Fatal airway disease in an adult with chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) is a syndrome of disordered immunity in which a variety of opportunistic respiratory infections have been documented. Restrictive pulmonary disease without advanced fibrotic changes has been also known to occur; obstructive lower airways disease related to chronic GVHD has apparently not been referred to. We report a patient with chronic GVHD and irreversible airways obstruction who died in respiratory failure caused by generalised bronchiolar damage progressing over a few months. Lung function studies showed severe airflow limitation and a leftward shift in the pressure-volume curve indicating a loss of elastic recoil pressure. Postmortem pulmonary lesions were consistent with a necrotising obliterative bron chiolitis. Our purpose is to describe this unusual complication not previously reported in chronic GVHD and discuss the pulmonary mechanics

The Cherenkov Telescope Array Large Size Telescope

The two arrays of the Very High Energy gamma-ray observatory Cherenkov Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA to achieve a low-energy threshold of 20 GeV, which is critical for important studies in astrophysics, astroparticle physics and cosmology. This work presents the key specifications and performance of the current LST design in the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality

Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a multivariate analysis of risk factors

Objectives: bone marrow transplantation is still associated with a high case-fatality rate. This study was conducted to identify the risk factors for early mortality in acute lymphocytic leukaemia patients treated with bone marrow transplantation. Methods: prospectively collected data on 76 acute lymphocytic leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive days, before (32 patients) or after (44 patients) total body irradiation who received an allogeneic (56 patients) or autologous (20 patients) bone marrow transplantation were considered in the multivariate analysis including fifteen potentially prognostic variables for early mortality. Results: in the entire group, patients older than 20 years had a relative risk for early mortality of 3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI: 1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55 (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus-host disease. Among radiation therapy variables only dose-rate showed a trend towards better prognosis in patients treated with less than 5 cGy/min. Conclusions: in our patients and within the range of treatment variables studied, age, Karnofsky index, and graft-versus-host disease are the most important factors related with early mortality

Inflammatory myopathy associated with chronic graft-versus-host disease

Damage of skeletal muscle in association with graft-versus-host disease (GvHD) has been referenced exceptionally. Eighteen months after bone marrow transplantation, a 22-year-old man developed polymyositis associated with manifestations of chronic GvHD, such as peripheral eosinophilia and localized morphea. Diagnosis of polymyositis was established by clinical, electromyographic, and histopathologic findings. His clinical condition improved with immunosuppressive therapy. At electronmicroscopy, some close and broad contacts between lymphocytes with activated appearance and degenerated muscle fibers were observed, suggesting a lymphocytotoxic mechanism. The findings support the idea that polymyositis can be considered a manifestation of chronic GvHD

Cadherin-13, a Mediator of Calcium-Dependent Cell-Cell Adhesion, Is Silenced by Methylation in Chronic Myeloid Leukemia and Correlates With Pretreatment Risk Profile and Cytogenetic Response to Interferon Alfa

Purpose: Cadherin-13 (CDH13) is a newly characterized cadherin molecule responsible for selective cell recognition and adhesion, the expression of which is decreased by methylation in a variety of human cancers, indicating that the CDH13 gene functions as a tumor suppressor gene. Although defective progenitor-stromal adhesion is a well-recognized feature of chronic myeloid leukemia (CML), the role of CDH13 abnormalities has not been evaluated in this disease. Patients and Methods: We examined the methylation status of the CDH13 promoter in 179 chronic phase (CP)-CML patients and in 52 advanced-phase samples and correlated it with mRNA expression using methylation-specific polymerase chain reaction (PCR) and reverse transcriptase PCR. Results: Aberrant de novo methylation of the CDH13 promoter region was observed in 99 (55%) of 179 of CP-CML patients, and 90 of the patients failed to express CDH13 mRNA (P < .0001). Advanced-stage samples (n = 52) showed concordant methylation results with their corresponding CP tumors, indicating that CDH13 methylation was not acquired during the course of the disease. Nevertheless, absence of CDH13 expression was more frequently observed among Sokal high-risk patients (P = .01) and was also independently associated with a shorter median progression-free survival time (P = .03) and poor cytogenetic response to interferon alfa treatment (P = .0001). Conclusion: Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease

The T2K experiment

The T2K experiment is a long baseline neutrino oscillation experiment. Its main goal is to measure the last unknown lepton sector mixing angle θ13 by observing νe appearance in a νμ beam. It also aims to make a precision measurement of the known oscillation parameters, and sin22θ23, via νμ disappearance studies. Other goals of the experiment include various neutrino cross-section measurements and sterile neutrino searches. The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC. This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem