Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A phase ii study of the italian group for the study of gastrointestinal tract carcinomas (GISCAD)

Background: To evaluate the safety and efficacy of the novel raltitrexed/oxaliplatin combination (TOMOX) as first-line chemotherapy for patients with advanced colorectal cancer. Materials and methods: Previously untreated patients with metastatic colorectal cancer received raltitrexed 3 mg/m2 plus oxaliplatin 100 mg/m2, both intravenously, on day 1 every 3 weeks. Patients were re-evaluated after every third cycle and chemotherapy was continued up to tolerance or disease progression. Results: Fifty-eight patients from 13 Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD) centers were accrued from September 1999 to November 2000. According to the intention-to-treat analysis from 58 patients, the overall response rate was 50% [95% confidence interval (CI) 38% to 62%], with three complete responses and 26 partial responses. The median overall survival (44 patients currently alive) was >9 months and the median time to disease progression was 6.5 months (range 1-15 months). The main hematological toxicity was grade III/IV neutropenia, which occurred in 17% of patients, while anemia and thrombocytopenia were uncommon. Grade III/IV non-hematological toxicities were transient transaminitis (17% of patients); asthenia (16% of patients); neurotoxicity (10% of patients) and diarrhea (7% of patients). No toxic death was observed, one patient with grade IV asthenia after the first cycle refused chemotherapy. Conclusions: The results of this study suggest that the TOMOX combination is an effective and well tolerated regimen for the treatment of advanced colorectal cancer. Its ease of administration and patient tolerance warrant further investigation as an alternative to fluoropyrimidine-based regimens with repeated and prolonged fluorouracil infusions

Near-ground Effect of Height on Pollen Exposure

The effect of height on pollen concentration is not well documented and little is known about the near-ground vertical profile of airborne pollen. This is important as most measuring stations are on roofs, but patient exposure is at ground level. Our study used a big data approach to estimate the near-ground vertical profile of pollen concentrations based on a global study of paired stations located at different heights. We analyzed paired sampling stations located at different heights between 1.5 and 50m above ground level (AGL). This provided pollen data from 59 Hirst-type volumetric traps from 25 different areas, mainly in Europe, but also covering North America and Australia, resulting in about 2,000,000 daily pollen concentrations analyzed. The daily ratio of the amounts of pollen from different heights per location was used, and the values of the lower station were divided by the higher station. The lower station of paired traps recorded more pollen than the higher trap. However, while the effect of height on pollen concentration was clear, it was also limited (average ratio 1.3, range 0.7–2.2). The standard deviation of the pollen ratio was highly variable when the lower station was located close to the ground level (below 10m AGL). We show that pollen concentrations measured at >10m are representative for background near-ground levels

Alternaria Spore Forecasts Using the Atmospheric Dispersion Model SILAM: the First Trial

The SAPID -project of the Academy of Finland aims to add some pest and spore forecasts to the SILAM modelling system. Here we present the first attempt to forecast amounts of Alternaria spores in Europe using the atmospheric dispersion and composition model SILAM, which already includes several pollen types . The final goal after the project is a real operational warning system, which would be able to predict large pest insect migrations and plant pathogen dispersion in regional and continental scales in Europe. Alternaria species are known as major plant pathogens. At least 20% of agricultural spoilage is caused by Alternaria species and the most severe losses may reach up to 80% of yield. Alternaria is also a common allergen in humans and numerical, model based forecasts that specify Alternaria could complement current forecasts. A key tool in this study is the SILAM atmospheric dispersion model. The insect migration and plant pathogen model presented in this study will be constructed as a part of the SILAM modelling system. It includes both Lagrangian and Eulerian advection/diffusion formulations and wet and dry depositions. Spore observations will be used from the University of Turku, the University of Worcester and from the EAN database. The atmospheric dispersion and concentration of spores are predictable using mathematical-physical-biological models in the same way as pollen concentrations are: maps of source areas and flowering parameters with a flowering model in the SILAM constitute pollen emissions. After pollen release, the pollen grains disperse in the air and removal processes remove them from the atmosphere. As a result, the model gives pollen concentrations in the air (see http://silam.fmi.fi). In the case of Alternaria spores, the source areas (e.g. crop fields and grass areas), timing of spore release and favourable weather are the main parameters included in the model. This work demonstrates the possibility and limitations of using the dispersion model with pollen sources for the new type of biogenic aerosols - the Alternaria spores

Predicting sudden cardiac death using common genetic risk variants for coronary artery disease.

AIMS: Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD). METHODS AND RESULTS: A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)]. CONCLUSION: Genetic risk estimate for CAD may also be used to predict SCD

MACC regional multi-model ensemble simulations of birch pollen dispersion in Europe

This paper presents the first ensemble modelling experiment in relation to birch pollen in Europe. The sevenmodel European ensemble of MACC-ENS, tested in trial simulations over the flowering season of 2010, was run through the flowering season of 2013. The simulations have been compared with observations in 11 countries, all members of the European Aeroallergen Network, for both individual models and the ensemble mean and median. It is shown that the models successfully reproduced the timing of the very late season of 2013, generally within a couple of days from the observed start of the season. The end of the season was generally predicted later than observed, by 5 days or more, which is a known feature of the source term used in the study. Absolute pollen concentrations during the season were somewhat underestimated in the southern part of the birch habitat. In the northern part of Europe, a recordlow pollen season was strongly overestimated by all models. The median of the multi-model ensemble demonstrated robust performance, successfully eliminating the impact of outliers, which was particularly useful since for most models this was the first experience of pollen forecasting

Effect of Height on Pollen Sampling in Relation to Pollen Exposure at Ground Level

Pollen monitoring networks around the world are mainly based on rooftop-located stations on buildings. Thus, measured airborne pollen levels could be different from ground level, where most allergic individual reside. Until now, the effects of height of sampling on pollen concentration are not well documented. The aim of this meta-analysis was to analyse these effects using a large number of twin sampling stations. Pollen data from 45 twin-stations Hirst-type volumetric spore traps were analyzed, with a maximum distance of 5km between the twin traps, from 25 different locations. To compare the effect of height, the mean of the daily ratio of the amounts of pollen registrered at different heights was used. The values of the lowest station were divided by the higher station. Stations between 1.5m and 50 agl were considered. The results showed that the traps at lower height registered generally higher pollen concentration (average pollen ratio higher than 1), although the behaviour of the ratio differed per pollen type. For instance, both Poaceae and Betula showed that as the height differenc eincreased, the pollen ratio was higher up to a certain height difference when the ratio stabilizes (around 1.5). On the other hand, the standard deviation of the pollen ratio was greater for the traps closer to ground level. Therefore the height difference is a factor which explains the pollen ratio in conjunction with other variables such as the minimum height of the lower trap or the distance between the spore traps. These findings are highly relevant to clinical practice, as the relationship between pollen exposure at ground level and monitored airborne pollen concentrations at roof-top elvel are determined. Thus, the optimal pollen monitoring height could be optimized based on these result