Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but falling short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 84% of patients, with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials

A comparison of drug transport in pulmonary absorption models: isolated perfused rat lungs, respiratory epithelial cell lines and primary cell culture

Purpose: To evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo. Method: The permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo. Results: A strong relationship was observed between the logarithm of the in vivo absorption half-life and the absorption half-life in the IPL (r = 0.97; excluding formoterol). Good log-linear relationships were also found between the apparent first-order absorption rate in vivo and cell layer permeability with correlation coefficients of 0.92, 0.93, 0.91 in Calu-3, 16HBE14o- and NHBE cells, respectively. Conclusion: The simple IPL technique provided a good prediction of drug absorption from the lungs, making it a useful method for empirical screening of drug absorption in the lungs. Permeability measurements were similar in all the respiratory epithelial cell models evaluated, with Calu-3 having the advantage for routine permeability screening purposes of being readily availability, robust and easy to culture

Gamma-Ray Pulsars

Gamma-ray photons from young pulsars allow the deepest insight into the properties and interactions of high-energy particles with magnetic and photon fields in a pulsar magnetosphere. Measurements with the Compton Gamma-Ray Observatory have led to the detection of nearly ten gamma-ray pulsars. Although quite a variety of individual signatures is found for these pulsars, some general characteristics can be summarized: (1) the gamma-ray lightcurves of most high-energy pulsars show two major peaks with the pulsed emission covering more than 50% of the rotation, i.e. a wide beam of emission; (2) the gamma-ray spectra of pulsars are hard (power law index less than 2), often with a luminosity maximum around 1 GeV. A spectral cutoff above several GeV is found; (3) the spectra vary with rotational phase indicating different sites of emission; and (4) the gamma-luminosity scales with the particle flux from the open regions of the magnetosphere (Goldreich-Julian current).Comment: 9 pages, 9 figures, 2 tables. To appear in the Proceedings of the 270. WE-Heraeus Seminar on Neutron Stars, Pulsars and Supernova Remnants, Jan. 21-25, 2002, Physikzentrum Bad Honnef, eds W. Becker, H. Lesch & J. Truemper. Proceedings are available as MPE-Report 27

Accuracy of the ABC/2 score for intracerebral hemorrhage: systematic review and analysis of MISTIE, CLEAR-IVH, and CLEAR III

Background and Purpose: The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography–based planimetry (CTP). p>Methods:In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. Results: In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC (r2=0.93) than with site-ABC (r2=0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm3; CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P Conclusions: ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots.</p

Restorative justice in Belgian prisons: The results of an empirical research

peer reviewedJustice–when spelled with a capital 'J’ – should be discursive [31] and based on equal respect ([40]: 206, 210) allowing a plurality of voices within the discourse. Particularly in the present research, this thread of pluralism is important. Prisoners’ voices have rarely been heard. Yet, if we wish to be true to the principle that restorative justice is discursive, it follows that the discourse is not complete without also accommodating their voices. To date, little research attention has been paid to the inner motivations of imprisoned offenders for willing to participate in restorative justice initiatives, as well as to their perceptions about their relationships with the victim and the community and the impact of religion on them. Hence, the present empirical study, conducted in several prisons across Belgium, endeavours to shed light on these aspects that have been theoretically overlooked, providing valuable information at policy-level about the design of future restorative justice programmes