Higher TIER bumble bees and solitary bees recommendations for a semi-field experimental design

The publication of the proposed EFSA risk assessment guidance document of plant protection products for pollinators highlighted that there are no study designs for non-Apis pollinators available. Since no official guidelines exist for semi-field testing at present, protocols were proposed by the ICPPR non-Apis working group and two years of ring-testing were conducted in 2016 and 2017 to develop a general test set-up. The ringtest design was based on the draft EFSA guidance document, OEPP/EPPO Guideline No. 170 and results of discussions regarding testing solitary bees and bumble bees during the meetings of the ICPPR non-Apis workgroup. Ring-tests were conducted with two different test organisms, one representative of a social bumble bee species (Bombus terrestris L; Hymenoptera, Apidae) and one representative of a solitary bee species (Osmia bicornis L; Hymenoptera, Megachilidae). The species are common species in Europe, commercially available and widely used for pollination services. Several laboratories participated in the higher-tier ring tests. 15 semi-field tests were conducted with bumble bees and 16 semi-field tests were done with solitary bees in 2016 and 2017. Two treatment groups were always included in the ringtests: an untreated control (water treated) and the treatment with dimethoate as a toxic reference item (optional other i.e. brood-affecting substances fenoxycarb or diflubenzuron). The toxic reference items were chosen based on their mode of action and long term experience in honey bee testing. A summary of the ringtest results will be given and the recommendations for the two semi-field test designs will be presented.The publication of the proposed EFSA risk assessment guidance document of plant protection products for pollinators highlighted that there are no study designs for non-Apis pollinators available. Since no official guidelines exist for semi-field testing at present, protocols were proposed by the ICPPR non-Apis working group and two years of ring-testing were conducted in 2016 and 2017 to develop a general test set-up. The ringtest design was based on the draft EFSA guidance document, OEPP/EPPO Guideline No. 170 and results of discussions regarding testing solitary bees and bumble bees during the meetings of the ICPPR non-Apis workgroup. Ring-tests were conducted with two different test organisms, one representative of a social bumble bee species (Bombus terrestris L; Hymenoptera, Apidae) and one representative of a solitary bee species (Osmia bicornis L; Hymenoptera, Megachilidae). The species are common species in Europe, commercially available and widely used for pollination services. Several laboratories participated in the higher-tier ring tests. 15 semi-field tests were conducted with bumble bees and 16 semi-field tests were done with solitary bees in 2016 and 2017. Two treatment groups were always included in the ringtests: an untreated control (water treated) and the treatment with dimethoate as a toxic reference item (optional other i.e. brood-affecting substances fenoxycarb or diflubenzuron). The toxic reference items were chosen based on their mode of action and long term experience in honey bee testing. A summary of the ringtest results will be given and the recommendations for the two semi-field test designs will be presented

Results of 2-Year Ring Testing of a Semifield Study Design to Investigate Potential Impacts of Plant Protection Products on the Solitary Bees Osmia Bicornis and Osmia Cornuta and a Proposal for a Suitable Test Design

There are various differences in size, behavior, and life history traits of non-Apis bee species compared with honey bees (Apis mellifera; Linnaeus, 1758). Currently, the risk assessment for bees in the international and national process of authorizing plant protection products has been based on honey bee data as a surrogate organism for non-Apis bees. To evaluate the feasibility of a semifield tunnel test for Osmia bicornis (Linnaeus, 1758) and Osmia cornuta (Latreille, 1805), a protocol was developed by the non-Apis working group of the International Commission for Plant-Pollinator Relationships, consisting of experts from authorities, academia, and industry. A total of 25 studies were performed over a 2-yr period testing a replicated control against a replicated positive control using either a dimethoate or diflubenzuron treatment. Studies were regarded to be valid, if ≥30% of released females were found to occupy the nesting units in the night/morning before the application (establishment). Thirteen studies were regarded to be valid and were analyzed further. Parameters analyzed were nest occupation, flight activity, cell production (total and per female), cocoon production (total and per female), emergence success, sex ratio, and mean weight of females and males. Dimethoate was a reliable positive control at the tested rate of 75 g a.i./ha, once >30% females had established, displaying acute effects such as reduction in flight activity, increase in adult mortality (shown by nest occupation), and reproduction ability of the females (total cell and cocoon production). On the other hand, no effects on larval and pupal development were observed. The growth regulator diflubenzuron had statistically significant effects on brood development, causing mortality of eggs and larvae at a rate of approximately 200 g a.i./ha, whereas fenoxycarb did not cause any significant effects at the tested rates of 300 and 600 g a.i./ha. In conclusion, the ring-test protocol proved to be adequate once the study comprised a well-established population of female Osmia bees, and the results improved in the second year as the laboratories increased their experience with the test organism. It is noted that the success of a study strongly depends on the experience of the experimenter, the crop quality, the quality of the cocoons, and the weather conditions. Based on these finding, recommendations for a semifield study design with Osmia spp. are proposed. Environ Toxicol Chem 2020;00:1–15.</p

Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first‐line treatment within the randomized Phase III trial FIRE‐3 (AIO KRK‐0306)

Abstract Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE‐3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE‐3 evaluated first‐line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS‐WT tumors (ie, wild‐type in KRAS and NRAS exons 2‐4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13‐2.38; P = .0098) and progression‐free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18‐2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL

The role of neutrophils in equine laminitis

Equine laminitis is a devastating disease in which failure of the adhesion between the digital dermal and epidermal laminae at the basement membrane results in crippling lameness and structural damage to the foot of the horse. Laminitis occurring secondary to sepsis is known to result from a significant inflammatory response that includes leukocyte emigration into the lamellar tissue. These leukocytes, in particular the neutrophil, have been extensively evaluated in experimental models of sepsis-related laminitis in the horse. This review will discuss the relevant findings elucidated from these models and how these findings have affected the development of therapies used to treat this crippling disease