27 research outputs found
Gamma-Ray Bursts: The Underlying Model
A pedagogical derivation is presented of the ``fireball'' model of gamma-ray
bursts, according to which the observable effects are due to the dissipation of
the kinetic energy of a relativistically expanding wind, a ``fireball.'' The
main open questions are emphasized, and key afterglow observations, that
provide support for this model, are briefly discussed. The relativistic outflow
is, most likely, driven by the accretion of a fraction of a solar mass onto a
newly born (few) solar mass black hole. The observed radiation is produced once
the plasma has expanded to a scale much larger than that of the underlying
``engine,'' and is therefore largely independent of the details of the
progenitor, whose gravitational collapse leads to fireball formation. Several
progenitor scenarios, and the prospects for discrimination among them using
future observations, are discussed. The production in gamma- ray burst
fireballs of high energy protons and neutrinos, and the implications of burst
neutrino detection by kilometer-scale telescopes under construction, are
briefly discussed.Comment: In "Supernovae and Gamma Ray Bursters", ed. K. W. Weiler, Lecture
Notes in Physics, Springer-Verlag (in press); 26 pages, 2 figure
No short-cut in assessing trial quality: a case study
Assessing the quality of included trials is a central part of a systematic review. Many check-list type of instruments for doing this exist. Using a trial of antibiotic treatment for acute otitis media, Burke et al., BMJ, 1991, as the case study, this paper illustrates some limitations of the check-list approach to trial quality assessment. The general verdict from the check list type evaluations in nine relevant systematic reviews was that Burke et al. (1991) is a good quality trial. All relevant meta-analyses extensively used its data to formulate therapeutic evidence. My comprehensive evaluation, on the other hand, brought to the surface a series of serious problems in the design, conduct, analysis and report of this trial that were missed by the earlier evaluations. A check-list or instrument based approach, if used as a short-cut, may at times rate deeply flawed trials as good quality trials. Check lists are crucial but they need to be augmented with an in-depth review, and where possible, a scrutiny of the protocol, trial records, and original data. The extent and severity of the problems I uncovered for this particular trial warrant an independent audit before it is included in a systematic review
Association between Literacy, Compliance with Prostate Cancer Screening, and Cancer Aggressiveness: Results from a Brazilian Screening Study
Prognostic and therapeutic impact of neuroendocrine differentiation in prostate adenocarcinoma: an update
An exploratory study of technological knowledge when pupils are designing a programmed technological solution using BBC Micro:bit
Isolation and Characterization of Strains CVO and FWKO B, Two Novel Nitrate-Reducing, Sulfide-Oxidizing Bacteria Isolated from Oil Field Brine
Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma
Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma. Hypoxia reprograms the cellular metabolome and epigenome to promote growth of the most lethal ependymomas