Transmission, distribution and drug resistance-conferring mutations of extensively drug-resistant tuberculosis in the Western Cape Province, South Africa

Extensively drug-resistant tuberculosis (XDR-TB), defined as resistance to at least isoniazid (INH), rifampicin (RIF), a fluoroqui-nolone (FQ) and a second-line injectable drug (SLID), is difficult to treat and poses a major threat to TB control. The transmission dynamics and distribution of XDR Mycobacterium tuberculosis (Mtb) strains have not been thoroughly investigated. Using whole genome sequencing data on 461 XDR-Mtb strains, we aimed to investigate the geographical distribution of XDR-Mtb strains in the Western Cape Province of South Africa over a 10 year period (2006-2017) and assess the association between Mtb sub-lineage, age, gender, geographical patient location and membership or size of XDR-TB clusters. First, we identified transmission clusters by excluding drug resistance-conferring mutations and using the 5 SNP cutoff, followed by merging clusters based on their most recent common ancestor. We then consecutively included variants conferring resistance to INH, RIF, ethambutol (EMB), pyrazinamide (PZA), SLIDs and FQs in the cluster definition. Cluster sizes were classified as small (2-4 isolates), medium (5-20 isolates), large (21-100 isolates) or very large (>100 isolates) to reflect the success of individual strains. We found that most XDR-TB strains were clustered and that including variants conferring resistance to INH, RIF, EMB, PZA and SLIDs in the cluster definition did not significantly reduce the proportion of clustered isolates (85.5-82.2 %) but increased the number of patients belonging to small clusters (4.3-12.4 %, P=0.56). Inclusion of FQ resistance-conferring variants had the greatest effect, with 11 clustered isolates reclassified as unique while the number of clusters increased from 17 to 37. Lineage 2 strains (lineage 2.2.1 typical Beijing or lineage 2.2.2 atypical Beijing) showed the large clusters which were spread across all health districts of the Western Cape Province. We identified a significant association between residence in the Cape Town metropole and cluster membership (P=0.016) but no association between gender, age and cluster membership or cluster size (P=0.39). Our data suggest that the XDR-TB epidemic in South Africa probably has its origin in the endemic spread of MDR Mtb and pre-XDR Mtb strains followed by acquisition of FQ resistance, with more limited transmission of XDR Mtb strains. This only became apparent with the inclusion of drug resistance-conferring variants in the definition of a cluster. In addition to the prevention of amplification of resistance, rapid diagnosis of MDR, pre-XDR and XDR-TB and timely initiation of appropriate treatment is needed to reduce transmission of difficult-to-treat TB

Models of HoTT and the Constructive View of Theories

Homotopy Type theory and its Model theory provide a novel formal semantic framework for representing scientific theories. This framework supports a constructive view of theories according to which a theory is essentially characterised by its methods. The constructive view of theories was earlier defended by Ernest Nagel and a number of other philosophers of the past but available logical means did not allow these people to build formal representational frameworks that implement this view

UV and optical light transmission properties in deep ice at the South Pole

Both absorption and scattering of light at wavelengths 410 to 610 nanometers were measured in the South Pole ice at depths 0.8 to 1 kilometer with the laser calibration system of the Antarctic Muon And Neutrino Detector Array (AMANDA). At the shortest wavelengths the absorption lengths exceeded 200 meters—an order of magnitude longer than has been reported for laboratory ice. The absorption shows a strong wavelength dependence while the scattering length is found to be independent of the wavelength, consistent with the hypothesis of a residual density of air bubbles in the ice. The observed linear decrease of the inverse scattering length with depth is compatible with an earlier measurement by the AMANDA collaboration (at ∼515 nanometers)

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Nuclear reactions in the storage ring ESR with EXL

The EXL project aims to study nuclear structure by direct reactions in inverse kinematics at the storage rings of the future FAIR facility. In this contribution, we present the status of the project: the technical implementation at the ESR at GSI and preliminary results of the EXL campaign in 2012, the first using also a radioactive beam

General Synthetic Domain Theory - A Logical Approach

Synthetic Domain Theory (SDT) is a version of Domain Theory where "all functions are continuous". In [14, 12] there has been developed a logical and axiomatic version of SDT which is special in the sense that it captures the essence of Domain Theory `a la Scott but rules out other important notions of domain. In this article we will give a logical and axiomatic account of General Synthetic Domain Theory (GSDT) aiming to grasp the structure common to all notions of domain as advocated by various authors. As in [14, 12] the underlying logic is a sufficiently expressive version of constructive type theory. We start with a few basic axioms giving rise to a core theory on top of which we study various notions of predomains as well-complete and replete S-spaces [9], define the appropriate notion of domain and verify the usual induction principles.

Coreflections in Algebraic Quantum Logic

Contains fulltext : 93798.pdf (preprint version ) (Open Access) Contains fulltext : 93798.pdf (publisher's version ) (Open Access

Work function homogeneity of monolayer passivated ITO surfaces for organic solar cells

The ITO transparent electrode surface is passivated either by organic quinoline molecules or by ions of periodic and phosphoric acids for organic solar cells. Passivated surfaces are investigated by means of Kelvin probe force microscop