticulosa was capable of repairing all space-induced damage. Due to size limitations within the Lithopanspermia hardware, the possibility for replication on the sun-exposed samples was limited, and these first results on the resistance of the lichen symbiosis A. fruticulosa to space conditions and, in particular, on the spectral effectiveness of solar extraterrestrial radiation must be considered preliminary. Further testing in space and under space-simulated conditions will be required. Results of this study indicate that the quest to discern the limits of lichen symbiosis resistance to extreme environmental conditions remains open.

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children.

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal.

Knowledge-based system for automatic MBR control.

MBR technology is currently challenging traditional wastewater treatment systems and is increasingly selected for WWTP upgrading. MBR systems typically are constructed on a smaller footprint, and provide superior treated water quality. However, the main drawback of MBR technology is that the permeability of membranes declines during filtration due to membrane fouling, which for a large part causes the high aeration requirements of an MBR to counteract this fouling phenomenon. Due to the complex and still unknown mechanisms of membrane fouling it is neither possible to describe clearly its development by means of a deterministic model, nor to control it with a purely mathematical law. Consequently the majority of MBR applications are controlled in an "open-loop" way i.e. with predefined and fixed air scour and filtration/relaxation or backwashing cycles, and scheduled inline or offline chemical cleaning as a preventive measure, without taking into account the real needs of membrane cleaning based on its filtration performance. However, existing theoretical and empirical knowledge about potential cause-effect relations between a number of factors (influent characteristics, biomass characteristics and operational conditions) and MBR operation can be used to build a knowledge-based decision support system (KB-DSS) for the automatic control of MBRs. This KB-DSS contains a knowledge-based control module, which, based on real time comparison of the current permeability trend with "reference trends", aims at optimizing the operation and energy costs and decreasing fouling rates. In practice the automatic control system proposed regulates the set points of the key operational variables controlled in MBR systems (permeate flux, relaxation and backwash times, backwash flows and times, aeration flow rates, chemical cleaning frequency, waste sludge flow rate and recycle flow rates) and identifies its optimal value. This paper describes the concepts and the 3-level architecture of the knowledge-based DSS and details the knowledge-based control module. Preliminary results of the application of the control module to regulate the air flow rate of an MBR working with variable flux demonstrates the usefulness of this approach.

Responsiveness to stimuli of bispectral index, middle latency auditory evoked potentials and clinical scales in critically ill children.

SUMMARY: We performed simultaneous recordings of Bispectral Index (BIS) and middle latency auditory evoked potentials. We also recorded two clinical scales, the Modified Ramsay scale and the COMFORT scale. Heart rate and blood pressure were measured once a day, for a maximum of 5 days, in 81 critically ill children. Changes with tactile, auditory, and painful stimuli were analysed. All the stimuli significantly increased the BIS value, the painful stimulus having the greatest effect. The painful stimulus was the only one that altered the middle latency auditory evoked potentials. Although the responses of the clinical scales to stimuli were statistically significant, they were of little clinical relevance. None of the stimuli used significantly altered the heart rate or blood pressure. We conclude that tactile, auditory and painful stimuli produced changes of little relevance in the clinical scales, BIS or middle latency auditory evoked potentials. We found the BIS was the most sensitive method and the painful stimulus had the greatest effect.

The effect of operational parameters of the process of sludge ozonation on the solubilisation of organic and nitrogenous compounds.

An evaluation of various operational parameters on the process of sludge ozonation was carried out based on semi-batch experiments. Particular reference has been given to examine the main parameters affecting the solubilisation of organic matter and nitrogenous compounds. Various sets of experiments were undertaken using real sewage sludge to feed a semi-industrial ozonation plant. Applying ozone dosages between 25 and 35 mg O(3)/gTSS, the organic matter solubilisation obtained through ozonation increases proportionally to ozone dosage until a maximum value of 430 mg COD/L. Concerning the nitrogenous compounds, no variation in nitrite concentration and a low increase in nitrate concentration were attained, regardless of the applied ozone dosage. Little increase in ammonia concentration was achieved for low ozone dosages, whilst applying dosages higher than 20 mg O(3)/gTSS, the variation of ammonia increased proportionally with ozone dosage. Experiments using hydraulic retention time (HRT) between 10 and 60 min resulted in a similar COD solubilisation, confirming a rapid rate of cell lysis during ozonation of sludge.

Mass and charge conservation check in dynamic models: application to the new ADM1 model.

This paper proposes a systematic methodology for the analysis of the mass and charge balances in dynamic models expressed using the Petersen matrix notation. This methodology is based on the definition of the model components via elemental mass fractions and in the estimation of the COD as a function of the redox equations associated with these elements. This approach makes the automatic calculation of all the stoichiometric coefficients under different measuring units and the study of COD, charge or mass fluxes easier. As an example of its application this methodology was applied to the ADM1 in order to illustrate its usefulness for the analysis of organic matter characterisation, nitrogen release or biogas composition in anaerobic digestion. The application of the methodology for a rigorous integration of different IWA models is proposed for further study.