1,109 research outputs found

    Between Treewidth and Clique-width

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    Many hard graph problems can be solved efficiently when restricted to graphs of bounded treewidth, and more generally to graphs of bounded clique-width. But there is a price to be paid for this generality, exemplified by the four problems MaxCut, Graph Coloring, Hamiltonian Cycle and Edge Dominating Set that are all FPT parameterized by treewidth but none of which can be FPT parameterized by clique-width unless FPT = W[1], as shown by Fomin et al [7, 8]. We therefore seek a structural graph parameter that shares some of the generality of clique-width without paying this price. Based on splits, branch decompositions and the work of Vatshelle [18] on Maximum Matching-width, we consider the graph parameter sm-width which lies between treewidth and clique-width. Some graph classes of unbounded treewidth, like distance-hereditary graphs, have bounded sm-width. We show that MaxCut, Graph Coloring, Hamiltonian Cycle and Edge Dominating Set are all FPT parameterized by sm-width

    Solving Problems on Graphs of High Rank-Width

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    A modulator of a graph G to a specified graph class H is a set of vertices whose deletion puts G into H. The cardinality of a modulator to various tractable graph classes has long been used as a structural parameter which can be exploited to obtain FPT algorithms for a range of hard problems. Here we investigate what happens when a graph contains a modulator which is large but "well-structured" (in the sense of having bounded rank-width). Can such modulators still be exploited to obtain efficient algorithms? And is it even possible to find such modulators efficiently? We first show that the parameters derived from such well-structured modulators are strictly more general than the cardinality of modulators and rank-width itself. Then, we develop an FPT algorithm for finding such well-structured modulators to any graph class which can be characterized by a finite set of forbidden induced subgraphs. We proceed by showing how well-structured modulators can be used to obtain efficient parameterized algorithms for Minimum Vertex Cover and Maximum Clique. Finally, we use well-structured modulators to develop an algorithmic meta-theorem for deciding problems expressible in Monadic Second Order (MSO) logic, and prove that this result is tight in the sense that it cannot be generalized to LinEMSO problems.Comment: Accepted at WADS 201

    Prognostic Significance of Negative Lymph Node Long Axis in Esophageal Cancer: Results From the Randomized Controlled UK MRC OE02 Trial

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    OBJECTIVE: To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients. BACKGROUND: Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size. METHODS: The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed. RESULTS: Large LNneg size was related to lower pN category (P = 0.01) and lower frequency of lymphatic invasion (P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size (P < 0.001). Large LNneg contained less lymphocytes (P = 0.02) and had a higher germinal centers/lymphocyte ratio (P = 0.05). CONCLUSIONS: This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms

    The Cancer Hub Approach for Upper Gastrointestinal Surgery During COVID-19 Pandemic: Outcomes from a UK Cancer Centre.

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    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to increase intensive care capacity. Our unit instituted the 'RM Partners Cancer Hub' at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a 'COVID-lite' setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period. METHODS: From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted. RESULTS: A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae. CONCLUSION: Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption

    Medical theses as part of the scientific training in basic medical and dental education: experiences from Finland

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    <p>Abstract</p> <p>Background</p> <p>Teaching the principles of scientific research in a comprehensive way is important at medical and dental schools. In many countries medical and dental training is not complete until the candidate has presented a diploma thesis. The objective of this study was to evaluate the nature, quality, publication pattern and visibility of Finnish medical diploma theses.</p> <p>Methods</p> <p>A total of 256 diploma theses presented at the University of Oulu from 2001 to 2003 were analysed. Using a standardised questionnaire, we extracted several characteristics from each thesis. We used the name of the student to assess whether the thesis resulted in a scientific publication indexed in medical article databases. The number of citations received by each published thesis was also recorded.</p> <p>Results</p> <p>A high proportion of the theses (69.5%) were essentially statistical in character, often combined with an extensive literature review or the development of a laboratory method. Most of them were supervised by clinical departments (55.9%). Only 61 theses (23.8%) had been published in indexed scientific journals. Theses in the fields of biomedicine and diagnostics were published in more widely cited journals. The median number of citations received per year was 2.7 and the range from 0 to 14.7.</p> <p>Conclusion</p> <p>The theses were seldom written according to the principles of scientific communication and the proportion of actually published was small. The visibility of these theses and their dissemination to the scientific community should be improved.</p

    Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

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    Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

    Effect of pathologic tumor response and nodal status on survival in the medical research council adjuvant gastric infusional chemotherapy trial

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    Purpose: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods: Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results: Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion: Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate

    Quasi-Normal Modes of Stars and Black Holes

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    Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

    Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

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    BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721
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