Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts

<p>Abstract</p> <p>Background</p> <p>Histopathological grading of ependymoma has been controversial with respect to its reproducibility and clinical significance. In a 3-phase study, we reviewed the pathology of 229 intracranial ependymomas from European trial cohorts of infants (2 trials - SFOP/CNS9204) and older children (2 trials - AIEOP/CNS9904) to assess both diagnostic concordance among five neuropathologists and the prognostic utility of histopathological variables, particularly tumor grading.</p> <p>Results</p> <p>In phase 1, using WHO criteria and without first discussing any issue related to grading ependymomas, pathologists assessed and independently graded ependymomas from 3 of 4 trial cohorts. Diagnosis of grade II ependymoma was less frequent than grade III, a difference that increased when one cohort (CNS9204) was reassessed in phase 2, during which the pathologists discussed ependymoma grading, jointly reviewed all CNS9204 tumors, and defined a novel grading system based on the WHO classification. In phase 3, repeat independent review of two cohorts (SFOP/CNS9904) using the novel system was associated with a substantial increase in concordance on grading. Extent of tumor resection was significantly associated with progression-free survival (PFS) in SFOP and AIEOP, but not in CNS9204 and CNS9904. Strength of consensus on grade was significantly associated with PFS in only one trial cohort (AIEOP). Consensus on the scoring of individual histopathological features (necrosis, angiogenesis, cell density, and mitotic activity) correlated with PFS in AIEOP, but in no other trial.</p> <p>Conclusions</p> <p>We conclude that concordance on grading ependymomas can be improved by using a more prescribed scheme based on the WHO classification. Unfortunately, this appears to have utility in limited clinical settings.</p

Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes

BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors

Visualizing Big Data with augmented and virtual reality: challenges and research agenda

This paper provides a multi-disciplinary overview of the research issues and achievements in the field of Big Data and its visualization techniques and tools. The main aim is to summarize challenges in visualization methods for existing Big Data, as well as to offer novel solutions for issues related to the current state of Big Data Visualization. This paper provides a classification of existing data types, analytical methods, visualization techniques and tools, with a particular emphasis placed on surveying the evolution of visualization methodology over the past years. Based on the results, we reveal disadvantages of existing visualization methods. Despite the technological development of the modern world, human involvement (interaction), judgment and logical thinking are necessary while working with Big Data. Therefore, the role of human perceptional limitations involving large amounts of information is evaluated. Based on the results, a non-traditional approach is proposed: we discuss how the capabilities of Augmented Reality and Virtual Reality could be applied to the field of Big Data Visualization. We discuss the promising utility of Mixed Reality technology integration with applications in Big Data Visualization. Placing the most essential data in the central area of the human visual field in Mixed Reality would allow one to obtain the presented information in a short period of time without significant data losses due to human perceptual issues. Furthermore, we discuss the impacts of new technologies, such as Virtual Reality displays and Augmented Reality helmets on the Big Data visualization as well as to the classification of the main challenges of integrating the technology.publishedVersionPeer reviewe

Quantitative analysis of intraoperative communication in open and laparoscopic surgery.

BACKGROUND: Communication is important for patient safety in the operating room (OR). Several studies have assessed OR communications qualitatively or have focused on communication in crisis situations. This study used prospective, quantitative observation based on well-established communication theory to assess similarities and differences in communication patterns between open and laparoscopic surgery. METHODS: Based on communication theory, a standardized proforma was developed for assessment in the OR via real-time observation of communication types, their purpose, their content, and their initiators/recipients. Data were collected prospectively in real time in the OR for 20 open and 20 laparoscopic inguinal hernia repairs. Assessors were trained and calibrated, and their reliability was established statistically. RESULTS: During 1,884 min of operative time, 4,227 communications were observed and analyzed (2,043 laparoscopic vs 2,184 open communications). The mean operative duration (laparoscopic, 48 min vs open, 47 min), mean communication frequency (laparoscopic, 102 communications/procedure vs open, 109 communications/procedure), and mean communication rate (laparoscopic, 2.13 communications/min vs open, 2.23 communications/min) did not differ significantly across laparoscopic and open procedures. Communications were most likely to be initiated by surgeons (80-81 %), to be received by either other surgeons (46-50%) or OR nurses (38-40 %), to be associated with equipment/procedural issues (39-47 %), and to provide direction for the OR team (38-46%) in open and laparoscopic cases. Moreover, communications in laparoscopic cases were significantly more equipment related (laparoscopic, 47 % vs open, 39 %) and aimed significantly more at providing direction (laparoscopic, 46 % vs open, 38 %) and at consulting (laparoscopic, 17 % vs open, 12 %) than at sharing information (laparoscopic, 17 % vs open, 31 %) (P &lt; 0.001 for all). CONCLUSIONS: Numerous intraoperative communications were found in both laparoscopic and open cases during a relatively low-risk procedure (average, 2 communications/min). In the observed cases, surgeons actively directed and led OR teams in the intraoperative phase. The lack of communication between surgeons and anesthesiologists ought to be evaluated further. Simple, inexpensive interventions shown to streamline intraoperative communication and teamworking (preoperative briefing, surgeons' mental practice) should be considered further

Information needs in operating room teams: what is right, what is wrong, and what is needed?

BACKGROUND: Safe surgical care requires effective information transfer between members of the operating room (OR) team. The present study aims to assess directly, systematically, and comprehensively, information needs of all OR team-members. METHODS: Thirty-three OR team-members (16 surgeons/anesthesiologists, 17 nurses) took part in a mixed-method interview. Participants indicated what information they need, their problems accessing it, and potential interventions to improve information transfer. They also rated the importance of different sources of information and the quality (accuracy, availability, timeliness, completeness, and clarity) of the information that they typically receive. Theme extraction and statistical analyses (descriptive and inferential) were used to analyze the data. RESULTS: The patient emerged as the top source of information. Surgeons and anesthesiologists relied more on information from fellow clinicians, as well as information originating from diagnostic and imaging labs. They were also more critical about the quality of the information than nursing personnel. Anesthesiologists emerged as the most reliable source of information, whereas information coming from surgeons was deemed lacking in quality (even by surgeons themselves). Finally, the more time participants had spent working in ORs, the more negative views they had about the information that they receive-an unexpected finding. Communication skills training, standardized communication protocols, and information technology (IT) systems to function as a central information repository were the top three proposed interventions. CONCLUSIONS: This study comprehensively maps information sources, problems, and solutions expressed by OR end-users. Recent developments in skills training modules and patient safety interventions for the OR (Surgical Safety Checklist) are discussed as potential interventions that will ameliorate communication in ORs, with a view to enhance patient safety and surgical care

CHARACTERISTICS OF GAMMA-RAY LOUD BLAZARS IN THE VLBA IMAGING AND POLARIMETRY SURVEY

The radio properties of blazars detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope have been observed as part of the VLBA Imaging and Polarimetry Survey. This large, flux-limited sample of active galactic nuclei (AGNs) provides insights into the mechanism that produces strong γ-ray emission. At lower flux levels, radio flux density does not directly correlate with γ-ray flux. We find that the LAT-detected BL Lac objects tend to be similar to the non-LAT BL Lac objects, but that the LAT-detected FSRQs are often significantly different from the non-LAT FSRQs. The differences between the γ-ray loud and quiet FSRQs can be explained by Doppler boosting; these objects appear to require larger Doppler factors than those of the BL Lac objects. It is possible that the γ-ray loud FSRQs are fundamentally different from the γ-ray quiet FSRQs. Strong polarization at the base of the jet appears to be a signature for γ-ray loud AGNs. © 2011. The American Astronomical Society. All rights reserved. Printedin the U.S.A