Weighted pseudo-values for partly unobserved group membership in paediatric stem cell transplantation studies

Generalised pseudo-values have been suggested to evaluate the impact of allogeneic stem cell transplantation on childhood leukaemia. The approach compares long-term survival of two cohorts defined by the availability or non-availability of suitable donors for stem cell transplantation. A patient's cohort membership becomes known only after completed donor search with or without an identified donor. If a patient suffers an event during donor search, stem cell transplantation will no longer be indicated. In such a case, donor search will be ceased and cohort membership will remain unknown. The generalised pseudo-values approach considers donor identification as binary time-dependent covariate and uses inverse-probability-of-censoring weighting to adjust for non-identified donors. The approach leads to time-consuming computations due to multiple redefinitions of the risk set for pseudo-value calculation and an explicit adjustment for waiting-time bias. Here, the problem is looked at from a different angle. By considering the probability that a donor would have been identified after ceasing of donor search, weights for common pseudo-values are defined. This leads to a faster alternative approach as only a single risk set is necessary. Extensive computer simulations show that both, the generalised and the new weighted pseudo-values approach, provide approximately unbiased estimates. Confidence interval coverage is satisfactory for typical clinical scenarios. In situations, where donor identification takes considerably longer than usual, the weighted pseudo-values approach is preferable. Both approaches complement each other as they have different potential in addressing further aspects of the underlying medical question.

Genetics and Breeding of Heat Tolerance in Rice

Extreme weather events, especially heat waves, have become more frequent with global warming. High temperature significantly affects world food security by decreasing crop yield. Rice is intensively planted in tropical and subtropical areas in Asia, where high temperature has become a major factor affecting rice production. Rice is sensitive to high temperature, especially at booting and flowering stages. Rice varieties tolerant of high temperature are rare, and only a few heat-tolerant rice varieties have been identified. High temperature at booting and flowering stages causes sterile pollen, decreased pollen shedding, and poor pollen germination, which finally lead to a yield decrease. Heat-tolerant QTLs have been identified in different studies, but new breeding lines with considerable heat tolerance have not been bred using identified heat-tolerance donors and QTLs. Research on heat-tolerant donor identification, QTL mapping, gene cloning, and large-scale phenotyping technology is important for developing heat-tolerant rice varieties.

Implementing of Active Brain-Dead Donor Identification Strategy in a Single Donor Center: One Year Experience

Background and objectives: Organ shortage is considered to be a major limitation for increasing transplantation rates. Brain-dead donors (DBDs) are an important source of organs, but up to 50% of potential DBDs might not be identified. An active brain-dead donor search could potentially increase a deceased donor pool. The aim of this study was to evaluate the effectiveness of an active potential DBD identification program and to evaluate one year impact on the potential organ donor pool in Lithuania‘s biggest medical institution. Materials and Methods: An organ donor coordinator service was established and active DBD search strategy was implemented in the hospital of LSMU Kauno Klinikos, and retrospective data analysis was performed between December 2016 and December 2017. Collected data was compared to the available data of the previous year in the same center and to the donation dynamics of the whole country. Results: A total of 6734 patients were treated in all intensive care units (ICU), and 234 (3.5%) of them were identified as possible donors. No increase in potential donor’s number was observed in study year (n = 34) compared to remote year (n = 37). No significant difference in potential donor’s demographic data, cause of death, family refusals and medical contraindication rates. Cerebral angiography (CA) repeated in 20% of potential donors in order to confirm brain death diagnosis. More potential donors for whom CA was repeated had decompressive craniectomy done (66.7% vs. 33.3%, p = 0.018). Decompressive craniectomy statistically significantly increases the rate of repeated CA (OR 12.7; 95% CI, 1.42–113.37; p = 0.023). Active search strategy increased length of hospital stay of potential donors comparing to previous year (3.97 ± 4.73 vs. 2.51 ± 2.63, p = 0.003). An optimal time of the first four days of hospitalization to identify a potential donor was observed during our study (OR 10.42; 95% CI, 4.29–25.34; p = 0.001). Conclusions: We were not able to demonstrate active donor identification strategy superiority over the passive strategy during a short one year period; nevertheless, valuable knowledge was gained in brain death diagnostics, new terminology was implemented, and the stability of actual donor numbers was observed in the experimental donor center in the light of decreasing national results. Long-term strategy is required to achieve sustainable results in organ donation.

Rapid Donor Identification Improves Survival in High-Risk First-Remission Patients With Acute Myeloid Leukemia

PURPOSE: Patients with acute myeloid leukemia with high-risk cytogenetics in first complete remission (CR1) achieve better outcomes if they undergo allogeneic hematopoietic cell transplantation (HCT) compared with consolidation chemotherapy alone. However, only approximately 40% of such patients typically proceed to HCT. METHODS: We used a prospective organized approach to rapidly identify donors to improve the allogeneic HCT rate in adults with high-risk acute myeloid leukemia in CR1. Newly diagnosed patients had cytogenetics obtained at enrollment, and those with high-risk cytogenetics underwent expedited HLA typing and were encouraged to be referred for consultation with a transplantation team with the goal of conducting an allogeneic HCT in CR1. RESULTS: Of 738 eligible patients (median age, 49 years; range, 18-60 years of age), 159 (22%) had high-risk cytogenetics and 107 of these patients (67%) achieved CR1. Seventy (65%) of the high-risk patients underwent transplantation in CR1 ( P < .001 compared with the historical rate of 40%). Median time to HCT from CR1 was 77 days (range, 20-356 days). In landmark analysis, overall survival (OS) among patients who underwent transplantation was significantly better compared with that of patients who did not undergo transplantation (2-year OS, 48% v 35%, respectively [ P = .031]). Median relapse-free survival after transplantation in the high-risk cohort who underwent transplantation in CR1 (n = 70) was 11.5 months (range, 4-47 months), and median OS after transplantation was 14 months (range, 4-44 months). CONCLUSION: Early cytogenetic testing with an organized effort to identify a suitable allogeneic HCT donor led to a CR1 transplantation rate of 65% in the high-risk group, which, in turn, led to an improvement in OS when compared with the OS of patients who did not undergo transplantation.

Where did you come from, where did you go: Refining Metagenomic Analysis Tools for HGT characterisation

Horizontal gene transfer (HGT) has changed the way we regard evolution. Instead of waiting for the next generation to establish new traits, especially bacteria are able to take a shortcut via HGT that enables them to pass on genes from one individual to another, even across species boundaries. Existing HGT detection approaches usually first identify genes of foreign nature, e.g., using composition-based methods, and then exploit phylogenetic discrepancies of the corresponding gene tree compared to a species tree. These approaches depend on fully sequenced HGT organisms and computable phylogenetic species trees. The tool Daisy offers a different approach based on read mapping that provides complementary evidence compared to existing methods at the cost of relying on the acceptor and donor references of the HGT organism being known. Acceptor and donor identification is akin to species identification in metagenomic samples based on sequencing reads, a problem addressed by metagenomic profiling tools. However, acceptor and donor references have certain properties such that these methods can not be directly applied. We propose DaisyGPS, a mapping-based pipeline that is able to identify acceptor and donor candidates of an HGT organism based on sequencing reads. To do that, DaisyGPS leverages metagenomic profiling strategies and refines them for HGT candidate identification. These candidates can then be further evaluated by tools like Daisy to establish HGT regions. We successfully validated our approach on both simulated and real data, and show its benefits in an investigation of MRSA outbreak data. DaisyGPS is freely available from https://gitlab.com/rki_bioinformatics/.