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- Abramowski, A., et al.
(author)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Journal article (peer-reviewed)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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- Scelo, G, et al.
(author)
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International cancer seminars : a focus on kidney cancer.
- 2016
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:8, s. 1382-5
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Journal article (peer-reviewed)abstract
- Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.
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- Ebrahimi-Fakhari, Darius, et al.
(author)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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In: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Journal article (peer-reviewed)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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- Jacobs, I, et al.
(author)
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Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports : update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).
- 2004
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 110:21, s. 3385-3397
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Journal article (peer-reviewed)abstract
- Outcome after cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002, a task force of the International Liaison Committee on Resuscitation (ILCOR) met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (ie, essential and desirable) data elements recommended by previous Utstein consensus conferences. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, emergency medical services system, and community.
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| 16. |
- Jacobs, I, et al.
(author)
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Update and Simplification of the Utstein Templates for Resuscitation Registries : A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation
- 2004
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In: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 63:3, s. 233-249
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Journal article (peer-reviewed)abstract
- Outcome following cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002 a task force of ILCOR met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (i.e., essential and desirable) data elements recommended by previous Utstein consensus conference. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, EMS system, and community.
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| 20. |
- Perotti, Daniela, et al.
(author)
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Hallmark discoveries in the biology of Wilms tumour
- 2023
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In: Nature Reviews Urology. - 1759-4812.
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Research review (peer-reviewed)abstract
- The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the ‘two-hit’ model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics — from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
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