Headline Annual Report 2010

Headline is Ireland's national media monitoring programme, working to promote responsible and accurate coverage of mental health and suicide related issues within the Irish media.Headline aims to highlight mental health issues and address the stigma attached to emotional distress, suicidal behaviour and mental illness through the promotion of responsible media coverage.

Headline Annual Report 2011

Headline is Ireland's national media monitoring programme, working to promote responsible and accurate coverage of mental health and suicide related issues within the Irish media.Headline aims to highlight mental health issues and address the stigma attached to emotional distress, suicidal behaviour and mental illness through the promotion of responsible media coverage.

Population pharmacokinetics of imatinib in CML and GIST patients under long-term treatment

Imatinib (Glivec®) has transformed the treatment and short-term prognosis of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST). However, the treatment must be taken indefinitely and 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), and is also bound to the alpha1-acid glycoprotein (AAG) in plasma. 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 individualisation. 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 were measured in 59 patients receiving Glivec® at diverse dosage regimens, using a validated chromatographic method developed for this study. The results were analysed by non-linear mixed effect modelling (NONMEM). A one-compartment model with first-order absorption described the data appropriately, with an average apparent clearance of 12.4 l/h, a volume of distribution 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. The MDR1 polymorphism 3435C>T and the AAG phenotype appears to modulate the disposition of imatinib. Large inter-individual variability (CV %) 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 programme for imatinib. It may help in individualising 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.

A three-year aeropalynological study in Estepona (southern Spain).

An aeropalynological study was carried out in the atmosphere of Estepona, a very popular tourist resort situated in the "Costa del Sol", (southern Spain) based on the data obtained during a three year air-monitoring programme (March 1995 to March 1998) using a volumetric pollen trap. The 34 taxa that reached a 10-day mean air pollen concentration equal to or greater than 1 grain of pollen/m(3) of air are reflected in the calendar. The first 10 taxa, in order of abundance, were: Cupressaceae, Olea europaea, Quercus, Poaceae, Urticaceae, Plantago, Pinus, Chenopodiaceae-Amaranthaceae, Ericaceae and Castanea, the first 3 of which accounted for approximately 56 % of the annual total pollen count. The greatest diversity of pollen type occurred during spring, while the highest pollen concentrations were reached from February-June, when approximately more than 80 % of the annual total pollen was registered. The lowest concentrations were obtaining during January, August and September. The annual quantity of pollen collected, the intensity and the dates on which the maximum peaks were recorded differed for the 3 years studied, which can be explained by reference to various meteorological parameters, especially rainfall and temperature. The pollen calendar spectrum is typically Mediterranean and similar to those of nearby localities, in which many pollen types are represented and the long tails indicating long flowering periods.

Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.

AIM: This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. METHODS: All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®). RESULTS: A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%), central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc . Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg(-1) , at extended intervals to achieve adequate concentrations. CONCLUSIONS: This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.

Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability

Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST). Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha(1)-acid glycoprotein. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Influence of KIT genotype was also assessed in GIST patients. Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7+/-0.6 for a two-fold free AUC increase in GIST; P<0.001). Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6+/-1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). In CML, no straightforward concentration-response relationships were obtained. Our findings represent additional arguments to further evaluate the usefulness of individualizing imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients.

Population pharmacokinetics of imatinib in CML and GIST patients under long-term treatment

Imatinib (Glivec®) has transformed the treatment and short-term prognosis of chronic myeloid leukaemia (CML) and gastro-intestinal stromal tumour (GIST). However, the treatment must be taken indefinitely, it is not devoid of inconvenience and toxicity. Moreover, resistance or escape from disease control occur 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 individualisation. 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 latest dose, were measured in 59 patients receiving Glivec® at diverse regimens, using a validated chromatographic method (HPLC-UV) developed for this study. The results were analysed by non-linear mixed effect modelling (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. The MDR1 polymorphism 3435C>T appears to affect the disposition 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 programme for imatinib. It may help to individualise 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.

Identificação da Rede de Monitorização da Quantidade de Agua da Bacia Hidrográfica da Ribeira Seca – Cabo Verde - Princípios e Monitorização

Cabo Verde é um País insular, situado à 500kms da costa Ocidental Africana. Composto por 10 ilhas de origem vulcânicas, pertencentes a zona climática Saheliana árida, onde a precipitação anual é muito limitada e a estação das chuvas vai de Agosto a Outubro. A área do estudo é a bacia hidrográfica de Ribeira Seca, situada na parte nordeste da ilha de Santiago. De acordo com o Censo 2000, a população da bacia é estimada em 14.343 habitantes. Apesar de ser uma das bacias mais exploradas de Santiago, do ponto de vista da extracção da água, não existe um único piezométro. A obtenção de valores do volume explorado na bacia é uma tarefa bastante difícil, uma vez que a grande maioria dos poços e nascentes não é licenciado. Um conjunto de pontos de observação, onde periodicamente se efectua as medições do nível da água e o caudal das nascentes, constitui a rede de quantidade de água que compreende a rede piezométrica e a de caudais das nascentes. Este trabalho pretende elaborar uma rede de referência de quantidade de água que visa essencialmente a caracterização do recurso e o acompanhamento da sua evolução espaço-temporal para uma adequada gestão do mesmo.

Talviaikainen happitilanne eräissä Pohjois-Savon järvissä vuosina 1997-2008

Pohjois-Savossa seurattiin talviaikaista happitilannetta vuosina 1997-2008. Seurannan kohteena oli neljä pienehköä järveä (Iso-Valkeinen, Kevätön, Kolmisoppi ja Vehmasjärvi), jotka ovat erityyppisiä syvyydeltään, rehevyystasoltaan ja humuspitoisuudeltaan. Näiden esimerkkijärvien oli tarkoitus antaa yleisemminkin viitteitä happitilanteen kehityksestä talven aikana. Alkutalven tulosten perusteella annettiin vuosittain tiedote, jossa arvioitiin happikatojen mahdollisuutta kevättalven kuluessa. Yleisöllä oli myös mahdollisuus seurata happi- ja lämpötilatuloksia Pohjois-Savon ympäristökeskuksen verkkopalvelun kautta. Hapenkulutusnopeus oli rehevimmässä seurantajärvessä kaksinkertainen verrattuna karumpiin ja syvyyden myötä ero vain korostui. Pohjanläheisessä vesikerroksessa 1 mg/l:n happipitoisuus kului karuissa järvissä noin kahdessa viikossa ja rehevässä noin kolmessa päivässä. Vuosien välinen vaihtelu oli kuitenkin hyvin suurta. Vaihtelu oli suurta myös karuissa järvissä. Veden jäätymisajankohdalla ja veden lämpötilalla on merkittävä vaikutus siihen, millainen kevättalven happitilanteesta muodostui. Seurantajärvien aineiston perusteella voidaan karkeasti arvioida, että kuukauden viivästyminen jäätymisessä tai vesipatsaan viilentyminen ennen jäätymistä asteen verran kylmemmäksi merkitsevät noin kolmanneksen korkeampaa happipitoisuutta kevättalvella. Vesipatsaan happitilanteen heikentymisen sekä ravinne- ja rautapitoisuuksien välillä todettiin vahvat yhteydet. Kaikkien järvien aineistossa happitilanteen heikkeneminen johti voimakkaimmin alusveden ammoniumtyppi-, kokonaisfosfori- ja rautapitoisuuksien kasvuun. Pitoisuusmuutokset olivat talven aikana suurimmat rehevimmässä kohdejärvessä, Kevättömässä, jossa kokonaisfosforipitoisuudet keskimäärin kymmenkertaistuivat, fosfaattifosforipitoisuudet kasvoivat keskimäärin 20-kertaisiksi ja rautapitoisuudet yli seitsenkertaisiksi.

Patoturvallisuusopas

Uusi patoturvallisuuslaki (494/2009) tuli voimaan 1.10.2009 ja valtioneuvoston asetus patoturvallisuudesta (319/2010) 5.5.2010. Tämä patoturvallisuusopas korvaa patoturvallisuusohjeet (MMM:n julkaisuja 7/1997), jotka poistuivat käytöstä 1.10.2009. Patoturvallisuusoppaassa esitetty ei ole padon omistajaa sitovaa, vaan oppaan tarkoitus on täydentää ja selventää esimerkein ja selostuksin laissa ja asetuksessa esitettyä. Oppaassa käsitellään padon suunnittelua kuten hydrologista mitoitusta ja padon teknisiä turvallisuusvaatimuksia, padon rakentamista ja käyttöönottoa sekä vahingonvaaraselvitystä, padon omistajan turvallisuussuunnitelmaa sekä padon kunnossapitoa, käyttöä, tarkkailua, vuosi- ja määräaikaistarkastuksia. Padot luokitellaan vahingonvaaran perusteella luokkiin 1, 2 ja 3. Luokittelua ei tarvitse kuitenkaan tehdä, jos patoturvallisuusviranomainen katsoo, että padosta ei aiheudu vaaraa. Jokaiselle luokitellulle padolle on padon omistajan laadittava tarkkailuohjelma, jonka patoturvallisuusviranomainen hyväksyy päätöksellään. Padosta aiheutuvan vahingonvaaran selvittämiseksi 1-luokan padon omistajan on laadittava vahingonvaaraselvitys padosta ihmisille, omaisuudelle ja ympäristölle aihetuvasta vahingonvaarasta. Myös muusta kuin 1-luokan padosta voi patoturvallisuusviranomainen määrätä tehtäväksi vahingonvaaraselvityksen luokittelua varten. Padon omistajan on laadittava 1-luokan padolle turvallisuussuunnitelma onnettomuus- ja häiriötilanteiden varalle. Suunnitelmassa esitetään padon omistajan omatoiminen varautuminen em. tilanteiden varalle. Pelastusviranomainen arvioi tapauskohtaisesti pelastuslain mukaisen suunnitelman laatimistarpeen. Padon omistajan on toimitettava patoturvallisuusviranomaiselle tietojärjestelmään vietäväksi patoturvallisuusasetuksessa mainitut tiedot. Patoturvallisuusviranomaisen ja padon omistajan on säilytettävä kustakin luokitellusta padosta ajantasaiset tulosteet tietojärjestelmästä sekä muut padon turvallisuuden kannalta tärkeät asiakirjat patoturvallisuuskansiossa siten, että ne ovat mahdollisissa häiriötilanteissa nopeasti saatavilla.

Dam safety guide

A new Dam Safety Act (494/2009) came into force on 1st October 2009 and a Government Decree on Dam Safety (319/2010) on 5th May 2010. This Dam Safety Guide replaces the Dam Safety Code of Practice (Publication of the Ministry of Agriculture and Forestry 7/1997), removed from circulation on 1st October 2009. The Dam Safety Guide is not binding on the dam owner; the purpose is to complement and elucidate the relevant law and and decree through examples and descriptions. The Guide takes up questions concerning dam design, for instance hydrological dimensioning and technical safety requirements, dam construction and use, the dam break hazard analysis and the dam owner’s emergency action plan, maintenance, use, monitoring as well as the annual and periodic inspections. Dams are classified according to the hazard they pose into class 1, 2 or 3 dams. The classification is not needed, if, according to the dam safety authority, the dam poses no danger. The owner of a classified dam must prepare a monitoring programme, to be approved by decision of the dam safety authority. To establish the hazard caused by a dam, the owner of a class 1 dam must prepare an analysis of the dam hazard to humans and property as well as to the environment. The dam safety authority may also require a dam break hazard analysis for a dam other than class 1 dam if deemed necessary for classification. The owner of a class 1 dam must prepare a plan of measures in case of emergency or operational failure. The plan shall present the dam owner’s state of preparedness to act on their own initiative in the situations described above. In each case, the rescue authorities make a separate assessment for the need to prepare a plan as set out in the Rescue Act. The dam owner must provide the information specified in the Dam Safety Decree to be entered into the dam safety information system. The dam safety authority and the owner of the dam must keep up-to-date printouts in their own dam safety files from the information system for each dam as well as other important documents connected with dam safety to ensure that these are readily available in case of disturbance.

Alcances y limitaciones del modelo de privatización del agua en Bolivia como política pública auspiciada desde organismos internacionales (Década 2000-2010)

Bajo la tipología de estudio de caso, la presente investigación pretende explicar la influencia ejercida desde el Banco Mundial en la configuración de políticas públicas nacionales en Bolivia para la privatización del suministro, transporte y acceso al agua potable. El objetivo general de la investigación es explicar los alcances y limitaciones del modelo de privatización del agua en Bolivia como política pública, promovido por el Banco Mundial (BM), en la primera década del siglo XXI. Sosteniendo que el modelo de privatización del BM ha sido permeado y superado por el interés nacional del pueblo boliviano en materia de acceso al agua. Finalmente, la metodología empleada será de corte cualitativa a partir del análisis de documentos oficiales, textos académicos y científicos, legislaciones y disposiciones tomadas desde el BM y desde Bolivia en lo que respecta a la privatización del agua.

Helminths of lizards from the municipality of Aripuanã in the southern Amazon region of Brazil

Ninety-five specimens from 13 species of lizard collected during a herpetofaunal monitoring programme of the Faxinal II power plant, municipality of Aripuanã, state of Mato Grosso, Brazil (southern Amazon region) were examined for helminths. A total of 21 helminth species (16 Nematoda, 1 Cestoda and 4 Trematoda) were recovered, with an overall prevalence of 67.37%. Seventeen new host records and seven new locality records are reported. A low number of specialists and core helminth species were found. Lizard body size was positively correlated with both the total number of helminth species and individuals. Active foragers exhibited higher helminth diversity. However, sit-and-wait foragers, especially Plica plica, had similar diversity values as active foragers and harboured more helminth species. The degree of similarity in helminth fauna was higher among closely related host species. Copyright © 2011 Cambridge University Press.

A qualitative risk assessment approach for Swiss dairy products: opportunities and limitations

Switzerland implemented a risk-based monitoring of Swiss dairy products in 2002 based on a risk assessment (RA) that considered the probability of exceeding a microbiological limit value set by law. A new RA was launched in 2007 to review and further develop the previous assessment, and to make recommendations for future risk-based monitoring according to current risks. The resulting qualitative RA was designed to ascertain the risk to human health from the consumption of Swiss dairy products. The products and microbial hazards to be considered in the RA were determined based on a risk profile. The hazards included Campylobacter spp., Listeria monocytogenes, Salmonella spp., Shiga toxin-producing Escherichia coli, coagulase-positive staphylococci and Staphylococcus aureus enterotoxin. The release assessment considered the prevalence of the hazards in bulk milk samples, the influence of the process parameters on the microorganisms, and the influence of the type of dairy. The exposure assessment was linked to the production volume. An overall probability was estimated combining the probabilities of release and exposure for each combination of hazard, dairy product and type of dairy. This overall probability represents the likelihood of a product from a certain type of dairy exceeding the microbiological limit value and being passed on to the consumer. The consequences could not be fully assessed due to lack of detailed information on the number of disease cases caused by the consumption of dairy products. The results were expressed as a ranking of overall probabilities. Finally, recommendations for the design of the risk-based monitoring programme and for filling the identified data gaps were given. The aims of this work were (i) to present the qualitative RA approach for Swiss dairy products, which could be adapted to other settings and (ii) to discuss the opportunities and limitations of the qualitative method.

Antimicrobial resistance in bacteria from Swiss veal calves at slaughter

Bacteria with antimicrobial resistance can be transferred from animals to humans and may compromise antimicrobial treatment in case of infection. To determine the antimicrobial resistance situation in bacteria from Swiss veal calves, faecal samples from 500 randomly selected calves originating from 129 farms were collected at four big slaughterhouses. Samples were cultured for Escherichia coli, Enterococcus sp. and Campylobacter sp. and isolated strains were tested for antimicrobial susceptibility to selected antimicrobial agents by the minimal inhibitory concentration technique using the broth microdilution method. From 100 farms, data on farm management, animal husbandry and antimicrobial treatments of the calves were collected by questionnaire. Risk factors associated with antimicrobial resistance were identified by logistic regression. In total, 467 E. coli, 413 Enterococcus sp. and 202 Campylobacter sp. were isolated. Of those, 68.7%, 98.7% and 67.8%, respectively, were resistant to at least one of the tested antimicrobial agents. Resistance was mainly observed to antimicrobials frequently used in farm animals. Prevalence of resistance to antimicrobials important for human treatment was generally low. However, a rather high number of quinupristin/dalfopristin-resistant Enterococcus faecium and ciprofloxacin-resistant Campylobacter sp. were detected. External calf purchase, large finishing groups, feeding of milk by-products and administration of antimicrobials through feed upon arrival of the animals on the farm significantly increased the risk of antimicrobial resistance at farm level. Participation in a quality assurance programme and injection of a macrolide upon arrival of the animals on the farm had a protective effect. The present study showed that veal calves may serve as a reservoir for resistant bacteria. To ensure food safety, veal calves should be included in the national monitoring programme for antimicrobial resistance in farm animals. By improving farm management and calf husbandry the prevalence of resistance may be reduced.