39 research outputs found

    Induced Ramsey-type results and binary predicates for point sets

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    Let kk and pp be positive integers and let QQ be a finite point set in general position in the plane. We say that QQ is (k,p)(k,p)-Ramsey if there is a finite point set PP such that for every kk-coloring cc of (Pp)\binom{P}{p} there is a subset QQ' of PP such that QQ' and QQ have the same order type and (Qp)\binom{Q'}{p} is monochromatic in cc. Ne\v{s}et\v{r}il and Valtr proved that for every kNk \in \mathbb{N}, all point sets are (k,1)(k,1)-Ramsey. They also proved that for every k2k \ge 2 and p2p \ge 2, there are point sets that are not (k,p)(k,p)-Ramsey. As our main result, we introduce a new family of (k,2)(k,2)-Ramsey point sets, extending a result of Ne\v{s}et\v{r}il and Valtr. We then use this new result to show that for every kk there is a point set PP such that no function Γ\Gamma that maps ordered pairs of distinct points from PP to a set of size kk can satisfy the following "local consistency" property: if Γ\Gamma attains the same values on two ordered triples of points from PP, then these triples have the same orientation. Intuitively, this implies that there cannot be such a function that is defined locally and determines the orientation of point triples.Comment: 22 pages, 3 figures, final version, minor correction

    Retroviral transduction of peptide stimulated t cells can generate dual t cell receptor-expressing (bifunctional) t cells reactive with two defined antigens

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    BACKGROUND: Tumors and viruses have developed many mechanisms to evade the immune system, including down-regulation of target antigens and MHC molecules. These immune escape mechanisms may be able to be circumvented by adoptively transferring T cells engineered to express two different T cell receptors, each specific for a different antigen or MHC restriction molecule. METHODS: PBMC from the blood of normal healthy donors were stimulated for three days with an antigenic peptide from cytomegalovirus (CMV) pp65. These CMV reactive cultures were transduced with a encoding the TIL 5 T cell receptor (TCR) that mediates recognition of the dominant epitope of the melanoma antigen MART-1. Following selection for transduced cells, the cultures were evaluated for recognition of CMV pp65 and MART-1 expressing targets. RESULTS: We were able to rapidly create bifunctional T cells capable of recognizing both CMV pp65 and MART-1 using a combination of HLA-A2 tetramer staining and intracellular staining for interferon-γ. These bifunctional T cells were sensitive to very low levels of antigen, recognize MART-1(+ )tumor cells, and maintained their bifunctionality for over 40 days in culture. CONCLUSION: Bifunctional T cells can be engineered by transducing short term peptide stimulated T cell cultures. These bifunctional T cells may be more effective in treating patients with cancer or chronic virus infections because they would reduce the possibility of disease progression due to antigen and/or MHC loss variants

    Locked and Unlocked Chains of Planar Shapes

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    We extend linkage unfolding results from the well-studied case of polygonal linkages to the more general case of linkages of polygons. More precisely, we consider chains of nonoverlapping rigid planar shapes (Jordan regions) that are hinged together sequentially at rotatable joints. Our goal is to characterize the families of planar shapes that admit locked chains, where some configurations cannot be reached by continuous reconfiguration without self-intersection, and which families of planar shapes guarantee universal foldability, where every chain is guaranteed to have a connected configuration space. Previously, only obtuse triangles were known to admit locked shapes, and only line segments were known to guarantee universal foldability. We show that a surprisingly general family of planar shapes, called slender adornments, guarantees universal foldability: roughly, the distance from each edge along the path along the boundary of the slender adornment to each hinge should be monotone. In contrast, we show that isosceles triangles with any desired apex angle less than 90 degrees admit locked chains, which is precisely the threshold beyond which the inward-normal property no longer holds.Comment: 23 pages, 25 figures, Latex; full journal version with all proof details. (Fixed crash-induced bugs in the abstract.

    Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

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    Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy

    Transduction of Human T Cells with a Novel T-Cell Receptor Confers Anti-HCV Reactivity

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    Hepatitis C Virus (HCV) is a major public health concern, with no effective vaccines currently available and 3% of the world's population being infected. Despite the existence of both B- and T-cell immunity in HCV-infected patients, chronic viral infection and HCV-related malignancies progress. Here we report the identification of a novel HCV TCR from an HLA-A2-restricted, HCV NS3:1073–1081-reactive CTL clone isolated from a patient with chronic HCV infection. We characterized this HCV TCR by expressing it in human T cells and analyzed the function of the resulting HCV TCR-transduced cells. Our results indicate that both the HCV TCR-transduced CD4+ and CD8+ T cells recognized the HCV NS3:1073–1081 peptide-loaded targets and HCV+ hepatocellular carcinoma cells (HCC) in a polyfunctional manner with cytokine (IFN-γ, IL-2, and TNF-α) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8− Jurkat cells and CD4+ PBL-derived T cells indicated this TCR was CD8-independent, a property consistent with other high affinity TCRs. HCV TCR-transduced T cells may be promising for the treatment of patients with chronic HCV infections

    Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR

    Head and Neck Cancer Patients: Rates, Reasons, and Risk Factors for 30-Day Unplanned Readmission

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    Objective To analyze rates, risk factors, and complications for 30-day readmission among head and neck cancer (HNC) patients. Methods Retrospective review of administrative records from Vizient (Irving, Texas) Clinical Data Base/Resource Manager on HNC patients who underwent a head and neck surgical procedure from January 2013 through September 2015 at 176 academic and community medical centers. Results Of the 18,121 patients included in the study, 2502 patients were readmitted within 30 days (13.8%). Mean time to readmission was 11 ± 8.2 days. Cancer of the hypopharynx, oropharynx, pharynx, and larynx all had higher odds of readmission compared to oral cavity (odds ratio [OR], 1.8, 1.7, 1.6, and 1.5; 95% confidence interval [CI], 1.4-2.2, 1.4-1.9, 1.2-2.3, and 1.3-1.7, respectively). Consistent with this, flap procedures and laryngectomy had the highest odds of readmission (OR, 1.4 and 1.3; 95% CI, 1.3-1.6 and 1.0-1.5 vs glossectomy, respectively). The most common surgical causes for readmission were postoperative infection (17.6%) and surgical wound dehiscence (16.8%), which most commonly presented on postdischarge days 4 to 5. Acute cardiac events occurred in up to 15.4% of patients depending on complexity of surgery. Dysphagia and electrolyte disturbances were common (15.8% and 15.4%, respectively); patients with these complications typically presented earlier, between days 3 and 4. Discussion Patients with HNC are at high risk of readmission. The cancer subsite and procedure significantly influenced the risk, rate, and reason for readmission. Implications for Practice Findings from this study can help quality improvement and patient safety administrators develop interventions that uniquely target HNC populations

    The Dual Diameter of Triangulations *

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    Abstract Let P be a simple polygon with n vertices. The dual graph T * of a triangulation T of P is the graph whose vertices correspond to the bounded faces of T and whose edges connect those faces of T that share an edge. We consider triangulations of P that minimize or maximize the diameter of their dual graph. We show that both triangulations can be constructed in O(n 3 log n) time using dynamic programming. If P is convex, we show that any minimizing triangulation has dual diameter exactly 2 · log 2 (n/3) or 2 · log 2 (n/3) − 1, depending on n. Trivially, in this case any maximizing triangulation has dual diameter n − 2. Furthermore, we investigate the relationship between the dual diameter and the number of ears (triangles with exactly two edges incident to the boundary of P) in a triangulation. For convex P, we show that there is always a triangulation that simultaneously minimizes the dual diameter and maximizes the number of ears. In contrast, we give examples of general simple polygons where every triangulation that maximizes the number of ears has dual diameter that is quadratic in the minimum possible value. We also consider the case of point sets in general position in the plane. We show that for any such set of n points there are triangulations with dual diameter in O(log n) and in Ω( √ n)
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