The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent confidence interval 13-32 per cent), in one patient transfused with blood free from leucocytes and platelets (2 per cent, 95 per cent confidence interval 0.05-11 per cent) and in two non-transfused patients (2 per cent, 95 per cent confidence interval 0.3-8 per cent) (P less than 0.01). Natural killer cell function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

Miscanthus is a genus of high‐yielding perennial rhizomatous grasses with C4 photosynthesis. Extensive field trials of Miscanthus spp. biomass production in Europe during the past decade have shown several limitations of the most widely planted clone, M. × giganteus Greef et Deu. A 3‐yr study was conducted at five sites in Europe (Sweden, Denmark, England, Germany, and Portugal) to evaluate adaptation and biomass production potential of four acquisitions of M. × giganteus (No. 1–4) and 11 other genotypes, including M. sacchariflorus (Maxim.) Benth. (No. 5), M. sinensis Andersson (No. 11–15), and hybrids (No. 6–10). At each site, three randomized blocks containing a 5‐ by 5‐m plot of each genotype were established (except in Portugal where there were two blocks) with micropropagated plants at 2 plants m−2. In Sweden and Denmark, only M. sinensis and its hybrids satisfactorily survived the first winter following planting. Mean annual yields across all sites for all surviving genotypes increased each year from 2 t ha−1 dry matter following the first year of growth to 9 and 18 t ha−1 following the second and third year, respectively. Highest autumn yields at sites in Sweden, Denmark, England, and Germany were 24.7 (M. sinensis hybrid no. 8), 18.2 (M. sinensis hybrid no. 10), 18.7 (M. × giganteus no. 3), and 29.1 t ha−1 (M. × giganteus no. 4), respectively. In Portugal, where irrigation was used, the top‐yielding genotype produced 40.9 t ha−1 dry matter (M. sinensis hybrid no. 7). Highest‐yielding genotypes in Sweden and Denmark were among the lowest yielding in Portugal and Germany, demonstrating strong genotype × environment interactions.

Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL-107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in patient-derived xenografts, including melanoma, lung, pancreas and cervical cancer. By eliminating distinct populations in heterogeneous melanoma cell pools, AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth. Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise that rationalized combinatorial targeting of distinct populations in heterogeneous tumors may improve therapeutic effect, and merit clinical validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in mono- or combination therapy.

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SU MMARYThe effects of nitrogen (N) rate and timing on need for fungicide application in winter wheat (Triticum aestivum) were investigated in 3 years of field experiments on loamy sand soils in Denmark. A two-factor completely randomized experimental design was used, comprising seven combinations of different N fertilizer rates and application times, and five doses of fungicide (co-formulation propiconazole and fenpropimorph). Two different varieties of winter wheat with high susceptibility to powdery mildew (Blumeria graminis) were used, Florida in the first season and Pepital in the last two seasons. The severity of powdery mildew and septoria leaf spot (mainly Septoria tritici) varied between seasons from slight to moderate with powdery mildew dominating in the first season and septoria leaf spot in the last season. The severity of both powdery mildew and septoria leaf spot assessed as the Area Under the Disease Progress Curve (AUDPC) was increased by application of N in all years, and more so by early applied N. Grain yields increased with increasing N rate and fungicide dose. However, the observed grain yields did not reveal any Nrfungicide interactions. Regression models were therefore fitted, relating grain yield to rate and timing of N fertilizer and to AUDPC of powdery mildew and septoria leaf spot, and relating AUDPC to rate and timing of N fertilizer and to fungicide dose. They demonstrated that septoria leaf spot had a considerably higher impact on grain yield than mildew. The optimal fungicide dose and N rate were defined as those giving the highest economic return. The regression models were used to estimate the effect of N rate and timing on optimal fungicide dose, and the effect of fungicide application on optimal N rate. The optimal fungicide dose increased almost linearly with N rate above a minimum N rate, but with a large dependency on price relations. Early applied N caused a higher demand for disease control. The fungicide applications in the model were mainly driven by the need to control septoria leaf spot, whereas powdery mildew gave a poor net return for control. The estimated optimal N fertilizer rate for untreated diseased crops was 60 kg N/ha lower than for crops without disease. The use of fungicides with an efficacy twice that of the EBI-fungicides used in this experiment would increase the optimal N rate by c. 20 kg N/ha.

Over the past 3 decades minipigs have moved from being an obscure alternative to dogs and nonhuman primates to being a standard animal model in regulatory toxicity studies. This article covers the use of minipigs as a model in the context of nonclinical drug safety and provides an overview of the minipig's developmental history and relates minipigs to other animal species commonly used in toxicology; and the minipig's translational power is supported by 43 case studies of marketed drug products covered. Special focus is given to criteria for selecting minipigs in nonclinical programs supporting the development of new medicines; the use of swine in the assessment of food additives, agrochemicals, and pesticides; as well as a regulatory perspective on the use of minipigs in Food and Drug Administration (FDA)-regulated products. This article presents the main points conveyed at a symposium held at the 2010 American College of Toxicology meeting in Baltimore, Maryland.

A three factor experiment with winter wheat (Triticum aestivum L.) was carried out during two years on a coarse sandy soil in Denmark. The factors comprised four irrigation strategies including no irrigation, three nitrogen levels providing 67, 83 or 100% of the recommended nitrogen rate, and two strategies for control of leaf diseases (with and without fungicides). Different varieties were used in the two years, Pepital in the first year and Hussar in the second year. Mildew dominated the trial in the first year, but was almost absent in the second year. Septoria occurred in both years, but most severely in the second year. Irrigation increased grain yield, but there were no significant differences between the three strategies, where irrigation was applied. The effect of irrigation on yield was almost solely via an effect of increased transpiration, whereas water use efficiency and harvest index was unaffected. There was a significant interaction for grain yield between irrigation and nitrogen strategies with higher irrigation effects at higher nitrogen rates. This interaction was absent at high disease levels. Increasing nitrogen rate increased grain yield in the second year, but not in the first year. This was attributed to an increasing mildew incidence with increasing nitrogen rate. Irrigation also increased mildew incidence. This caused significant interactions for grain yield between fungicide application and nitrogen rate and between fungicide application and irrigation strategy. Septoria was also significantly affected by both nitrogen and irrigation strategies, but to a lesser degree and not in a consistent manner. The main effect of disease on grain yield was through a reduction in harvest index and a reduction in grain weight. Increasing nitrogen rates slightly reduced harvest index both on a dry matter and on a nitrogen basis. The interaction effects were smaller than the effects of the main factors, and the effect of changes in irrigation or nitrogen strategy on disease incidence could not substitute for the effective disease control obtained by fungicides. The results do, however, indicate possibilities of improving the efficiency of current decision support systems for both fungicide control by better timing of application and irrigation scheduling by reducing water application.

Resistive index measurements are still in a developmental phase. Additional studies are needed before this technique may be used reliably for the diagnosis of obstructive uropathy.