Development of Self-Cleaning Box Culvert Designs, TR-545, 2009

The main function of a roadway culvert is to effectively convey drainage flow during normal and extreme hydrologic conditions. This function is often impaired due to the sedimentation blockage of the culvert. This research sought to understand the mechanics of sedimentation process at multi-box culverts, and develop self-cleaning systems that flush out sediment deposits using the power of drainage flows. The research entailed field observations, laboratory experiments, and numerical simulations. The specific role of each of these investigative tools is summarized below: a) The field observations were aimed at understanding typical sedimentation patterns and their dependence on culvert geometry and hydrodynamic conditions during normal and extreme hydrologic events. b) The laboratory experiments were used for modeling sedimentation process observed insitu and for testing alternative self-cleaning concepts applied to culverts. The major tasks for the initial laboratory model study were to accurately replicate the culvert performance curves and the dynamics of sedimentation process, and to provide benchmark data for numerical simulation validation. c) The numerical simulations enhanced the understanding of the sedimentation processes and aided in testing flow cases complementary to those conducted in the model reducing the number of (more expensive) tests to be conducted in the laboratory. Using the findings acquired from the laboratory and simulation works, self-cleaning culvert concepts were developed and tested for a range of flow conditions. The screening of the alternative concepts was made through experimental studies in a 1:20 scale model guided by numerical simulations. To ensure the designs are effective, performance studies were finally conducted in a 1:20 hydraulic model using the most promising design alternatives to make sure that the proposed systems operate satisfactory under closer to natural scale conditions.

Computational and statistical analysis of copy number variants in normal and cancer genomes

AbstractAlthough the genomes from any two human individuals are more than 99.99% identical at the sequence level, some structural variation can be observed. Differences between genomes include single nucleotide polymorphism (SNP), inversion and copy number changes (gain or loss of DNA). The latter can range from submicroscopic events (CNVs, at least 1kb in size) to complete chromosomal aneuploidies. Small copy number variations have often no (lethal) consequences to the cell, but a few were associated to disease susceptibility and phenotypic variations. Larger re-arrangements (i.e. complete chromosome gain) are frequently associated with more severe consequences on health such as genomic disorders and cancer. High-throughput technologies like DNA microarrays enable the detection of CNVs in a genome-wide fashion. Since the initial catalogue of CNVs in the human genome in 2006, there has been tremendous interest in CNVs both in the context of population and medical genetics. Understanding CNV patterns within and between human populations is essential to elucidate their possible contribution to disease. But genome analysis is a challenging task; the technology evolves rapidly creating needs for novel, efficient and robust analytical tools which need to be compared with existing ones. Also, while the link between CNV and disease has been established, the relative CNV contribution is not fully understood and the predisposition to disease from CNVs of the general population has not been yet investigated.During my PhD thesis, I worked on several aspects related to CNVs. As l will report in chapter 3, ! was interested in computational methods to detect CNVs from the general population. I had access to the CoLaus dataset, a population-based study with more than 6,000 participants from the Lausanne area. All these individuals were analysed on SNP arrays and extensive clinical information were available. My work explored existing CNV detection methods and I developed a variety of metrics to compare their performance. Since these methods were not producing entirely satisfactory results, I implemented my own method which outperformed two existing methods. I also devised strategies to combine CNVs from different individuals into CNV regions.I was also interested in the clinical impact of CNVs in common disease (chapter 4). Through an international collaboration led by the Centre Hospitalier Universitaire Vaudois (CHUV) and the Imperial College London I was involved as a main data analyst in the investigation of a rare deletion at chromosome 16p11 detected in obese patients. Specifically, we compared 8,456 obese patients and 11,856 individuals from the general population and we found that the deletion was accounting for 0.7% of the morbid obesity cases and was absent in healthy non- obese controls. This highlights the importance of rare variants with strong impact and provides new insights in the design of clinical studies to identify the missing heritability in common disease.Furthermore, I was interested in the detection of somatic copy number alterations (SCNA) and their consequences in cancer (chapter 5). This project was a collaboration initiated by the Ludwig Institute for Cancer Research and involved other groups from the Swiss Institute of Bioinformatics, the CHUV and Universities of Lausanne and Geneva. The focus of my work was to identify genes with altered expression levels within somatic copy number alterations (SCNA) in seven metastatic melanoma ceil lines, using CGH and SNP arrays, RNA-seq, and karyotyping. Very few SCNA genes were shared by even two melanoma samples making it difficult to draw any conclusions at the individual gene level. To overcome this limitation, I used a network-guided analysis to determine whether any pathways, defined by amplified or deleted genes, were common among the samples. Six of the melanoma samples were potentially altered in four pathways and five samples harboured copy-number and expression changes in components of six pathways. In total, this approach identified 28 pathways. Validation with two external, large melanoma datasets confirmed all but three of the detected pathways and demonstrated the utility of network-guided approaches for both large and small datasets analysis.RésuméBien que le génome de deux individus soit similaire à plus de 99.99%, des différences de structure peuvent être observées. Ces différences incluent les polymorphismes simples de nucléotides, les inversions et les changements en nombre de copies (gain ou perte d'ADN). Ces derniers varient de petits événements dits sous-microscopiques (moins de 1kb en taille), appelés CNVs (copy number variants) jusqu'à des événements plus large pouvant affecter des chromosomes entiers. Les petites variations sont généralement sans conséquence pour la cellule, toutefois certaines ont été impliquées dans la prédisposition à certaines maladies, et à des variations phénotypiques dans la population générale. Les réarrangements plus grands (par exemple, une copie additionnelle d'un chromosome appelée communément trisomie) ont des répercutions plus grave pour la santé, comme par exemple dans certains syndromes génomiques et dans le cancer. Les technologies à haut-débit telle les puces à ADN permettent la détection de CNVs à l'échelle du génome humain. La cartographie en 2006 des CNV du génome humain, a suscité un fort intérêt en génétique des populations et en génétique médicale. La détection de différences au sein et entre plusieurs populations est un élément clef pour élucider la contribution possible des CNVs dans les maladies. Toutefois l'analyse du génome reste une tâche difficile, la technologie évolue très rapidement créant de nouveaux besoins pour le développement d'outils, l'amélioration des précédents, et la comparaison des différentes méthodes. De plus, si le lien entre CNV et maladie a été établit, leur contribution précise n'est pas encore comprise. De même que les études sur la prédisposition aux maladies par des CNVs détectés dans la population générale n'ont pas encore été réalisées.Pendant mon doctorat, je me suis concentré sur trois axes principaux ayant attrait aux CNV. Dans le chapitre 3, je détaille mes travaux sur les méthodes d'analyses des puces à ADN. J'ai eu accès aux données du projet CoLaus, une étude de la population de Lausanne. Dans cette étude, le génome de plus de 6000 individus a été analysé avec des puces SNP et de nombreuses informations cliniques ont été récoltées. Pendant mes travaux, j'ai utilisé et comparé plusieurs méthodes de détection des CNVs. Les résultats n'étant pas complètement satisfaisant, j'ai implémenté ma propre méthode qui donne de meilleures performances que deux des trois autres méthodes utilisées. Je me suis aussi intéressé aux stratégies pour combiner les CNVs de différents individus en régions.Je me suis aussi intéressé à l'impact clinique des CNVs dans le cas des maladies génétiques communes (chapitre 4). Ce projet fut possible grâce à une étroite collaboration avec le Centre Hospitalier Universitaire Vaudois (CHUV) et l'Impérial College à Londres. Dans ce projet, j'ai été l'un des analystes principaux et j'ai travaillé sur l'impact clinique d'une délétion rare du chromosome 16p11 présente chez des patients atteints d'obésité. Dans cette collaboration multidisciplinaire, nous avons comparés 8'456 patients atteint d'obésité et 11 '856 individus de la population générale. Nous avons trouvés que la délétion était impliquée dans 0.7% des cas d'obésité morbide et était absente chez les contrôles sains (non-atteint d'obésité). Notre étude illustre l'importance des CNVs rares qui peuvent avoir un impact clinique très important. De plus, ceci permet d'envisager une alternative aux études d'associations pour améliorer notre compréhension de l'étiologie des maladies génétiques communes.Egalement, j'ai travaillé sur la détection d'altérations somatiques en nombres de copies (SCNA) et de leurs conséquences pour le cancer (chapitre 5). Ce projet fut une collaboration initiée par l'Institut Ludwig de Recherche contre le Cancer et impliquant l'Institut Suisse de Bioinformatique, le CHUV et les Universités de Lausanne et Genève. Je me suis concentré sur l'identification de gènes affectés par des SCNAs et avec une sur- ou sous-expression dans des lignées cellulaires dérivées de mélanomes métastatiques. Les données utilisées ont été générées par des puces ADN (CGH et SNP) et du séquençage à haut débit du transcriptome. Mes recherches ont montrées que peu de gènes sont récurrents entre les mélanomes, ce qui rend difficile l'interprétation des résultats. Pour contourner ces limitations, j'ai utilisé une analyse de réseaux pour définir si des réseaux de signalisations enrichis en gènes amplifiés ou perdus, étaient communs aux différents échantillons. En fait, parmi les 28 réseaux détectés, quatre réseaux sont potentiellement dérégulés chez six mélanomes, et six réseaux supplémentaires sont affectés chez cinq mélanomes. La validation de ces résultats avec deux larges jeux de données publiques, a confirmée tous ces réseaux sauf trois. Ceci démontre l'utilité de cette approche pour l'analyse de petits et de larges jeux de données.Résumé grand publicL'avènement de la biologie moléculaire, en particulier ces dix dernières années, a révolutionné la recherche en génétique médicale. Grâce à la disponibilité du génome humain de référence dès 2001, de nouvelles technologies telles que les puces à ADN sont apparues et ont permis d'étudier le génome dans son ensemble avec une résolution dite sous-microscopique jusque-là impossible par les techniques traditionnelles de cytogénétique. Un des exemples les plus importants est l'étude des variations structurales du génome, en particulier l'étude du nombre de copies des gènes. Il était établi dès 1959 avec l'identification de la trisomie 21 par le professeur Jérôme Lejeune que le gain d'un chromosome supplémentaire était à l'origine de syndrome génétique avec des répercussions graves pour la santé du patient. Ces observations ont également été réalisées en oncologie sur les cellules cancéreuses qui accumulent fréquemment des aberrations en nombre de copies (telles que la perte ou le gain d'un ou plusieurs chromosomes). Dès 2004, plusieurs groupes de recherches ont répertorié des changements en nombre de copies dans des individus provenant de la population générale (c'est-à-dire sans symptômes cliniques visibles). En 2006, le Dr. Richard Redon a établi la première carte de variation en nombre de copies dans la population générale. Ces découvertes ont démontrées que les variations dans le génome était fréquentes et que la plupart d'entre elles étaient bénignes, c'est-à-dire sans conséquence clinique pour la santé de l'individu. Ceci a suscité un très grand intérêt pour comprendre les variations naturelles entre individus mais aussi pour mieux appréhender la prédisposition génétique à certaines maladies.Lors de ma thèse, j'ai développé de nouveaux outils informatiques pour l'analyse de puces à ADN dans le but de cartographier ces variations à l'échelle génomique. J'ai utilisé ces outils pour établir les variations dans la population suisse et je me suis consacré par la suite à l'étude de facteurs pouvant expliquer la prédisposition aux maladies telles que l'obésité. Cette étude en collaboration avec le Centre Hospitalier Universitaire Vaudois a permis l'identification d'une délétion sur le chromosome 16 expliquant 0.7% des cas d'obésité morbide. Cette étude a plusieurs répercussions. Tout d'abord elle permet d'effectuer le diagnostique chez les enfants à naître afin de déterminer leur prédisposition à l'obésité. Ensuite ce locus implique une vingtaine de gènes. Ceci permet de formuler de nouvelles hypothèses de travail et d'orienter la recherche afin d'améliorer notre compréhension de la maladie et l'espoir de découvrir un nouveau traitement Enfin notre étude fournit une alternative aux études d'association génétique qui n'ont eu jusqu'à présent qu'un succès mitigé.Dans la dernière partie de ma thèse, je me suis intéressé à l'analyse des aberrations en nombre de copies dans le cancer. Mon choix s'est porté sur l'étude de mélanomes, impliqués dans le cancer de la peau. Le mélanome est une tumeur très agressive, elle est responsable de 80% des décès des cancers de la peau et est souvent résistante aux traitements utilisés en oncologie (chimiothérapie, radiothérapie). Dans le cadre d'une collaboration entre l'Institut Ludwig de Recherche contre le Cancer, l'Institut Suisse de Bioinformatique, le CHUV et les universités de Lausanne et Genève, nous avons séquencés l'exome (les gènes) et le transcriptome (l'expression des gènes) de sept mélanomes métastatiques, effectués des analyses du nombre de copies par des puces à ADN et des caryotypes. Mes travaux ont permis le développement de nouvelles méthodes d'analyses adaptées au cancer, d'établir la liste des réseaux de signalisation cellulaire affectés de façon récurrente chez le mélanome et d'identifier deux cibles thérapeutiques potentielles jusqu'alors ignorées dans les cancers de la peau.

Parametrial adipose tissue and metabolic dysfunctions induced by fructose-rich diet in normal and neonatal-androgenized adult female rats.

Hyperandrogenemia predisposes an organism toward developing impaired insulin sensitivity. The aim of our study was to evaluate endocrine and metabolic effects during early allostasis induced by a fructose-rich diet (FRD) in normal (control; CT) and neonatal-androgenized (testosterone propionate; TP) female adult rats. CT and TP rats were fed either a normal diet (ND) or an FRD for 3 weeks immediately before the day of study, which was at age 100 days. Energy intake, body weight (BW), parametrial (PM) fat characteristics, and endocrine/metabolic biomarkers were then evaluated. Daily energy intake was similar in CT and TP rats regardless of the differences in diet. When compared with CT-ND rats, the TP-ND rats were heavier, had larger PM fat, and were characterized by basal hypoadiponectinemia and enhanced plasma levels of non-esterified fatty acid (NEFA), plasminogen activator inhibitor-1 (PAI-1), and leptin. FRD-fed CT rats, when compared with CT-ND rats, had high plasma levels of NEFA, triglyceride (TG), PAI-1, leptin, and adiponectin. The TP-FRD rats, when compared with TP-ND rats, displayed enhanced leptinemia and triglyceridemia, and were hyperinsulinemic, with glucose intolerance. The PM fat taken from TP rats displayed increase in the size of adipocytes, decrease in adiponectin (protein/gene), and a greater abundance of the leptin gene. PM adipocyte response to insulin was impaired in CT-FRD, TP-ND, and TP-FRD rats. A very short duration of isocaloric FRD intake in TP rats induced severe metabolic dysfunction at the reproductive age. Our study supports the hypothesis that the early-androgenized female rat phenotype is highly susceptible to developing endocrine/metabolic dysfunction. In turn, these abnormalities enhance the risk of metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorptionionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycinruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycinruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycinruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycinruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides.

Equilibrium curves and growth models to deal with forests in transition to uneven-aged structure : application in two sample stands

Abstract

Large differences in the prevalence of normal weight obesity using various cut-offs for excess body fat

BACKGROUND AND AIMS: Normal weight obesity (NWO) has been defined as an excessive body fat (BF) associated with a normal body mass index (BMI). Still, little is known regarding the effect of differing cut-offs for %BF on the prevalence of NWO. We thus conducted a study to assess the effect of modifying the cut-offs for excessive %BF on the prevalence of NWO. METHODS: We examined a convenience sample of 1523 Portuguese adults. BF was measured by validated hand-held bioimpedance. NWO was defined as a BMI < 25 kg/m2 and a %BF >30% or according to sex- and age-specific %BF cut-offs. RESULTS: Prevalence of NWO was 10.1% in women and 3.2% in men. In women, prevalence of NWO increased considerably with age, and virtually all women aged over 55 with a BMI < 25 kg/m2 were actually considered as NWO. Using sex-specific cut-offs for BF (men: 29.1%; women: 37.2%) led to moderately lower prevalence of NWO in women. Using sex and age-specific cut-offs for %BF considerably decreased the prevalence of NWO in women, i.e. 0.5e2.5% (depending on the criterion) but not in men, i.e. 1.9e3.4%. CONCLUSIONS: In women, the prevalence of NWO varies considerably according to the cut-off used to define excess BF, whereas a much smaller variation is found in men. While further studies are needed to describe the risk associated with NWO using various %BF cut-offs, this study suggests that sex- and age-specific cut-offs may be preferred.

Evaluation of Low-Cost Treatments on Rural Two-Lane Curves, TR-579, 2012

The objective of this project was to evaluate low-cost measures to reduce speeds on high-crash horizontal curves. The researchers evaluated two low-cost treatments in Iowa to determine their effectiveness in reducing speeds on rural two-lane roadways. This report summarizes how the research team selected sites and collected data, and the results. The team selected six sites. Retroreflective post treatments were added to existing chevrons at four sites and on-pavement curve markings were added at two sites. The researchers collected speed data before and after installation of the two treatments. The study compared several speed metrics to assess the effectiveness of the treatments. Overall, both were moderately effective in reducing speeds. The most significant impact of the treatments was in reducing the percentage of vehicles traveling over the posted or advisory speed by 5, 10, 15, or 20 or more mph. This result suggests that the treatments are most effective in reducing high-end speeds.

The normal distribution in some constrained sample spaces

Phenomena with a constrained sample space appear frequently in practice. This is the case e.g. with strictly positive data, or with compositional data, like percentages or proportions. If the natural measure of difference is not the absolute one, simple algebraic properties show that it is more convenient to work with a geometry different from the usual Euclidean geometry in real space, and with a measure different from the usual Lebesgue measure, leading to alternative models which better fit the phenomenon under study. The general approach is presented and illustrated using the normal distribution, both on the positive real line and on the D-part simplex. The original ideas of McAlister in his introduction to the lognormal distribution in 1879, are recovered and updated

Site quality curves for birch stands in north-western Spain

Abstract

hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

Colorectal cancers exhibit a high telomerase activity, usually correlated with the hypermethylation of the promoter of its hTERT catalytic subunit. Although telomerase is not expressed in normal tissue, certain proliferative somatic cells such as intestinal crypt cells have demonstrated telomerase activity. The aim of this study was to determine whether a correlation exists between telomerase activity, levels of hTERT methylation and telomere length in tumoral and normal colorectal tissues. Tumor, transitional and normal tissues were obtained from 11 patients with a colorectal cancer. After bisulfite modification of genomic DNA, hTERT promoter methylation was analyzed by methylation-sensitive single-strand conformation analysis (MS-SSCA). Telomerase activity and telomere length were measured by a fluorescent-telomeric repeat amplification protocol assay and by Southern blotting, respectively. A significant increase of hTERT methylation and telomerase activity, and a reduction of the mean telomere length were observed in the tumor tissues compared to the transitional and normal mucosa. In the transitional and normal mucosa, telomerase activity was significantly lower than that in tumor tissues, even with high levels of hTERT methylation. Nevertheless, hTERT promoter methylation was not linearly correlated to telomerase activity. These data indicate that hTERT promoter methylation is a necessary event for hTERT expression, as is telomerase activity. However, methylation is not sufficient for hTERT activation, particularly in normal colorectal cells.

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: Relevance to the diagnosis of neuroblastoma.

BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. CONCLUSIONS: A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. Pediatr Blood Cancer 2015;62:587-593. © 2015 Wiley Periodicals, Inc.

Smooth height/age curves from stem analysis with linear programming

[Abstract]

Résultats à deux ans de la trabéculoplastie sélective au laser dans le glaucome à angle ouvert et l'hypertonie oculaire

BACKGROUND: Selective laser trabeculoplasty (SLT) is a relatively new treatment strategy for the treatment of glaucoma. Its principle is similar to that of argon laser trabeculoplasty (ALT), but may lead to less damage to the trabecular meshwork. METHODS: We assessed the 2-year efficacy of SLT in a noncomparative consecutive case series. Any adult patient either suspected of having glaucoma or with open-angle glaucoma, whose treatment was judged insufficient to reach target intraocular pressure (IOP), could be recruited. IOP and number of glaucoma treatments were recorded over 2 years after the procedure. RESULTS: Our sample consisted of 44 consecutive eyes of 26 patients, aged 69+/-8 years. Eyes were treated initially on the lower 180 degrees . Three of them were retreated after 15 days on the upper 180. Fourteen eyes had ocular hypertension, 17 primary open-angle/normal-tension glaucoma, 11 pseudoexfoliation (PEX) glaucoma, and two pigmentary glaucoma. Thirty-six eyes had previously been treated and continued to be treated with topical anti-glaucoma medication, ten had had prior ALT, nine iridotomy, and 12 filtering surgery. The 2-year-follow up could not be completed for eight eyes because they needed filtering surgery. In the remaining 36 eyes, IOP decreased by a mean of 17.2%, 3.3 mmHg, (19.2+/-4.7 to 15+/-3.6 mmHg) after 2 years (p<0.001). As a secondary outcome, the number of glaucoma treatments decreased from 1.44 to 1.36 drops/patient. Other results according to subgroups of patients are analyzed: the greatest IOP decrease occurred in eyes that had never been treated with anti-glaucoma medication or with PEX glaucoma. SLT was probably valuable in a few eyes after filtering surgery; however, the statistical power of the study was not strong enough to draw a firm conclusion. When expressed in survival curves after 2 years, however, only 48% and 41% of eyes experienced a decrease of more than 3 mmHg or more than 20% of preoperative intraocular pressure, respectively. CONCLUSION: SLT decreases IOP somewhat for at least 2 years without an increase in topical glaucoma treatment. However, it cannot totally replace topical glaucoma treatment. In the future, patient selection should be improved to decrease the cost/effectiveness ratio.

Carbon-isotope stratigraphy and ammonite faunal turnover for the Middle Jurassic in the Southern Iberian palaeomargin

Variations in the stable carbon-isotope ratio of marine and continental sediments can reflect changes in sink and flux modifications of the palaeocarbon cycle. Here we report carbon-isotope compositions of Middle Jurassic marine carbonates from the Betic Cordillera (southern Spain), which represents an ideal region to link the stable carbon-isotope curves directly to ammonite zones and subzones, and thereby for the first time achieve an accurate chronostratigraphic calibration. The five sections studied represent basin and high swell deposits of the Southern Iberian palaeomargin. We find a similar delta C-13 of carbonates between different oceanic areas, suggesting a homogeneous carbon-isotope oceanic reservoir through the Middle Jurassic. The Aalenian-Bajocian transition is a critical period in ammonite evolution; hence the Early Jurassic fauna are replaced by new ammonite families which become dominant throughout the Middle and Late Jurassic. For this reason, we compared the delta C-13 values of carbonates with ammonite diversity and extinction rates at different taxonomical levels in order to explore the possible relationship between the carbon cycle and ammonite evolution. The carbon-isotope values of carbonates are not exactly linearly correlated with the extinction rate and ammonite diversity, but the main faunal turnovers follow minimum delta C-13 values, where extinct taxa are replaced by new ones. Likewise, radiation episodes are associated with increasing delta C-13 values and with transgressive sea-level rise. All these data support the idea that perturbations in the global carbon cycle reflect rapid palaeoenvironmental changes. We made detailed analyses of these faunal turnovers, using them as a proxy to identify major palaeoenvironmental crises in their ecosystems forced by modification in the carbon cycle. (c) 2006 Elsevier B.V All rights reserved.