Treatment of lung infection in patients with cystic fibrosis:Current and future strategies

In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic therapy for the major pathogens in CF airways, including prophylaxis against infection, eradication of early infection, suppression of chronic infection, and the treatment of infective exacerbations. We outline measures to optimize maintenance treatment for infection in the light of novel antibiotic drug formulations. We discuss new developments in culture-independent microbiological diagnostic techniques and the use of tools for monitoring the success of antibiotic treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment in CF patients are discussed.

Flow due to multiple jets downstream of a barrage: Experiments, 3-D CFD and depth-averaged modelling

The flow through and downstream of a row of seven open draft tubes in a barrage has been investigated through laboratory experiments in a wide flume, a three-dimensional (3D) computational fluid dynamics simulation, and a two-dimensional depth-averaged computation. Agreement between the experiments and the 3D modeling is shown to be good, including the prediction of an asymmetric Coandă effect. One aim is to determine the distance downstream at which depth-averaged modeling provides a reasonable prediction; this is shown to be approximately 20 tube diameters downstream of the barrage. Upstream of this, the depth-averaged modeling inaccurately predicts water level, bed shear, and the 3D flow field. The 3D model shows that bed shear stress can be markedly magnified near the barrage, particularly where the jets become attached.

A Two Dimensional Experimental Investigation of Slamming of an Oscillating Wave Surge Converter

This paper describes a series of experiments undertaken to investigate the slamming of an Oscillating Wave Surge Converter in extreme sea states. These two-dimensional experiments were undertaken in the Wave Flume at Ecole Centrale Marseille. Images from a high speed camera are used to identify the physics of the slamming process. A single pressure sensor is used to record the characteristic of the pressure. Finally numerical results are compared to the output from the experiments.

Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial

BACKGROUND: Ivacaftor has been previously assessed in patients with cystic fibrosis with Gly551Asp-CFTR or other gating mutations. We assessed ivacaftor in patients with Arg117His-CFTR, a residual function mutation.

METHODS: We did a 24-week, placebo-controlled, double-blind, randomised clinical trial, which enrolled 69 patients with cystic fibrosis aged 6 years and older with Arg117His-CFTR and percentage of predicted forced expiratory volume in 1 s (% predicted FEV1) of at least 40. We randomly assigned eligible patients (1:1) to receive placebo or ivacaftor 150 mg every 12 h for 24 weeks. Randomisation was stratified by age (6-11, 12-17, and ≥18 years) and % predicted FEV1 (<70, ≥70 to ≤90, and >90). The primary outcome was the absolute change from baseline in % predicted FEV1 through week 24. Secondary outcomes included safety and changes in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain scores. An open-label extension enrolled 65 of the patients after washout; after 12 weeks, we did an interim analysis.

FINDINGS: After 24 weeks, the treatment difference in mean absolute change in % predicted FEV1 between ivacaftor (n=34) and placebo (n=35) was 2·1 percentage points (95% CI -1·13 to 5·35; p=0·20). Ivacaftor treatment resulted in significant treatment differences in sweat chloride (-24·0 mmol/L, 95% CI -28·01 to -19·93; p<0·0001) and CFQ-R respiratory domain (8·4, 2·17 to 14·61; p=0·009). In prespecified subgroup analyses, % predicted FEV1 significantly improved with ivacaftor in patients aged 18 years or older (treatment difference vs placebo: 5·0 percentage points, 95% CI 1·15 to 8·78; p=0·01), but not in patients aged 6-11 years (-6·3 percentage points, -11·96 to -0·71; p=0·03). In the extension study, both placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement (absolute change from post-washout baseline at week 12: placebo-to-ivacaftor, 5·0 percentage points [p=0·0005]; ivacaftor-to-ivacaftor, 6·0 percentage points [p=0·006]). We did not identify any new safety concerns. The studies are registered with ClinicalTrials.gov (the randomised, placebo-controlled study, number NCT01614457; the open-label extension study, number NCT01707290).

INTERPRETATION: Although this study did not show a significant improvement in % predicted FEV1, ivacaftor did significantly improve sweat chloride and CFQ-R respiratory domain scores and lung function in adult patients with Arg117His-CFTR, indicating that ivacaftor might benefit patients with Arg117His-CFTR who have established disease.

Properties of Hydraulic Jump over Apparent Corrugated Beds

The characteristics of hydraulic jumps were investigated for three shapes of artificial apparent corrugated beds in a horizontal rectangular flume. Rectangular, triangular, and circular-shaped tire waste corrugated beds were used. Froude number ranged from 2.75 to 4.25. The experimental observations included water surface profiles, bed shear stress, and the hydraulic jump length. Results showed that the shape of the corrugation had relatively insignificant effects on hydraulic jump properties for small Froude numbers. The rectangular, triangular, and circular-shaped corrugated beds reduced the hydraulic jump length by up to 7, 10, and 11%, respectively. The corrugated bed also reduced the tailwater depth by up to 11.5% compared with the smooth bed. The apparent conditions of corrugated bed reduced the hydraulic jump relative length and height by about 0.4 and 0.5, respectively. The circular-shaped tire waste was found to be more effective in reducing the length and depth of the hydraulic jump.

Biofilm Complexity Controls Fine Particle Dynamics in Streams

Most models of riverine eco-hydrology and biogeochemistry rely upon bulk parameterization of fluxes. However, the transport and retention of carbon and nutrients in headwater streams is strongly influenced by biofilms (surface-attached microbial communities), which results in strong feedbacks between stream hydrodynamics and biogeochemistry. Mechanistic understanding of the interactions between streambed biofilms and nutrient dynamics is lacking. Here we present experimental results linking microscale observations of biofilm community structure to the deposition and resuspension of clay-sized mineral particles in streams. Biofilms were grown in identical 3 m recirculating flumes over periods of 14-50 days. Fluorescent particles were introduced to each flume, and their deposition was traced over 30 minutes. Particle resuspension from the biofilms was then observed under an increased stream flow, mimicking a flood event. We quantified particle fluxes using flow cytometry and epifluorescence microscopy. We directly observed particle adhesion to the biofilm using a confocal laser scanning microscope. 3-D Optical Coherence Tomography was used to determine biofilm roughness, areal coverage and void space in each flume. These measurements allow us to link biofilm complexity to particle retention during both baseflow and floodflow. The results suggest that increased biofilm complexity favors deposition and retention of fine particles in streams.

Novel DGT method with tri-metal oxide adsorbent for in situ spatiotemporal flux measurement of fluoride in waters and sediments

Natural mineral-water interface reactions drive ecosystem/global fluoride (F−) cycling. These small-scale processes prove challenging to monitoring due to mobilization being highly localized and variable; influenced by changing climate, hydrology, dissolution chemistries and pedogenosis. These release events could be captured in situ by the passive sampling technique, diffusive gradients in thin-films (DGT), providing a cost-effective and time-integrated measurement of F− mobilization. However, attempts to develop the method for F− have been unsuccessful due to the very restrictive operational ranges that most F−-absorbents function within. A new hybrid-DGT technique for F− quantification containing a three-phase fine particle composite (Fesingle bondAlsingle bondCe, FAC) adsorbent was developed and evaluated. Sampler response was validated in laboratory and field deployments, passing solution chemistry QC within ionic strength and pH ranges of 0–200 mmol L−1 and 4.3–9.1, respectively, and exhibiting high sorption capacities (98 ± 8 μg cm−2). FAC-DGT measurements adequately predicted up to weeklong averaged in situ F− fluvial fluxes in a freshwater river and F− concentrations in a wastewater treatment flume determined by high frequency active sampling. While, millimetre-scale diffusive fluxes across the sediment-water interface were modeled for three contrasting lake bed sediments from a F−-enriched lake using the new FAC-DGT platform.

Utilização de técnicas de análise fotogramétricas em quebra-mares de taludes

Dissertação de Natureza Científica elaborada no Laboratório Nacional de Engenharia Civil (LNEC) para obtenção do grau de mestre em Engenharia Civil na Área de Especialização de Hidráulica no âmbito do protocolo de cooperação entre o ISEL e o LNEC

Second Welland Canal - Book 2, Survey Map 11 - Marlatts Bridge in Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in Thorold Township. Identified structures associated with the Canal include the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads(ex. Road to Allanburgh), Marlatt's Bridge, Marlatt's Culvert, Marlatt's Dwelling House, Willson's Dwelling House, Willson's Tannery, a flume, a bridge house, a covered drain, and a creek. Properties and property owners of note are: Lots 49, 50, and 51, Hiram Marlatt, Willson, John Kelley, and E. Hopkins.

Second Welland Canal - Book 2, Survey Map 12 - Through Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in Thorold Township. Identified structures associated with the Canal include the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Road to Allanburgh), Higgins Flume, Spoil Bank, a creek, a pond, a culvert, and a barn. Properties and property owners of note are: Lots 73, 74, and 75, G. Keefer Sr., James Gibson, Malum Swayze, Henry Higgins, S. Merithew, and Robert Smith.

Second Welland Canal - Book 2, Survey Map 13 - Through Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in Thorold Township northwest of Allanburgh. Identified structures associated with the Canal include the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Holland Road), Higgins Flume, Davis Culvert, J. Upper Tavern, a barn, creek, bridge, ditch, fence, and several unnamed ponds. Properties and property owners of note are: Lots 96, 97, and 98, Joseph Upper, A. Church, and T. Higgins.

Second Welland Canal - Book 3, Survey Map 12 - Village of Welland

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in the Village of Welland. Identified structures and features associated with the Canal include the towing path, the old canal, the aqueduct lock, the new aqueduct, the old aqueduct, Lock Tenders House, a waste weir, culvert, covered drain, drain, dam, flume, and the canal's New Line. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include bridges, roads, and streets (ex. Division Street and Main Street), Chippewa Creek, Mill Pond, Mill Race, Court House and Gaol, Seeley (Seely) and Dunlop Saw Mill, Seeley (Seely) and Dunlop (Burnt) Grist Mill, Montrose Grist Mill, M. Caferty (Cafferty) City Hotel, Welland House by Wilkerson, Eli Mead Wharf Lot, A. Sherwood Wharf Lot, D. P. Myers Store, M. Cook Grist Mill, A. H. Cosby Saw Mill, Betts Lumber Yard, T. Quinn Tavern, a Carding Mill, shed, several barns, a hotel, and several structures or properties belonging to: J. P Evans, W. A. Phillips, S. Hampton, M. Silverthorne, D. McEwing, W. B. Hendershott (Hendershot), T. Burgar, J. Brookfield, A. Hendershott, Joseph Burgar, C. Demrie, M. Cafferty, J. Spencer, Mrs. Curran, John Lemon, D. Cooper, H. A. Rose, J. Bridges, A. Chapman, and R. Morewood. A structure belonging to a D. McKelly or McKully, and a store belonging to a J. Fino or Finn are also present. Properties and property owners of note are: Lots 247 and 248 of the Thorold Township, 5th Concession Lots 26 and 25 of the Crowland Township, Smith Shotwell, Eli Mead, D. P Myers, Donaldson, McFarland, Mrs. Silverthorne, Price, and Griffth. A County Court House Lot containing the Court House, Gaol and Gaol Yard is present.

Caractérisation de la dynamique des berges de deux tributaires contrastés du Saint-Laurent : le cas des rivières Batiscan et Saint-François

L’érosion des berges est un processus clé de la dynamique fluviale. Elle influence considérablement la charge sédimentaire des rivières et contrôle l’évolution latérale des chenaux. Les méthodes de caractérisation des mécanismes et des variables affectant l’érosion des berges sont toutefois imprécises et difficiles à appliquer. Ce projet a pour objectif de caractériser la dynamique actuelle des berges de deux tributaires contrastés du Saint-Laurent : les rivières Saint-François et Batiscan. Le premier objectif vise à quantifier les caractéristiques géotechniques de deux tronçons des rivières à l’étude près de l’embouchure avec le Saint-Laurent en décrivant la stratigraphie à différents sites typiques et en recueillant des échantillons de sédiments afin de mesurer différentes variables géotechniques (granulométrie, limites d’Atterberg, résistance à l’érosion mécanique, résistance à l’érosion fluviale). Le second objectif vise à quantifier les principales caractéristiques hydrodynamiques (précipitations, débits, cisaillements, vitesses) des deux sections de rivière. Le troisième et dernier objectif cherche à mesurer les taux d’érosion à l’échelle saisonnière en utilisant des relevés GPS et des chaînes d’érosion et à identifier les mécanismes d’érosion qui opèrent sur les rivières. Les résultats montrent une érosion importante des berges sur chacun des tributaires, mais les mécanismes qui la cause diffèrent. La Batiscan possède des berges dont le matériel est cohésif et ses berges sont principalement marquées par des ruptures de masse. La Saint-François présente des berges peu cohésives ce qui favorise l’érosion fluviale. Le taux de recul sur la rivière Saint-François est de l’ordre de 1 à 3 m/an dans certaines sections de la rivière. Une nouvelle méthode de mesure du cisaillement critique d’érosion fluviale à l’aide d’un chenal expérimental a été élaborée. Les cisaillements critiques obtenus se situent entre 1,19 et 13,41 Pa. Les résultats montrent que les facteurs jouant sur l’érosion des berges ont une variabilité intrinsèque et systémique difficile à mesurer. Le protocole expérimental développé dans ce projet s’est toutefois avéré utile pour étudier les principales variables qui influencent l’érosion des berges, tout en quantifiant les taux d’érosion et les mécanismes d’érosion de berge de deux tributaires importants du fleuve Saint-Laurent. Ce protocole pourrait être utile dans d’autres contextes.

Habitat variability and the individual variability of juvenile Atlantic salmon (Salmo salar)

La variabilité spatiale et temporelle de l’écoulement en rivière contribue à créer une mosaïque d’habitat dynamique qui soutient la diversité écologique. Une des questions fondamentales en écohydraulique est de déterminer quelles sont les échelles spatiales et temporelles de variation de l’habitat les plus importantes pour les organismes à divers stades de vie. L’objectif général de la thèse consiste à examiner les liens entre la variabilité de l’habitat et le comportement du saumon Atlantique juvénile. Plus spécifiquement, trois thèmes sont abordés : la turbulence en tant que variable d’habitat du poisson, les échelles spatiales et temporelles de sélection de l’habitat et la variabilité individuelle du comportement du poisson. À l’aide de données empiriques détaillées et d’analyses statistiques variées, nos objectifs étaient de 1) quantifier les liens causaux entre les variables d’habitat du poisson « usuelles » et les propriétés turbulentes à échelles multiples; 2) tester l’utilisation d’un chenal portatif pour analyser l’effet des propriétés turbulentes sur les probabilités de capture de proie et du comportement alimentaire des saumons juvéniles; 3) analyser les échelles spatiales et temporelles de sélection de l’habitat dans un tronçon l’été et l’automne; 4) examiner la variation individuelle saisonnière et journalière des patrons d’activité, d’utilisation de l’habitat et de leur interaction; 5) investiguer la variation individuelle du comportement spatial en relation aux fluctuations environnementales. La thèse procure une caractérisation détaillée de la turbulence dans les mouilles et les seuils et montre que la capacité des variables d’habitat du poisson usuelles à expliquer les propriétés turbulentes est relativement basse, surtout dans les petites échelles, mais varie de façon importante entre les unités morphologiques. D’un point de vue pratique, ce niveau de complexité suggère que la turbulence devrait être considérée comme une variable écologique distincte. Dans une deuxième expérience, en utilisant un chenal portatif in situ, nous n’avons pas confirmé de façon concluante, ni écarté l’effet de la turbulence sur la probabilité de capture des proies, mais avons observé une sélection préférentielle de localisations où la turbulence était relativement faible. La sélection d’habitats de faible turbulence a aussi été observée en conditions naturelles dans une étude basée sur des observations pour laquelle 66 poissons ont été marqués à l’aide de transpondeurs passifs et suivis pendant trois mois dans un tronçon de rivière à l’aide d’un réseau d’antennes enfouies dans le lit. La sélection de l’habitat était dépendante de l’échelle d’observation. Les poissons étaient associés aux profondeurs modérées à micro-échelle, mais aussi à des profondeurs plus élevées à l’échelle des patchs. De plus, l’étendue d’habitats utilisés a augmenté de façon asymptotique avec l’échelle temporelle. L’échelle d’une heure a été considérée comme optimale pour décrire l’habitat utilisé dans une journée et l’échelle de trois jours pour décrire l’habitat utilisé dans un mois. Le suivi individuel a révélé une forte variabilité inter-individuelle des patrons d’activité, certains individus étant principalement nocturnes alors que d’autres ont fréquemment changé de patrons d’activité. Les changements de patrons d’activité étaient liés aux variables environnementales, mais aussi à l’utilisation de l’habitat des individus, ce qui pourrait signifier que l’utilisation d’habitats suboptimaux engendre la nécessité d’augmenter l’activité diurne, quand l’apport alimentaire et le risque de prédation sont plus élevés. La variabilité inter-individuelle élevée a aussi été observée dans le comportement spatial. La plupart des poissons ont présenté une faible mobilité la plupart des jours, mais ont occasionnellement effectué des mouvements de forte amplitude. En fait, la variabilité inter-individuelle a compté pour seulement 12-17% de la variabilité totale de la mobilité des poissons. Ces résultats questionnent la prémisse que la population soit composée de fractions d’individus sédentaires et mobiles. La variation individuelle journalière suggère que la mobilité est une réponse à des changements des conditions plutôt qu’à un trait de comportement individuel.

Tamizaje neonatal para fibrosis quística en una muestra de la ciudad de Bogotá

La Fibrosis Quística es la enfermedad autosómica recesiva mas frecuente en caucásicos. En Colombia no se conoce la incidencia de la enfermedad, pero investigaciones del grupo de la Universidad del Rosario indican que podría ser relativamente alta. Objetivo: Determinar la incidencia de afectados por Fibrosis Quística en una muestra de recién nacidos de la ciudad de Bogotá. Metodología: Se analizan 8.297 muestras de sangre de cordón umbilical y se comparan tres protocolos de tamizaje neonatal: TIR/TIR, TIR/DNA y TIR/DNA/TIR. Resultados: El presente trabajo muestra una incidencia de 1 en 8.297 afectados en la muestra analizada. Conclusiones: Dada la relativamente alta incidencia demostrada en Bogotá, se justifica la implementación de Tamizaje Neonatal para Fibrosis Quística en Colombia.