Search

Changes in savanna tree species composition, both within landscapes and across climatic gradients, suggest that species differ in their ability to utilise resources and cope with grass competition. Linking trait variation among species to their relative performance under resource limitation and competition treatments could provide mechanistic understanding of species’ turnover across environmental gradients in savannas. We investigated how tree species differ in response to competition from grasses and nutrient supply, and whether these responses can be related to plant traits. As humid savannas are often associated with low fertility, species of humid savannas may grow more efficiently under nutrient suppression than species from semi-arid savannas. In heterogeneous grass swards, fast-growing, resource-wasteful species may be found in short-grass patches and slow-growing, resource-conservative species in tall-grass patches. 2. We compared seedlings of 40 tree species sampled from humid and semi-arid savannas of three continents (Africa, Australia, South America) with and without grass competition and with high and low nutrient supply. We measured traits related to soil resource capture, light capture and growth, and tested whether these traits were related to performance under the four treatments. 3. All tree species were suppressed by grass competition and most by nutrient limitation. Only species from humid savannas in Australia grew better under nutrient limitation than their semi-arid counterparts. Deciduous species from semi-arid climates were more negatively impacted by grass competition than deciduous species from humid climates whereas the reverse pattern was observed among evergreen species. Faster growing species were more severely suppressed by grass competition and low nutrients than slower growing species. Traits associated with soil resource capture and seed mass supported growth under grass competition and nutrient limitation, but the traits differed

Acute liver failure is idiopathic and drug-related in, respectively, around 50 and 15 % of children. Population-based, epidemiologic data about the pattern of disease manifestation and incidence of less severe acute liver injury, either idiopathic or potentially drug-attributed are limited in children and adolescents. (i) To assess the incidence of idiopathic acute liver injury (ALI) and its clinical features in children and adolescent outpatients; and (ii) to investigate the role of the drug as a potential cause of ALI which is considered idiopathic. A retrospective cohort study was performed during the years 2000-2008. Data were retrieved from three longitudinal electronic healthcare databases in two European countries: Pedianet and Health Search/CSD Longitudinal Patient Database from Italy and the Integrated Primary Care Information database from The Netherlands. Cases of idiopathic acute liver injury in population aged < 18 years were identified by exclusion of all competing causes of liver injury (e.g. viral, autoimmune hepatitis), according to CIOMS criteria. The potential role of drug exposure as actual underlying cause of idiopathic ALI was detected through signal detection mining techniques. Both pooled and country-specific incidence rates [IR/100,000 person-years (PYs)] of idiopathic ALI and pooled adjusted rate ratios (RR) of drugs identified as a potential cause of idiopathic ALI, plus 95 % confidence intervals (CI) were estimated using the custom-built software Jerboa. Among 785 definite cases of idiopathic ALI, the pooled IR was 62.4/100,000 PYs (95 % CI 58.1-66.8). The country-specific IR was higher in Italy (73.0/100,000 PYs, 95 % CI 67.8-78.4) than in The Netherlands (21.0/100,000 PYs, 95 % CI 16.0-27.2) and increased with age in both countries. Isolated elevations of liver enzymes were reported in around two-thirds of cases in Italy, while in The Netherlands the cases were more often identified by a combination of signs/symptoms. Among drugs detect

Background Gastroprotective strategies are recommended for nonsteroidal anti-inflammatory drug (NSAID) users at risk of upper gastrointestinal (UGI) complications. Aim To compare the use of gastroprotective strategies in NSAID users in three countries, and the subsequent impact of rofecoxib withdrawal. Methods We conducted a population-based cohort study in three general practice (GP) databases: (i) United Kingdom's (UK) GP Research Database (19982008); (ii) Italy's (IT) Health Search/CSD Longitudinal Patient Database (20002007); and (iii) the Dutch (NL) Integrated Primary Care Information database (19962006). Study cohorts comprised incident NSAID users =50 years. Preventive strategies included: (i) co-prescription of gastroprotective agents; or (ii) cyclooxygenase-2-selective inhibitor use. Under-use was defined as no gastroprotection in patients with =1 UGI risk factor (history of UGI event, age =65 years, concomitant use of anticoagulants, antiplatelets or glucocorticoids). Interrupted time-series analysis was performed to assess the impact of rofecoxib withdrawal on preventive strategies. Results The study populations consisted of 384 649 UK, 177 747 IT and 55 004 NL NSAID users. In UK, under-use of preventive strategies fell from 91% to 71% [linear trend (lt) P = 0.001], in NL from 92% to 58% (lt P < 0.001) and in IT from 90% to 76% (lt P = 0.38) in high-risk NSAID users. In 2000 and 2006, under-use was significantly lower in NL compared with UK and IT (P < 0.001) in high-risk users. After rofecoxib's withdrawal, under-use increased significantly in UK and NL. Conclusions The prescription of gastropreventive strategies followed a similar pattern across countries. Despite a temporary negative effect of rofecoxib withdrawal on under-use, improvement of gastroprotection with nonsteroidal anti-inflammatory drugs was observed.

Background: Traditional pharmacovigilance activities do not focus specifically on children and medicines in children are frequently prescribed off-label based on extrapolating experience from adults.[1] The EU-ADR Project aims to use information from various electronic healthcare record (EHR) databases to produce a computerised integrated system for early detection of drug safety signals.[2] Objectives: To provide estimates of the number of drugs and incidence rates (IRs) of adverse events that can be monitored in children and adolescents in the EU-ADR network. Methods: Demographic, clinical events and outpatient drug prescription/dispensing data were obtained for individuals 0 to 18 years of age from seven databases from Denmark, Italy, and the Netherlands. Data were analysed from 1996–2008. We estimated the number and types of drugs for which specific adverse events can be monitored as function of actual drug use, minimally detectable RR, and empiricallyderived incidence rates for 10 events deemed to be important in pharmacovigilance.[3,4] The same was done for adverse events frequently reported in children, using IRs described in literature. Results: The paediatric population comprised 4 838 146 individuals contributing 25 575 132 person-years (PYs) of follow-up during the study period. Within this population a total of 2170 drugs were prescribed, with a total drug exposure of 1 610 631 PYs. Eighteen of the 2170 drugs (0.8%) comprised half of total drug exposure while 90% of the total drug exposure in PYs was represented by 158 drugs (7.3%). For a relatively frequent event such as upper gastrointestinal bleeding (IR = 14.4/100 000 PYs), there were 39 drugs (comprising 66% of total exposure in PY) for which an association with a RR ‡4, if present, can be investigated. For a rare event such as anaphylactic shock, there were 8 drugs (comprising 35% of total exposure) for which an association of same magnitude can be investigated. Based on literature-derived IR, ther

Aim Electronic healthcare record (EHR)-based surveillance systems are increasingly being developed to support early detection of safety signals. It is unknown what the power of such a system is for surveillance among children and adolescents. In this paper we provide estimates of the number and classes of drugs, and incidence rates (IRs) of events, that can be monitored in children and adolescents (0-18 years). Methods Data were obtained from seven population-based EHR databases in Denmark, Italy, and the Netherlands during the period 1996-2010. We estimated the number of drugs for which specific adverse events can be monitored as a function of actual drug use, minimally detectable relative risk (RR) and IRs for 10 events. Results The population comprised 4 838 146 individuals (25 575 132 person years (PYs)), who were prescribed 2170 drugs (1 610 631 PYs drug-exposure). Half of the total drug-exposure in PYs was covered by only 18 drugs (0.8%). For a relatively frequent event like upper gastrointestinal bleeding there were 39 drugs for which an association with a RR ≥4, if present, could be investigated. The corresponding number of drugs was eight for a rare event like anaphylactic shock. Conclusion Drug use in children is rare and shows little variation. The number of drugs with enough exposure to detect rare adverse events in children and adolescents within an EHR-based surveillance system such as EU-ADR is limited. Use of additional sources of paediatric drug exposure information and global collaboration are imperative in order to optimize EHR data for paediatric safety surveillance.

Background Data mining in spontaneous reporting databases has shown that drug-induced liver injury is infrequently reported in children. Objectives Our objectives were to (i) identify drugs potentially associated with acute liver injury (ALI) in children and adolescents using electronic healthcare record (EHR) data; and (ii) to evaluate the significance and novelty of these associations. Methods We identified potential cases of ALI during exposure to any prescribed/dispensed drug for individuals <18 years old from the EU-ADR network, which includes seven databases from three countries, covering the years 1996-2010. Several new methods for signal detection were applied to identify all statistically significant associations between drugs and ALI. A drug was considered statistically significantly associated with ALI, using all other time as a reference category, if the 95 % CI lower band of the relative risk was >1 and in the presence of at least three exposed cases of ALI. Potentially new signals were distinguished from already known associations concerning ALI (whether in adults and/or in the paediatric population) through manual review of published literature and drug product labels. Results The study population comprised 4,838,146 individuals aged <18 years, who contributed an overall 25,575,132 person-years of follow-up. Within this population, we identified 1,015 potential cases of ALI. Overall, 20 positive drug-ALI associations were detected. The associations between ALI and domperidone, flunisolide and human insulin were considered as potentially new signals. Citalopram and cetirizine have been previously described as hepatotoxic in adults but not in children, while all remaining associations were already known in both adults and children. Conclusions Data mining of multiple EHR databases for signal detection confirmed known associations between ALI and several drugs, and identified some potentially new signals in children that require further investig

Changes in land use may lead to increased soil nutrient levels in many ecosystems (e.g. due to intensification of agricultural fertilizer use). Plant species differ widely in their response to differences in soil nutrients, and for savannas it is uncertain how this nutrient enrichment will affect plant community dynamics. We set up a large controlled short-term experiment in a semi-arid savanna to test how water supply (even water supply vs. natural rainfall) and nutrient availability (no fertilisation vs. fertilisation) affects seedlings’ above-ground biomass production and leaf-nutrient concentrations (N, P and K) of broadleafed and fine-leafed tree species. Contrary to expectations, neither changes in water supply nor changes in soil nutrient level affected biomass production of the studied species. By contrast, leaf-nutrient concentration did change significantly. Under regular water supply, soil nutrient addition increased the leaf phosphorus concentration of both fine-leafed and broad-leafed species. However, under uneven water supply, leaf nitrogen and phosphorus concentration declined with soil nutrient supply, this effect being more accentuated in broad-leafed species. Leaf potassium concentration of broad-leafed species was lower when growing under constant water supply, especially when no NPK fertilizer was applied. We found that changes in environmental factors can affect leaf quality, indicating a potential interactive effect between land-use changes and environmental changes on savanna vegetation: under more uneven rainfall patterns within the growing season, leaf quality of tree seedlings for a number of species can change as a response to changes in nutrient levels, even if overall plant biomass does not change. Such changes might affect herbivore pressure on trees and thus savanna plant community dynamics. Although longer term experiments would be essential to test such potential effects of eutrophication via changes in leaf nutrient concentration

PURPOSE: Neuroblastoma is a genetically heterogeneous pediatric tumor with a remarkably variable clinical behavior ranging from widely disseminated disease to spontaneous regression. In this study, we aimed for comprehensive genetic subgroup discovery and assessment of independent prognostic markers based on genome-wide aberrations detected by comparative genomic hybridization (CGH). MATERIALS AND METHODS: Published CGH data from 231 primary untreated neuroblastomas were converted to a digitized format suitable for global data mining, subgroup discovery, and multivariate survival analyses. RESULTS: In contrast to previous reports, which included only a few genetic parameters, we present here for the first time a strategy that allows unbiased evaluation of all genetic imbalances detected by CGH. The presented approach firmly established the existence of three different clinicogenetic subgroups and indicated that chromosome 17 status and tumor stage were the only independent significant predictors for patient outcome. Important new findings were: (1) a normal chromosome 17 status as a delineator of a subgroup of presumed favorable-stage tumors with highly increased risk; (2) the recognition of a survivor signature conferring 100% 5-year survival for stage 1, 2, and 4S tumors presenting with whole chromosome 17 gain; and (3) the identification of 3p deletion as a hallmark of older age at diagnosis. CONCLUSION: We propose a new regression model for improved patient outcome prediction, incorporating tumor stage, chromosome 17, and amplification/deletion status. These findings may prove highly valuable with respect to more reliable risk assessment, evaluation of clinical results, and optimization of current treatment protocols.