Eliminating Hepatitis C Virus From a Prevalent Kidney Transplant Recipient Population: A Single-Center Study in Belgium in the Direct-Acting Antivirals Era

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. Methods: We retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. Results: Out of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P < .001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. Conclusion: Treatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics

Intermittent Surface Oxygenation Results in Similar Mitochondrial Protection and Maintenance of Aerobic Metabolism as Compared to Continuous Oxygenation during Hypothermic Machine Kidney Machine Perfusion

Short bubble and subsequent surface oxygenation is an innovative oxygenation technique and alternative for membrane oxygenation during hypothermic machine perfusion (HMP). The metabolic effect of the interruption of surface oxygenation for 4 h (mimicking organ transport) during HMP was compared to continuous surface and membrane oxygenation in a pig kidney ex situ preservation model. After 30 min of warm ischemia by vascular clamping, a kidney of a ±40 kg pig was procured and subsequently preserved according to one of the following groups: (1) 22-h HMP + intermittent surface oxygenation ( = 12); (2) 22-h HMP + continuous membrane oxygenation ( = 6); and (3) 22-h HMP + continuous surface oxygenation ( = 7). Brief perfusate O uploading before kidney perfusion was either obtained by direct bubble (groups 1, 3) or by membrane (group 2) oxygenation. Bubble oxygenation during minimum 15 min was as efficient as membrane oxygenation in achieving supraphysiological perfusate pO levels before kidney perfusion. Metabolic tissue analysis (i.e., lactate, succinate, ATP, NADH, and FMN) during and at the end of the preservation period demonstrated similar mitochondrial protection between all study groups. Short bubble and subsequent intermittent surface oxygenation of the perfusate of an HMP-kidney might be an effective and cheap preservation strategy to protect mitochondria, eliminating the need/costs of a membrane oxygenator and oxygen source during transport

First Light Measurements with the XMM-Newton Reflection Grating Spectrometers: Evidence for an Inverse First Ionisation Potential Effect and Anomalous Ne A bundance in the Coronae of HR 1099

The RS CVn binary system HR 1099 was extensively observed by the XMM-Newton observatory in February 2000 as its first-light target. A total of 570 ks of exposure time was accumulated with the Reflection Grating Spectrometers (RGS). The integrated X-ray spectrum between 5-35 Angstrom is of unprecedented quality and shows numerous features attributed to transitions of the elements C, N, O, Ne, Mg, Si, S, Fe, and Ni. We perform an in-depth study of the elemental composition of the average corona of this system, and find that the elemental abundances strongly depend on the first ionisation potential (FIP) of the elements. But different from the solar coronal case, we find an inverse FIP effect, i.e., the abundances (relative to oxygen) increase with increasing FIP. Possible scenarios, e.g., selective enrichment due to Ne-rich flare-like events, are discussed.Comment: 5 pages, 4 figures. Accepted by A&A Letters, XMM issu

Growing the Impact of Management Education and Scholarship

Management is not only taught in business schools. For more than 100 years it has also been taught by a special type of university that is ‘more than a business school’. An international group of university leaders trace the emergence, role and future contributions of ‘universities for business and management

Revisiting a fundamental test of the disc instability model for X-ray binaries

We revisit a core prediction of the disc instability model (DIM) applied to X-ray binaries. The model predicts the existence of a critical mass transfer rate, which depends on disc size, separating transient and persistent systems. We therefore selected a sample of 52 persistent and transient neutron star and black hole X-ray binaries and verified if observed persistent (transient) systems do lie in the appropriate stable (unstable) region of parameter space predicted by the model. We find that, despite the significant uncertainties inherent to these kinds of studies, the data are in very good agreement with the theoretical expectations. We then discuss some individual cases that do not clearly fit into this main conclusion. Finally, we introduce the transientness parameter as a measure of the activity of a source and show a clear trend of the average outburst recurrence time to decrease with transientness in agreement with the DIM predictions. We therefore conclude that, despite difficulties in reproducing the complex details of the lightcurves, the DIM succeeds to explain the global behaviour of X-ray binaries averaged over a long enough period of time.Comment: 12 pages, 4 figures. Accepted for publication in MNRAS. Version 2: some typos corrected and references adde

Plant genebanks: present situation and proposals for their improvement. The case of the Spanish Network

[EN] Genebanks were created by the middle of the twentieth century to preserve cultivated biodiversity when landraces began to be substituted by modern varieties. This move was generally accepted as a necessary step to safeguard the future. After about 75 years of collecting and maintaining genetic resources, the increasing ability of biotechnology to create new variability brings the roles of genebanks in the present and near future into question. As a continuation of several workshops that started in 2014, staff of some representative genebanks have met to discuss how the Spanish Plant Genetic Resources Network can be improved, identifying the following major shortcomings: lack of efficient coordination in the distribution of species among genebanks; too many genebanks; existence of detected and undetected duplicates; insufficient rate of regeneration; insufficient phenotyping, genotyping, and epiphenotyping; unsatisfactory rate of use by end users; and, insufficient funding. As a considerable increase in public funding is unlikely, we propose some strategies to increase the efficiency of the system. The most urgent tasks are to strengthen the rationalization of the network by establishing a clear hierarchy and functions, to improve the information in the base collection by deep characterization including not only phenotypes but also uses and utilities, to progressively replace the active collections with focused core collections constructed to meet users' needs, to optimize regeneration protocols, to limit new collecting expeditions of Spanish crop wild relatives to those growing in threatened habitats, and to develop user-friendly platforms to access germplasm documentation, including a unified system of descriptors and classification categories. Current advances in biotechnology, and especially those in gene editing will have without doubt an impact on the role of genebanks. However, the high number of genes and gene combinations created by evolution they hold cannot be produced by these techniques at present. So, these reservoirs of variability will continue to be indispensable for the near-medium future while the function of all the genes is unveiled. In turn, biotechnologies and gene editing will allow us to take advantage of the information held in genebanks in a more efficient and fast way, contributing to a better rationalization and functioning.This work was partially funded Ministerio de Economia y Competitividad and FEDER through projects RFP2015-00008-C4 and RFP2015-00016-00-00.Díez Niclós, MJTDJ.; De La Rosa, L.; Martín, I.; Guasch, L.; Cartea, ME.; Mallor, C.; Casals, J.... (2018). Plant genebanks: present situation and proposals for their improvement. The case of the Spanish Network. Frontiers in Plant Science. 9. https://doi.org/10.3389/fpls.2018.01794S9Ahmed, S., Stepp, J. R., Orians, C., Griffin, T., Matyas, C., Robbat, A., … Kennelly, E. 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A global database for metacommunity ecology, integrating species, traits, environment and space

The use of functional information in the form of species traits plays an important role in explaining biodiversity patterns and responses to environmental changes. Although relationships between species composition, their traits, and the environment have been extensively studied on a case-by-case basis, results are variable, and it remains unclear how generalizable these relationships are across ecosystems, taxa and spatial scales. To address this gap, we collated 80 datasets from trait-based studies into a global database for metaCommunity Ecology: Species, Traits, Environment and Space; “CESTES”. Each dataset includes four matrices: species community abundances or presences/absences across multiple sites, species trait information, environmental variables and spatial coordinates of the sampling sites. The CESTES database is a live database: it will be maintained and expanded in the future as new datasets become available. By its harmonized structure, and the diversity of ecosystem types, taxonomic groups, and spatial scales it covers, the CESTES database provides an important opportunity for synthetic trait-based research in community ecology

Association of Bevacizumab Plus Oxaliplatin-Based Chemotherapy With Disease-Free Survival and Overall Survival in Patients With Stage II Colon Cancer A Secondary Analysis of the AVANT Trial

IMPORTANCE: In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial. OBJECTIVE: To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019. INTERVENTION: Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab. MAIN OUTCOMES AND MEASURES The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC. RESULTS The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4. CONCLUSIONS AND RELEVANCE: In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.