Identification and mapping of a new apple scab resistance gene

Here we report the identification of a new resistance gene (Vd3) against apple scab (Venturia inaequalis) from the apple selection 1980-015-25 of the breeding program at Plant Research International. This accession also contains the Vf gene. We mapped Vd3, using SSR and DArT markers, on linkage group 1, at a distance of 6 cM from Vf gene, but in repulsion phase to Vf. Based on pedigree analysis and resistance tests, it could be deduced that 1980-015-25 had inherited Vd3 from the founder D3. This gene provides resistance to the highly virulent EU-NL-24 strain of the race 7 of V. inaequalis. This strain has overcome the resistance from both Vf and Vg. However, Vd3 has been not effective against the majority of other V. inaequalis strains we used in our disease test

Identification and mapping of the novel apple scab resistance gene Vd3

Apple scab, caused by the fungal pathogen Venturia inaequalis, is one of the most devastating diseases for the apple growing in temperate zones with humid springs and summers. Breeding programs around the world have been able to identify several sources of resistance, the Vf from Malus floribunda 821 being the most frequently used. The appearance of two new races of V. inaequalis (races 6 and 7) in several European countries that are able to overcome the resistance of the Vf gene put in evidence the necessity of the combination of different resistance genes in the same genotype (pyramiding). Here, we report the identification and mapping of a new apple scab resistance gene (Vd3) from the resistant selection “1980-015-25” of the apple breeding program at Plant Research International, The Netherlands. This selection contains also the Vf gene and the novel V25 gene for apple scab resistance. We mapped Vd3 on linkage group 1, 1 cM to the south of Vf in repulsion phase to it. Based on pedigree analysis and resistance tests, it could be deduced that 1980-015-25 had inherited Vd3 from the founder “D3.” This gene provides resistance to the highly virulent EU-NL-24 strain of race 7 of V. inaequalis capable of overcoming the resistance from Vf and Vg

Subgroup effects despite homogeneous heterogeneity test results

Background. Statistical tests of heterogeneity are very popular in meta-analyses, as heterogeneity might indicate subgroup effects. Lack of demonstrable statistical heterogeneity, however, might obscure clinical heterogeneity, meaning clinically relevant subgroup effects. Methods. A qualitative, visual method to explore the potential for subgroup effects was provided by a modification of the forest plot, i.e., adding a vertical axis indicating the proportion of a subgroup variable in the individual trials. Such a plot was used to assess the potential for clinically relevant subgroup effects and was illustrated by a clinical example on the effects of antibiotics in children with acute otitis media. Results. Statistical tests did not indicate heterogeneity in the meta-analysis on the effects of amoxicillin on acute otitis media (Q = 3.29, p = 0.51; I2 = 0%; T2 = 0). Nevertheless, in a modified forest plot, in which the individual trials were ordered by the proportion of children with bilateral otitis, a clear relation between bilaterality and treatment effects was observed (which was also found in an individual patient data meta-analysis of the included trials: p-value for interaction 0.021). Conclusions. A modification of the forest plot, by including an additional (vertical) axis indicating the proportion of a certain subgroup variable, is a qualitative, visual, and easy-to-interpret method to explore potential subgroup effects in studies included in meta-analyse

A recalibrated prediction model can identify level-1 trauma patients at risk of nosocomial pneumonia

Introduction: Nosocomial pneumonia has poor prognosis in hospitalized trauma patients. Croce et al. published a model to predict post-traumatic ventilator-associated pneumonia, which achieved high discrimination and reasonable sensitivity. We aimed to externally validate Croce’s model to predict nosocomial pneumonia in patients admitted to a Dutch level-1 trauma center. Materials and methods: This retrospective study included all trauma patients (≥ 16y) admitted for &gt; 24 h to our level-1 trauma center in 2017. Exclusion criteria were pneumonia or antibiotic treatment upon hospital admission, treatment elsewhere &gt; 24 h, or death &lt; 48 h. Croce’s model used eight clinical variables—on trauma severity and treatment, available in the emergency department—to predict nosocomial pneumonia risk. The model’s predictive performance was assessed through discrimination and calibration before and after re-estimating the model’s coefficients. In sensitivity analysis, the model was updated using Ridge regression. Results: 809 Patients were included (median age 51y, 67% male, 97% blunt trauma), of whom 86 (11%) developed nosocomial pneumonia. Pneumonia patients were older, more severely injured, and underwent more emergent interventions. Croce’s model showed good discrimination (AUC 0.83, 95% CI 0.79–0.87), yet predicted probabilities were too low (mean predicted risk 6.4%), and calibration was suboptimal (calibration slope 0.63). After full model recalibration, discrimination (AUC 0.84, 95% CI 0.80–0.88) and calibration improved. Adding age to the model increased the AUC to 0.87 (95% CI 0.84–0.91). Prediction parameters were similar after the models were updated using Ridge regression. Conclusion: The externally validated and intercept-recalibrated models show good discrimination and have the potential to predict nosocomial pneumonia. At this time, clinicians could apply these models to identify high-risk patients, increase patient monitoring, and initiate preventative measures. Recalibration of Croce’s model improved the predictive performance (discrimination and calibration). The recalibrated model provides a further basis for nosocomial pneumonia prediction in level-1 trauma patients. Several models are accessible via an online tool. Level of evidence: Level III, Prognostic/Epidemiological Study.</p

Sampling strategies for internal validation samples for exposure measurement-error correction: a study of visceral adipose tissue measures replaced by waist circumference measures

Statistical correction for measurement error in epidemiologic studies is possible, provided that information about the measurement error model and its parameters are available. Such information is commonly obtained from a randomly sampled internal validation sample. It is however unknown whether randomly sampling the internal validation sample is the optimal sampling strategy. We conducted a simulation study to investigate various internal validation sampling strategies in conjunction with regression calibration. Our simulation study showed that for an internal validation study sample of 40% of the main study's sample size, stratified random and extremes sampling had a small efficiency gain over random sampling (10% and 12% decrease on average over all scenarios, respectively). The efficiency gain was more pronounced in smaller validation samples of 10% of the main study's sample size (i.e., a 31% and 36% decrease on average over all scenarios, for stratified random and extremes sampling, respectively). To mitigate the bias due to measurement error in epidemiologic studies, small efficiency gains can be achieved for internal validation sampling strategies other than random, but only when measurement error is nondifferential. For regression calibration, the gain in efficiency is, however, at the cost of a higher percentage bias and lower coverage.Clinical epidemiolog

Effectiveness and toxicity of lenvatinib in refractory thyroid cancer:Dutch real-life data

Objective: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods: From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade >= 3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account

Nutrient management on vegetable farms; what will be the future?

Production of field vegetables is known for its high nitrogen input and consequently high nitrogen losses towards the environment. All over the world research tries to find opportunities to reduce these losses. In 2000 the Dutch government initiated and funded a research project (Telen met toekomst) to explore the possibilities to reduce the adverse effects of nitrogen and phosphate inputs on the quality of soil and surface water by farm management. A participatory research approach was chosen, so the farmer, the consultant and scientist work closely together in making annual plans to reach a number of set goals for fertilization on the farm level. By registration of all activities concerning fertilization on the farm, the nitrogen input and output could be monitored. The gap between the reference point at the start of the project and the environmental goals is big for nitrogen: the nitrogen balance surplus on the whole farm level should be reduced from 300 kg N/ha to 90 kg N/ha. First results show that this gap is unlikely to be bridged on all farms within the set period of time, without affecting the farmer's income. However, distinct differences could be observed in the farmers' attitude towards the challenge, the rate of progress varied significantly among farmers

Dutch Environmental Risk Indicator for Plant Protection Products

The NMI 3 focusses on indicators for emissions to surface water and the related aquatic risk resulting from agricultural use of pesticides in the Netherlands. The risk indicator is the exposure toxicity ratio. The model also considers the risk to groundwater, soil organisms and the terrestrial ecosystem. The model calculates indicators for emission to surface water resulting from atmospheric deposition, spray drift, drainage flow, point sources, discharge from greenhouses. The model combines a wide range of information about pesticide sales, usage, spray drift mitigation, emission factors, crop maps, surface water, soil, climate, and substance properties. The primary goal is to compare on a relative scale the annual risk at national scale at the starting and end year of the policy period. The results can be used for ranking, for comparing applications of similar type and for visualisation of spatial patterns of indicators. The result cannot be translated into a risk at a specific location and time