The fungus Fusarium oxysporum f.sp. cubense (Focub) causes Fusarium wilt of banana. Focub strains are divided into races according to their host specificity, but which virulence factors underlie ...these interactions is currently unknown. In the F. oxysporum f.sp. lycopersici (Fol)-tomato system, small secreted fungal proteins, called Six proteins, were identified in the xylem sap of infected plants. The Fol Six1 protein contributes to virulence and has an avirulence function by activating the I-3 immune receptor of tomato. The Focub tropical race 4 (TR4) genome harbors three SIX1 homologs: SIX1a, b and c. In this study, the role of Focub-SIX1a in pathogenicity was evaluated since this homolog is present in not only TR4 but also in other races. A deletion mutant of the SIX1a gene from Focub TR4 strain II5 was generated (FocubΔSIX1a) and tested in planta. Mutants were found to be severely compromised in their virulence. Ectopic integration of the Focub-SIX1a gene in the FocubΔSIX1a strain restored virulence to wild type levels. We conclude that Focub-SIX1a is required for full virulence of Focub TR4 towards Cavendish banana.
Purpose
The mechanical contribution of plant roots to the soil shear strength is commonly modelled using fibre bundle models (FBM), accounting for sequential breakage of roots. This study provides a ...generic framework, able to includes the many different existing approaches, to quantify the effect of various model assumptions.
Methods
The framework uses (1) a single model parameter determining how load is shared between all roots, (2) a continuous power-law distribution of root area ratio over a range of root diameters, and (3) power-law relationships between root diameters and biomechanical properties. A new load sharing parameter, closely resembling how roots mobilise strength under landslide conditions, is proposed. Exact analytical solutions were found for the peak root reinforcement, thus eliminating the current need for iterative algorithms. Model assumptions and results were validated against existing biomechanical and root reinforcement data.
Results
Root reinforcements proved very sensitive to the user-defined load sharing parameter. It is shown that the current method of discretising all roots in discrete diameter classes prior to reinforcement calculations leads to significant overestimations of reinforcement. Addition of a probabilistic distribution of root failure by means of Weibull survival functions, thus adding a second source of sequential mobilisation, further reduced predicted reinforcements, but only when the reduction due to load sharing was limited.
Conclusion
The presented solutions greatly simplify root reinforcement calculations while maintaining analytical exactness as well as clarity in the assumptions made. The proposed standardisation of fibre bundle-type models will greatly aid comparison and exchange of data.
Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers ...may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.
A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval CI, 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.
Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
The latter are essential for food security in the African Great Lakes Region where banana is a major staple crop that already suffers from manifold other pests and diseases, such as nematodes, ...weevils, Xanthomonas bacterial wilt, and black leaf streak disease, also known as Black Sigatoka. ...sooner or later, every diagnostic will retrieve false positives, such as by a non-TR4 strain that nevertheless tests positive 18. ...multiple diagnostics should be used that target different genomic areas for confirmatory reasons. ...comparative analyses of the genomes from new versus previous incursions enables only provisional associations. ...the proximity of the sampling sites to these farms and the applied disease management practices strongly suggest that TR4 was not successfully contained. ...TR4 was recently reported on Mayotte, an island in the Indian Ocean approximately 700 km from the infested farms in Mozambique 24.
Georeferenced information on road infrastructure is essential for spatial planning, socio-economic assessments and environmental impact analyses. Yet current global road maps are typically outdated ...or characterized by spatial bias in coverage. In the Global Roads Inventory Project we gathered, harmonized and integrated nearly 60 geospatial datasets on road infrastructure into a global roads dataset. The resulting dataset covers 222 countries and includes over 21 million km of roads, which is two to three times the total length in the currently best available country-based global roads datasets. We then related total road length per country to country area, population density, GDP and OECD membership, resulting in a regression model with adjusted R2 of 0.90, and found that that the highest road densities are associated with densely populated and wealthier countries. Applying our regression model to future population densities and GDP estimates from the Shared Socioeconomic Pathway (SSP) scenarios, we obtained a tentative estimate of 3.0-4.7 million km additional road length for the year 2050. Large increases in road length were projected for developing nations in some of the world's last remaining wilderness areas, such as the Amazon, the Congo basin and New Guinea. This highlights the need for accurate spatial road datasets to underpin strategic spatial planning in order to reduce the impacts of roads in remaining pristine ecosystems.
Abstract Objectives High attendance rates in cervical screening are essential for effective cancer prevention. Offering HPV self-sampling to non-responders increases participation rates. The ...objectives of this study were to determine why non-responders do not attend regular screening, and why they do or do not participate when offered a self-sampling device. Methods A questionnaire study was conducted in the Netherlands from October 2011 to December 2012. A total of 35,477 non-responders were invited to participate in an HPV self-sampling study; 5347 women did opt out. Finally, 30,130 women received a questionnaire and self-sampling device. Results The analysis was based on 9484 returned questionnaires (31.5%) with a self-sample specimen, and 682 (2.3%) without. Among women who returned both, the main reason for non-attendance to cervical screening was that they forgot to schedule an appointment (3068; 32.3%). The most important reason to use the self-sampling device was the opportunity to take a sample in their own time-setting (4763; 50.2%). A total of 30.9% of the women who did not use the self-sampling device preferred after all to have a cervical smear taken instead. Conclusions Organisational barriers are the main reason for non-attendance in regular cervical screening. Important reasons for non-responders to the regular screening to use a self-sampling device are convenience and self-control.
Human papillomavirus (HPV) testing on self-collected samples is a potential alternative to HPV testing on clinician-collected samples, but non-inferiority of its clinical accuracy remains to be ...assessed in the regular screening population. The IMPROVE study was done to evaluate the clinical accuracy of primary HPV testing on self-collected samples within an organised screening setting.
In this randomised, non-inferiority trial, women aged 29–61 years were invited to participate in the study as part of their regular screening invitation in the Netherlands. Women who provided informed consent were randomly allocated (1:1, with a block size of ten stratified by age) to one of two groups: a self-sampling group, in which women were requested to collect their own cervicovaginal sample using an Evalyn Brush (Rovers Medical Devices BV, Oss, Netherlands); or a clinician-based sampling group, in which samples were collected by a general practitioner with a Cervex-Brush (Rovers Medical Devices BV). All samples were tested for HPV using the clinically validated GP5+/6+ PCR enzyme immunoassay (Labo Biomedical Products BV, Rijswijk, Netherlands). HPV-positive women in both groups were retested with the other collection method and triaged by cytology and repeat cytology in accordance with current Dutch screening guidelines. Primary endpoints were detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). Non-inferiority of HPV testing on self-collected versus clinician-collected samples was evaluated against a margin of 90% for the relative sensitivity and 98% for the relative specificity. This study is registered at the Dutch Trial register (NTR5078) and has been completed.
Of the 187 473 women invited to participate, 8212 were randomly allocated to the self-sampling group and 8198 to the clinician-based sampling group. After exclusion of women who met the exclusion criteria or who did not return their sample, 7643 women were included in the self-sampling group and 6282 in the clinician-based sampling group. 569 (7·4%) self-collected samples and 451 (7·2%) clinician-collected samples tested positive for HPV (relative risk 1·04 95% CI 0·92–1·17). Median follow-up duration for HPV-positive women was 20 months (IQR 17–22). The CIN2+ sensitivity and specificity of HPV testing did not differ between self-sampling and clinician-based sampling (relative sensitivity 0·96 0·90–1·03; relative specificity 1·00 0·99–1·01). For the CIN3+ endpoint, relative sensitivity was 0·99 (0·91–1·08) and relative specificity was 1·00 (0·99–1·01).
HPV testing done with a clinically validated PCR-based assay had similar accuracy on self-collected and clinician-collected samples in terms of the detection of CIN2+ or CIN3+ lesions. These findings suggest that HPV self-sampling could be used as a primary screening method in routine screening.
Ministry of Health, Welfare, and Sport (Netherlands), and the European Commission.
Combined detection of cell adhesion molecule 1 (CADM1) and T‐lymphocyte maturation‐associated protein (MAL) promoter methylation in cervical scrapes is a promising triage strategy for high‐risk human ...papillomavirus (hrHPV)‐positive women. Here, CADM1 and MAL DNA methylation levels were analysed in cervical scrapes of hrHPV‐positive women with no underlying high‐grade disease, high‐grade cervical intraepithelial neoplasia (CIN) and cervical cancer. CADM1 and MAL methylation levels in scrapes were first related to CIN‐grade of the corresponding biopsy and second to CIN‐grade stratified by the presence of ‘normal’ or ‘abnormal’ cytology as present in the accompanying scrape preceding the cervical biopsy. The scrapes included 167 women with ≤CIN1, 54 with CIN2/3 and 44 with carcinoma. In a separate series of hrHPV‐positive scrapes of women with CIN2/3 (n = 48), methylation levels were related to duration of preceding hrHPV infection (PHI; <5 and ≥5 years). Methylation levels were determined by quantitative methylation‐specific PCR and normal cytology scrapes of hrHPV‐positive women with histologically ≤CIN1 served as reference. CADM1 and MAL methylation levels increased proportional to severity of the underlying lesion, showing an increase of 5.3‐ and 6.2‐fold in CIN2/3, respectively, and 143.5‐ and 454.9‐fold in carcinomas, respectively, compared to the reference. Methylation levels were also elevated in CIN2/3 with a longer duration of PHI (i.e. 11.5‐ and 13.6‐fold, respectively). Moreover, per histological category, methylation levels were higher in accompanying scrapes with abnormal cytology than in scrapes with normal cytology. Concluding, CADM1 and MAL promoter methylation levels in hrHPV‐positive cervical scrapes are related to the degree and duration of underlying cervical disease and markedly increased in cervical cancer.
What's new?
The worse the cervical disease, the more heavily methylated the promoters of two genes, CADM1 and MAL, according to a new study. The authors compared the promoter methylation level of the two genes in hrHPV‐positive cervical scrapes with the CIN‐grade of the underlying disease to try to spot any correlation. Patients with CIN 2/3 had significantly increased promoter methylation of both genes, and those with carcinomas had tremendous increases. Methylation levels also seem to be higher with longer duration of HPV infection, and in hrHPV‐positive cervical scrapes with abnormal cytology. Overall, testing for promoter methylation of CADM1 and MAL in cervical scrapes appears to be quite useful for detecting whether a patient requires treatment for cervical disease.
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