A Fast Parameterized Algorithm for Co-Path Set

The k-CO-PATH SET problem asks, given a graph G and a positive integer k, whether one can delete k edges from G so that the remainder is a collection of disjoint paths. We give a linear-time fpt algorithm with complexity O^*(1.588^k) for deciding k-CO-PATH SET, significantly improving the previously best known O^*(2.17^k) of Feng, Zhou, and Wang (2015). Our main tool is a new O^*(4^{tw(G)}) algorithm for CO-PATH SET using the Cut&Count framework, where tw(G) denotes treewidth. In general graphs, we combine this with a branching algorithm which refines a 6k-kernel into reduced instances, which we prove have bounded treewidth

A practical fpt algorithm for Flow Decomposition and transcript assembly

The Flow Decomposition problem, which asks for the smallest set of weighted paths that "covers" a flow on a DAG, has recently been used as an important computational step in transcript assembly. We prove the problem is in FPT when parameterized by the number of paths by giving a practical linear fpt algorithm. Further, we implement and engineer a Flow Decomposition solver based on this algorithm, and evaluate its performance on RNA-sequence data. Crucially, our solver finds exact solutions while achieving runtimes competitive with a state-of-the-art heuristic. Finally, we contextualize our design choices with two hardness results related to preprocessing and weight recovery. Specifically, $k$-Flow Decomposition does not admit polynomial kernels under standard complexity assumptions, and the related problem of assigning (known) weights to a given set of paths is NP-hard.Comment: Introduces software package Toboggan: Version 1.0. http://dx.doi.org/10.5281/zenodo.82163

Structural Rounding: Approximation Algorithms for Graphs Near an Algorithmically Tractable Class

We develop a framework for generalizing approximation algorithms from the structural graph algorithm literature so that they apply to graphs somewhat close to that class (a scenario we expect is common when working with real-world networks) while still guaranteeing approximation ratios. The idea is to edit a given graph via vertex- or edge-deletions to put the graph into an algorithmically tractable class, apply known approximation algorithms for that class, and then lift the solution to apply to the original graph. We give a general characterization of when an optimization problem is amenable to this approach, and show that it includes many well-studied graph problems, such as Independent Set, Vertex Cover, Feedback Vertex Set, Minimum Maximal Matching, Chromatic Number, (l-)Dominating Set, Edge (l-)Dominating Set, and Connected Dominating Set. To enable this framework, we develop new editing algorithms that find the approximately-fewest edits required to bring a given graph into one of a few important graph classes (in some cases these are bicriteria algorithms which simultaneously approximate both the number of editing operations and the target parameter of the family). For bounded degeneracy, we obtain an O(r log{n})-approximation and a bicriteria (4,4)-approximation which also extends to a smoother bicriteria trade-off. For bounded treewidth, we obtain a bicriteria (O(log^{1.5} n), O(sqrt{log w}))-approximation, and for bounded pathwidth, we obtain a bicriteria (O(log^{1.5} n), O(sqrt{log w} * log n))-approximation. For treedepth 2 (related to bounded expansion), we obtain a 4-approximation. We also prove complementary hardness-of-approximation results assuming P != NP: in particular, these problems are all log-factor inapproximable, except the last which is not approximable below some constant factor 2 (assuming UGC)

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315