Overview CGMS and related tools

The main purpose of Crop Growth Monitoring System CGMS is to estimate the influence of weather conditions on crop growth and yield on regional scale (provinces, countries, continents). Therefore, CGMS combines aspects of both weather data processing and collection as well as modelling crop growth and development

Candidate biomarkers for treatment benefit from sunitinib in patients with advanced renal cell carcinoma using mass spectrometry-based (phospho)proteomics

The tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p-)proteomics will identify predictive biomarkers for treatment outcome of sunitinib, tumor tissues of 26 RCC patients were analyzed. Eight patients had primary resistant (RES) and 18 sensitive (SENS) RCC. A 78 phosphosite signature (p &lt; 0.05, fold-change &gt; 2) was identified; 22 p-sites were upregulated in RES (unique in RES: BCAR3, NOP58, EIF4A2, GDI1) and 56 in SENS (35 unique). EIF4A1/EIF4A2 were differentially expressed in RES at the (p-)proteome and, in an independent cohort, transcriptome level. Inferred kinase activity of MAPK3 (p = 0.026) and EGFR (p = 0.045) as determined by INKA was higher in SENS. Posttranslational modifications signature enrichment analysis showed that different p-site-centric signatures were enriched (p &lt; 0.05), of which FGF1 and prolactin pathways in RES and, in SENS, vanadate and thrombin treatment pathways, were most significant. In conclusion, the RCC (phospho)proteome revealed differential p-sites and kinase activities associated with sunitinib resistance and sensitivity. Independent validation is warranted to develop an assay for upfront identification of patients who are intrinsically resistant to sunitinib.</p

Agricultural biomass as provisioning ecosystem service: quantification of energy flows

Agro-ecosystems supply provisioning, regulating and cultural services to human society. This study focuses on the agro-ecosystem provisioning services regarding the production of agricultural biomass. These services strongly respond to the socio-economic demands of human beings, and are characterised by an injection of energy in the ecosystems production cycle which is often exceeding the ecological capacity of the ecosystem, i.e. the overall ability of the ecosystem to produce goods and services linked to its bio-physical structure and processes that take place during the agricultural production. Agricultural production is identified as ecosystem service in widely recognised ecosystem service frameworks, but currently there is no clear agreement within the scientific and policy communities on how the ecological-socio-economic flow linked to this provisioning service should be assessed, beyond a mere accounting of yields. This study attempts to provide a new insight to this issue by proposing an approach based on the energy budget, which takes into consideration the energy needed by the ecosystem to supply the service. The approach is based on the concepts of Energy Return on Investment (EROI) and Net Energy Balance (NEB), and considers different bio-physical structures and processes of agroecosystems. The work is structured in three parts: the first aims at estimating inputs (machinery, seeds, fertilizers, irrigation, labour) in energy terms; the second at estimating biomass output in energy terms; the third to compare actual agricultural production with three reference scenarios encompassing a range of human input (no input – low input –high input scenarios). Results show that in general terms cereal and grassland systems have the largest energy gains (both in terms of EROI and NEB). Such systems are characterised by a lower economic value of their output compared to other producing systems such as fruits, which have lower energy gains but a higher embodied energy, which is recognized in the market as valuable. Comparison of actual production systems with the high input scenario confirms that current production in Europe is already highly intensive, and that increasing the energy input would not improve the efficiency of the conversion of such additional energy into biomass. Overall, the proposed approach seems a useful tool to identify which are the factors in the agricultural production process that could be modified to improve the energy efficiency in agricultural systems and the sustainability of their production. This study can be considered as a first step in the assessment of the total energy balance of the agro-ecosystem. In fact it deals with the quantification of energy regarding human inputs and the corresponding output and further analysis should address crucial issues such as the quality of the energy and the embodied energy in the plant production, which will help to better understand the complexity of the agro-ecosystems

Evaluation of Satellite Rainfall Estimates for Drought and Flood Monitoring in Mozambique

Satellite derived rainfall products are useful for drought and flood early warning and overcome the problem of sparse, unevenly distributed and erratic rain gauge observations, provided their accuracy is well known. Mozambique is highly vulnerable to extreme weather events such as major droughts and floods and thus, an understanding of the strengths and weaknesses of different rainfall products is valuable. Three dekadal (10-day) gridded satellite rainfall products (TAMSAT African Rainfall Climatology And Time-series (TARCAT) v2.0, Famine Early Warning System NETwork (FEWS NET) Rainfall Estimate (RFE) v2.0, and Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS)) are compared to independent gauge data (2001–2012). This is done using pairwise comparison statistics to evaluate the performance in estimating rainfall amounts and categorical statistics to assess rain-detection capabilities. The analysis was performed for different rainfall categories, over the seasonal cycle and for regions dominated by different weather systems. Overall, satellite products overestimate low and underestimate high dekadal rainfall values. The RFE and CHIRPS products perform as good, generally outperforming TARCAT on the majority of statistical measures of skill. TARCAT detects best the relative frequency of rainfall events, while RFE underestimates and CHIRPS overestimates the rainfall events frequency. Differences in products performance disappear with higher rainfall and all products achieve better results during the wet season. During the cyclone season, CHIRPS shows the best results, while RFE outperforms the other products for lower dekadal rainfall. Products blending thermal infrared and passive microwave imagery perform better than infrared only products and particularly when meteorological patterns are more complex, such as over the coastal, central and south regions of Mozambique, where precipitation is influenced by frontal systems

Substance-Related Health Problems during Rave Parties in the Netherlands (1997–2008)

The objective of this study was to describe a 12-year (1997–2008) observation of substance-related incidents occurring at rave parties in the Netherlands, including length of visits to first-aid stations, substances used, and severity of the incidents. During rave parties, specifically trained medical and paramedical personnel staffed first aid stations. Visitors were diagnosed and treated, and their data were recorded using standardized methods. During the 12-year period with 249 rave parties involving about 3,800,000 visitors, 27,897 people visited a first aid station, of whom 10,100 reported having a substance-related problem. The mean age of these people was 22.3+/−5.4 years; 52.4% of them were male. Most (66.7%) substance-related problems were associated with ecstasy or alcohol use or both. Among 10,100 substance-related cases, 515 required professional medical care, and 16 of these cases were life threatening. People with a substance-related problem stayed 20 min at the first aid station, which was significantly longer than the 5 min that those without a substance-related health problem stayed. These unique data from the Netherlands identify a variety of acute health problems related to the use of alcohol, amphetamines, cannabis, cocaine, ecstasy, and GHB. Although most problems were minor, people using GHB more often required professional medical care those using the other substances. We recommended adherence to harm and risk reduction policy, and the use of first aid stations with specially trained staff for both minor and serious incidents

Variable loss of functional activities of androgen receptor mutants in patients with androgen insensitivity syndrome

Androgen receptor (AR) mutations in androgen insensitivity syndrome (AIS) are associated with a variety of clinical phenotypes. The aim of the present study was to compare the molecular properties and potential pathogenic nature of 8 novel and 3 recurrent AR variants with a broad variety of functional assays. Eleven AR variants (p.Cys177Gly, p.Arg609Met, p.Asp691del, p.Leu701Phe, p.Leu723Phe, p.Ser741Tyr, p.Ala766Ser, p.Arg775Leu, p.Phe814Cys, p.Lys913X, p.Ile915Thr) were analyzed for hormone binding, transcriptional activation, cofactor binding, translocation to the nucleus, nuclear dynamics, and structural conformation. Ligand-binding domain variants with low to intermediate transcriptional activation displayed aberrant Kd values for hormone binding and decreased nuclear translocation. Transcriptional activation data, FxxFF-like peptide binding and DNA binding correlated well for all variants, except for p.Arg609Met, p.Leu723Phe and p.Arg775Leu, which displayed a relatively higher peptide binding activity. Variants p.Cys177Gly, p.Asp691del, p.Ala766Ser, p.Phe814Cys, and p.Ile915Thr had intermediate or wild type values in all assays and showed a predominantly nuclear localization in living cells. All transcriptionally inactive variants (p.Arg609Met, p.Leu701Phe, p.Ser741Tyr, p.Arg775Leu, p.Lys913X) were unable to bind to DNA and were associated with complete AIS. Three variants (p.Asp691del, p.Arg775Leu, p.Ile915Thr) still displayed significant functional activities in in vitro assays, although the clinical phenotype was associated with complete AIS. The data show that molecular phenotyping based on 5 different functional assays matched in most (70%) but not all cases. Copyrigh

Patients with Biallelic BRCA1/2 Inactivation respond to Olaparib treatment across Histologic tumor types

Purpose: To assess the efficacy of olaparib, a PARP inhibitor (PARPi) in patients with tumors with BRCA1/2 mutations, regardless of histologic tumor type. Patients and Methods: Patients with treatment-refractory BRCA1/2-mutated cancer were included for treatment with offlabel olaparib 300 mg twice daily until disease progression or unacceptable toxicity. In Drug Rediscovery Protocol (DRUP), patients with treatment-refractory solid malignancies receive offlabel drugs based on tumor molecular profiles while whole-genome sequencing (WGS) is performed on baseline tumor biopsies. The primary endpoint was clinical benefit (CB; defined as objective response or stable disease ≥ 16 weeks according to RECIST 1.1). Per protocol patients were enrolled using a Simon-like two-stage model. Results: Twenty-four evaluable patients with nine different tumor types harboring BRCA1/2 mutations were included, 58% had CB from treatment with olaparib. CB was observed in patients with complete loss of function (LoF) of BRCA1/2, while 73% of patients with biallelic BRCA LoF had CB. In 17 patients with and seven without current labeled indication, 10 and four patients had CB, respectively. Treatment resistance in four patients with biallelic loss might be explained by an additional oncogenic driver which was discovered by WGS, including Wnt pathway activation, FGFR amplification, and CDKN2A loss, in three tumor types. Conclusions: These data indicate that using PARPis is a promising treatment strategy for patients with non-BRCA-associated histologies harboring biallelic BRCA LoF. WGS allows to accurately detect complete LoF of BRCA and homologous repair deficiency (HRD) signature as well as oncogenic drivers that may contribute to resistance, using a single assay

Landscape forming processes and diversity of forested landscapes : description and application of the model FORSPACE

In the project "Landschapsvormende processen en biodiversiteit" ("Landscape forming processes and bioversity") the spatial interactions between autonomous development of a vegetation and landscape forming processes were investigated and their implications for (bio)diversity at the landscape level were evaluated. For this purpose the model FORSPACE was developed which is a spatial explicit process model that describes vegetation dynamics and the impacts of landscape forming processes. In this study emphasis was paid to the effects of grazing by large herbivores and fire on the vegetation. Two approaches to analyse diversity at the landscape scale were developed: 1) a spatial analysis evaluating the time-evolution of dominant vegetation types, and 2) a metapopulation approach that describes the population dynamics of indicator species at the landscape scale depending on the availability of habitat. This report focuses on the methodological aspects of the study and thus acts as a reference for future applied studies. The model structure is described in detail, as well as the approach of spatial analysis and of the metapopulation dynamics of an indicator species. Much emphasis is paid on the validation of the driving processes for trees, herbs and grasses by evaluating controlled simulation experiments. In a case-study on the 200 ha of the Imbos, an area in the centre of the Netherlands, the impacts of grazing by herbivores and its interaction with different fire frequencies were evaluated