Limited predictive value of FDG-PET for response assessment in the preoperative treatment of esophageal cancer : results of a prospective multi-center trial (SAKK 75/02)

BACKGROUND: Only responding patients benefit from preoperative therapy for locally advanced esophageal carcinoma. Early detection of non-responders may avoid futile treatment and delayed surgery. PATIENTS AND METHODS: In a multi-center phase ll trial, patients with resectable, locally advanced esophageal carcinoma were treated with 2 cycles of induction chemotherapy followed by chemoradiotherapy (CRT) and surgery. Positron emission tomography with 2[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) was performed at baseline and after induction chemotherapy. The metabolic response was correlated with tumor regression grade (TRG). A decrease in FDG tumor uptake of less than 40% was prospectively hypothesized as a predictor for histopathological non-response (TRG < 2) after CRT. RESULTS: 45 patients were included. The median decrease in FDG tumor uptake after chemotherapy correlated well with TRG after completion of CRT (p = 0.021). For an individual patient, less than 40% decrease in FDG tumor uptake after induction chemotherapy predicted histopathological non-response after completion of CRT, with a sensitivity of 68% and a specificity of 52% (positive predictive value 58%, negative predictive value 63%). CONCLUSIONS: Metabolic response correlated with histopathology after preoperative therapy. However, FDG-PET did not predict non-response after induction chemotherapy with sufficient clinical accuracy to justify withdrawal of subsequent CRT and selection of patients to proceed directly to surgery

Vegetational and agricultural dynamics at Burgäschisee (Swiss Plateau) recorded for 18,700 years by multi-proxy evidence from partly varved sediments

Little is known about the timing and the vegetation dynamics shortly after the Last Glacial Maximum (LGM) on the Swiss Plateau 19,000–15,000 cal BP. Subsequent Late Glacial and Holocene vegetation changes are better known; however, it is unclear if the few available palynological and macrofossil records are able to capture the entire vegetation variability of the region. A new palaeoecological multi-proxy study using pollen, spores, charcoal and X-ray fluorescence (XRF) from Burgäschisee (Swiss Plateau, 465 m a.s.l.) is applied to reconstruct vegetation, fire and land use for the past 19,000 cal years. Steppe tundra vegetation established at c. 18,700 cal BP only c. 300 years after the end of the LGM and deglaciation. A shift from steppe tundra (Artemisia, Helianthemum) to shrub tundra (Betula nana, Salix, Juniperus) with sporadic tree Betula stands occurred around 16,000 cal BP, most likely in response to climate warming after the end of Heinrich event 1. Abundant spores of coprophilous fungi (Sporormiella, Cercophora) may reflect the presence of Pleistocene large herbivores (e.g. Mammuthus primigenius, Bison bonasus, Rangifer tarandus). Afforestation started more than 2,000 years later with Juniperus and tree Betula around 14,500 cal BP. Mixed Betula and Pinus sylvestris forests persisted until 10,800 cal BP, when mixed elm forests expanded into the region in response to climate warming. Around 8,200 cal BP, mesophilous Fagus sylvatica and Abies alba partly replaced more heliophilous species in the forests, when climate became less continental and more moist. Pollen of Cerealia, Plantago lanceolata and other crops and weeds suggest that agricultural activities became significant during the Neolithic around 6,500 cal BP (4550 cal BC). Archaeological findings from Neolithic pile dwellings around 5,950 cal BP (4000 cal BC) indicate local settlements around the lake. The lake sediments are laminated for most of the last c. 6,800 years. With two independent proxies (XRF and pollen), we can demonstrate that these laminations are annual, suggesting short-term mixing of the lake water due to a more open landscape in response to land use. Our study shows that the annually laminated (varved) sediments from Burgäschisee have a great potential for high-resolution multi-proxy analyses covering the past c. 6,800 years. They can provide accurate ages of cultural phases that might be compared with dendrochronologically dated evidence from lake dwellings

Recommendations for the Assessment of Potential Environmental Effects of Genome-Editing Applications in Plants in the EU

The current initiative of the European Commission (EC) concerning plants produced using certain new genomic techniques, in particular, targeted mutagenesis and cisgenesis, underlines that a high level of protection for human and animal health and the environment needs to be maintained when using such applications. The current EU biosafety regulation framework ensures a high level of protection with a mandatory environmental risk assessment (ERA) of genetically modified (GM) products prior to the authorization of individual GMOs for environmental release or marketing. However, the guidance available from the European Food Safety Authority (EFSA) for conducting such an ERA is not specific enough regarding the techniques under discussion and needs to be further developed to support the policy goals towards ERA, i.e., a case-by-case assessment approach proportionate to the respective risks, currently put forward by the EC. This review identifies important elements for the case-by-case approach for the ERA that need to be taken into account in the framework for a risk-oriented regulatory approach. We also discuss that the comparison of genome-edited plants with plants developed using conventional breeding methods should be conducted at the level of a scientific case-by-case assessment of individual applications rather than at a general, technology-based level. Our considerations aim to support the development of further specific guidance for the ERA of genome-edited plants

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (∣r̂ g∣ ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (∣r̂ g∣ ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.</p