Theorising Disability: Beyond Common Sense

This article seeks to introduce the topic of disability to political theory via a discussion of some of the literature produced by disability theorists. The author argues that these more radical approaches conceptualise disability in ways that conflict with ‘common-sense’ notions of disability that tend to underpin political theoretical considerations of the topic. Furthermore, the author suggests that these more radical conceptualisations have profound implications for current debates on social justice, equality and citizenship that highlight the extent to which these notions are also currently underpinned by ‘common-sense’ notions of ‘normality’

A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor’s response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2–3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance

Theoretical overview on high-energy emission in microquasars

Microquasar (MQ) jets are sites of particle acceleration and synchrotron emission. Such synchrotron radiation has been detected coming from jet regions of different spatial scales, which for the instruments at work nowadays appear as compact radio cores, slightly resolved radio jets, or (very) extended structures. Because of the presence of relativistic particles and dense photon, magnetic and matter fields, these outflows are also the best candidates to generate the very high-energy (VHE) gamma-rays detected coming from two of these objects, LS 5039 and LS I +61 303, and may be contributing significantly to the X-rays emitted from the MQ core. In addition, beside electromagnetic radiation, jets at different scales are producing some amount of leptonic and hadronic cosmic rays (CR), and evidences of neutrino production in these objects may be eventually found. In this work, we review on the different physical processes that may be at work in or related to MQ jets. The jet regions capable to produce significant amounts of emission at different wavelengths have been reduced to the jet base, the jet at scales of the order of the size of the system orbital semi-major axis, the jet middle scales (the resolved radio jets), and the jet termination point. The surroundings of the jet could be sites of multiwavelegnth emission as well, deserving also an insight. We focus on those scenarios, either hadronic or leptonic, in which it seems more plausible to generate both photons from radio to VHE and high-energy neutrinos. We briefly comment as well on the relevance of MQ as possible contributors to the galactic CR in the GeV-PeV range.Comment: Astrophysics & Space Science, in press (invited talk in the conference: The multimessenger approach to the high-energy gamma-ray sources", Barcelona/Catalonia, in July 4-7); 10 pages, 6 figures, 2 tables (one reference corrected

A New Approach to Searching for Dark Matter Signals in Fermi-LAT Gamma Rays

Several cosmic ray experiments have measured excesses in electrons and positrons, relative to standard backgrounds, for energies from ~ 10 GeV - 1 TeV. These excesses could be due to new astrophysical sources, but an explanation in which the electrons and positrons are dark matter annihilation or decay products is also consistent. Fortunately, the Fermi-LAT diffuse gamma ray measurements can further test these models, since the electrons and positrons produce gamma rays in their interactions in the interstellar medium. Although the dark matter gamma ray signal consistent with the local electron and positron measurements should be quite large, as we review, there are substantial uncertainties in the modeling of diffuse backgrounds and, additionally, experimental uncertainties that make it difficult to claim a dark matter discovery. In this paper, we introduce an alternative method for understanding the diffuse gamma ray spectrum in which we take the intensity ratio in each energy bin of two different regions of the sky, thereby canceling common systematic uncertainties. For many spectra, this ratio fits well to a power law with a single break in energy. The two measured exponent indices are a robust discriminant between candidate models, and we demonstrate that dark matter annihilation scenarios can predict index values that require "extreme" parameters for background-only explanations.Comment: v1: 11 pages, 7 figures, 1 table, revtex4; v2: 13 pages, 8 figures, 1 table, revtex4, Figure 4 added, minor additions made to text, references added, conclusions unchanged, published versio

Population genomics of mycobacterium ieprae reveals a new genotype in Madagascar and the Comoros

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, Mycobacterium leprae. In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the M. leprae strains circulating in Madagascar (n = 30) and the Comoros (n = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most M. leprae strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.Immunogenetics and cellular immunology of bacterial infectious disease

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation