A synoptic list of the fishes known to occur within fifty miles of Chicago, by S. E. Meek and S. F. Hildebrand.

Fieldiana Zoology v.7, no. 9

Relationships between imatinib plasma levels and efficacy

Purpose: While imatinib has revolutionized the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST), its pharmacokinetic-pharmacodynamic relationships have been poorly studied. This study aimed to explore the issue in oncologic patients, and to evaluate the specific influence of the target genotype in a GIST subpopulation. Patients and methods: Data from 59 patients (321 plasma samples) were collected during a previous pharmacokinetic study. Based on a population model purposely developed, individual post-hoc Bayesian estimates of pharmacokinetic parameters were derived, and used to estimate drug exposure (AUC; area under curve). Free fraction parameters were deduced from a model incorporating plasma alpha1-acid glycoprotein levels. Associations between AUC (or clearance) and therapeutic response (coded on a 3-point scale), or tolerability (4-point scale), were explored by ordered logistic regression. Influence of KIT genotype on response was also assessed in GIST patients. Results: Total and free drug exposure correlated with the number of side effects (p < 0.005). A relationship with response was not evident in the whole patient set (with good-responders tending to receive lower doses and bad-responders higher doses). In GIST patients however, higher free drug exposure predicted better responses. A strong association was notably observed in patients harboring an exon 9 mutation or a wild type KIT, known to decrease tumor sensitivity towards imatinib (p < 0.005). Conclusions: Our results are arguments to further evaluate the potential benefit of a therapeutic monitoring program for imatinib. Our data also suggest that stratification by genotype will be important in future trials.

Estudi d'impacte acústic de les obres d'un intercanviador de metro

En el territori del Barcelonès les obres han estat a l’ordre del dia. Abans de l’inici de la crisi es van encetar i programar nombroses obres tan d’immobles com de grans infraestructures com la que aquí es presenta: un intercanviador de metro. L’alta densitat demogràfica d’aquesta regió ha fet que aquests treballs realitzats a les obres siguin poc compatibles amb el benestar i la salut de la població. Un dels principals factors causants del malestar als veïns és el soroll. Mitjançant estudis de modelització acústica, com el realitzat en aquest projecte, es pretén preveure i evitar que l’afecció acústica derivada de les obres sigui perjudicial per la persona per tal de compatibilitzar al màxim possible les feines de l’obra amb el benestar general. Mitjançant el programa de monitorització acústica Cadna‐A i nombroses mesures acústiques in situ s’ha pogut preveure la futura afecció sonora de 6 fases d’obra considerades com les més sorolloses i s’han proposat un seguit de mesures preventives i/o correctores per tal d’assolir uns nivells acústics assequibles amb la legislació vigent.

Estudio del ecosistema urbano de San José. Protocolo de monitoreo de aves y naturalización del Parque La Sabana

El papel de la ciudad en el futuro de la humanidad será transcendente, y es que el crecimiento actual de los espacios urbanos tiende, en general, a desbordar el sitio original de las ciudades, abarcando territorios cada vez más extensos y discontinuos. Y por este motivo es de vital importancia el estudio de la ciudad y de su entorno, el cual es sinónimo de ecosistema urbano. En el siguiente estudio se evalúa el ecosistema urbano de San José, capital de Costa Rica, dando énfasis en las zonas verdes presentes, en las relaciones con los ecosistemas naturales circundantes y como mejorar su capacidad ecológica. Por este motivo se ha analizado un proceso de rearborización en el Parque Metropolitano La Sabana, principal nódulo de carga de la trama urbana. Este esfuerzo de naturación dotará al parque de una mayor naturalización, con lo que se espera un aumento de la biodiversidad faunística. Para conocer estos cambios se crea un programa de monitoreo de aves con su respectivo protocolo.

Resistance of Aedes aegypti from the state of São Paulo, Brazil, to organophosphates insecticides

Since the reintroduction of Aedes aegypti in the state of São Paulo, in the middle of the 1980-decade, organophosphate insecticides are being used to control the dengue vector. In 1996, an annual program for monitoring the susceptibility of Ae. aegypti to the insecticides was implemented. Some of the results of this monitoring program are presented. Ae. aegypti populations from ten localities have been submitted to bioassays with the diagnostic dose of temephos and fenitrothion. Only two (Marília and Presidente Prudente) remain susceptible to both insecticides and one (Santos) exhibits true resistance. Ae. aegypti from the remaining localities showed an incipient altered susceptibility. Resistance ratios varied from 1.2 to 2.9 for temephos and from 1.5 to 3.2 to fenitrothion, indicating moderate levels of resistance. Biochemical assays did not detect alterations in the enzyme acetilcholinesterase, but indicated that resistance is associated with esterases.

Aedes aegypti resistance to temephos during 2001 in several municipalities in the states of Rio de Janeiro, Sergipe, and Alagoas, Brazil

For more than 30 years temephos, an organophosphate insecticide, has been the sole larvicide used in Brazil in the control of Aedes aegypti. Organophosphates were also used for adult control, being replaced by pyrethroids since l999. In this same year, the Brazilian Health Foundation started the coordination of the Ae. aegypti Insecticide Resistance Monitoring Program. In the context of this program, our group was responsible for the detection of temephos resistance in a total of 12 municipalities in the states of Rio de Janeiro (RJ), Alagoas (AL), and Sergipe (SE) during 2001. In each municipality, a pool of mosquitoes collected from different districts was used, with the exception of Rio de Janeiro city, where eight districts have been separately evaluated. Exposure of larvae to the diagnostic dose of temephos revealed resistance in all localities examined, with mortality levels ranging from 4% (Pilares district, Rio de Janeiro, RJ) to 61.9% (Campos dos Goytacazes, RJ). Quantification of mortality showed resistance ratios from 6.1 (Aracaju, SE) to 16.8 (São Gonçalo, RJ and Penha district, Rio de Janeiro, RJ). The national dengue control program is presently using these data to subside insecticide resistance management.

Population pharmacokinetic study of gentamicin: A retrospective analysis in a large cohort of neonate patients

Objectives: Gentamicin is one of the most commonly prescribed antibiotics for suspected or proven infection in newborns. Because of age-associated (pre- and post- natal) changes in body composition and organ function, large interindividual variability in gentamicin drug levels exists, thus requiring a close monitoring of this drug due to its narrow therapeutic index. We aimed to investigate clinical and demographic factors influencing gentamicin pharmacokinetics (PK) in a large cohort of unselected newborns and to explore optimal regimen based on simulation. Methods: All gentamicin concentration data from newborns treated at the University Hospital Center of Lausanne between December 2006 and October 2011 were retrieved. Gentamicin concentrations were measured within the frame of a routine therapeutic drug monitoring program, in which 2 concentrations (at 1h and 12h) are systematically collected after the first administered dose, and a few additional concentrations are sampled along the treatment course. A population PK analysis was performed by comparing various structural models, and the effect of clinical and demographic factors on gentamicin disposition was explored using NONMEM®. Results: A total of 3039 concentrations collected in 994 preterm (median gestational age 32.3 weeks, range 24.2-36.5 weeks) and 455 term newborns were used in the analysis. Most of the data (86%) were sampled after the first dose (C1 h and C12 h). A two-compartment model best characterized gentamicin PK. Average clearance (CL) was 0.044 L/h/kg (CV 25%), central volume of distribution (Vc) 0.442 L/kg (CV 18%), intercompartmental clearance (Q) 0.040 L/h/kg and peripheral volume of distribution (Vp) 0.122 L/kg. Body weight, gestational age and postnatal age positively influenced CL. The use of both gestational age and postnatal age better predicted CL than postmenstrual age alone. CL was affected by dopamine and furosemide administration and non-significantly by indometacin. Body weight, gestational age and dopamine coadminstration significantly influenced Vc. Model based simulation confirms that preterm infants need higher dose, superior to 4 mg/kg, and extended interval dosage regimen to achieve adequate concentration. Conclusions: This study, performed on a very large cohort of neonates, identified important factors influencing gentamicin PK. The model will serve to elaborate a Bayesian tool for dosage individualization based on a single measurement.

Imatinib plasma concentrations variability in oncologic patients

Imatinib (Glivec®) has transformed the treatment and short-term prognosis of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, the treatment must be taken indefinitely, it is not devoid of inconvenience and toxicity. Moreover, resistance or escape from disease control occurs in a significant number of patients. Imatinib is a substrate of the cytochromes P450 CYP3A4/5 and of the multidrug transporter P-glycoprotein (product of the MDR1 gene). Considering the large inter-individual differences in the expression and function of those systems, the disposition and clinical activity of imatinib can be expected to vary widely among patients, calling for dosage individualization. The aim of this exploratory study was to determine the average pharmacokinetic parameters characterizing the disposition of imatinib in the target population, to assess their inter-individual variability, and to identify influential factors affecting them. A total of 321 plasma concentrations, taken at various sampling times after the latest dose, were measured in 59 patients receiving Glivec at diverse regimens, using a validated HPLC-UV method developed for this study. The results were analyzed by non-linear mixed effect modeling (NONMEM). A one-compartment model with first-order absorption appeared appropriate to describe the data, with an average apparent clearance of 12.4 l/h, a distribution volume of 268 l and an absorption constant of 0.47 h-1. The clearance was affected by body weight, age and sex. No influences of interacting drugs were found. DNA samples were used for pharmacogenetic explorations. At present, only the MDR1 polymorphism has been assessed and seems to affect the pharmacokinetic parameters of imatinib. Large inter-individual variability remained unexplained by the demographic covariates considered, both on clearance (40 %) and distribution volume (71 %). Together with intra-patient variability (34 %), this translates into an 8-fold width of the 90 %-prediction interval of plasma concentrations expected under a fixed dosing regimen. This is a strong argument to further investigate the possible usefulness of a therapeutic drug monitoring program for imatinib. It may help to individualize the dosing regimen before overt disease progression or observation of treatment toxicity, thus improving both the long-term therapeutic effectiveness and tolerability of this drug.

Imatinib plasma concentrations variability in oncologic patients

The anticancer drug imatinib has transformed the treatment and prognosis of chronic myeloid leukemia and gastrointestinal stromal tumor. However, the treatment must be taken indefinitely and is not devoid of inconveniences and toxicity. Moreover, resistance or escape from disease control are occurring. Considering the large interindividual differences in the function of the enzymatic and transport systems involved in imatinib disposition, exposure to this drug can be expected to vary widely among patients. This book describes an observational clinical trial aiming at exploring the influence of these covariates on imatinib pharmacokinetics and assessing the interindividual variability of the pharmacokinetic parameters of the drug. A large interindividual variability was observed, together with some preliminary concentration-effect relationships. These elements are arguments to further investigate the potential benefit of a therapeutic drug monitoring program to optimize the use of imatinib in patients. Such results should be especially useful to clinical oncologists or scientists involved in clinical oncology research.

Developing methodologies to allow the robust prediction dynamic context dominated by perturbations

El principal objectiu del projecte era desenvolupar millores conceptuals i metodològiques que permetessin una millor predicció dels canvis en la distribució de les espècies (a una escala de paisatge) derivats de canvis ambientals en un context dominat per pertorbacions. En un primer estudi, vàrem comparar l'eficàcia de diferents models dinàmics per a predir la distribució de l'hortolà (Emberiza hortulana). Els nostres resultats indiquen que un model híbrid que combini canvis en la qualitat de l'hàbitat, derivats de canvis en el paisatge, amb un model poblacional espacialment explícit és una aproximació adequada per abordar canvis en la distribució d'espècies en contextos de dinàmica ambiental elevada i una capacitat de dispersió limitada de l'espècie objectiu. En un segon estudi abordarem la calibració mitjançant dades de seguiment de models de distribució dinàmics per a 12 espècies amb preferència per hàbitats oberts. Entre les conclusions extretes destaquem: (1) la necessitat de que les dades de seguiment abarquin aquelles àrees on es produeixen els canvis de qualitat; (2) el biaix que es produeix en la estimació dels paràmetres del model d'ocupació quan la hipòtesi de canvi de paisatge o el model de qualitat d'hàbitat són incorrectes. En el darrer treball estudiarem el possible impacte en 67 espècies d’ocells de diferents règims d’incendis, definits a partir de combinacions de nivells de canvi climàtic (portant a un augment esperat de la mida i freqüència d’incendis forestals), i eficiència d’extinció per part dels bombers. Segons els resultats dels nostres models, la combinació de factors antropogènics del regim d’incendis, tals com l’abandonament rural i l’extinció, poden ser més determinants per als canvis de distribució que els efectes derivats del canvi climàtic. Els productes generats inclouen tres publicacions científiques, una pàgina web amb resultats del projecte i una llibreria per a l'entorn estadístic R.

Iowa STORET Data Retrieval, 2002

Part of Iowa's Water Ambient monitoring Program, produced by the Iowa Department of Natural Resources.

Water Quality Summary, 2001

Part of Iowa's Water Ambient monitoring Program, produced by the Iowa Department of Natural Resources.

Big Spring Retrospective, March 2002

Part of Iowa's Water Ambient monitoring Program, produced by the Iowa Department of Natural Resources.

Year Two Accomplishments, 2002

Part of Iowa's Water Ambient monitoring Program, produced by the Iowa Department of Natural Resources.

Year One Accomplishments, 2002

Part of Iowa's Water Ambient monitoring Program, produced by the Iowa Department of Natural Resources.