High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography

Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

Utilisation of measurements to predict the relationship between contact forces on the pipe conveyor idler rollers and the tension force of the conveyor belt

Operating conditions of rubber-textile conveyor belts represent a source of information providing a wide spectrum of operating characteristics. Various theoretical and experimental methods, mostly based on ex post approach, have been recently employed for the identification of such operating characteristics. However, this approach is not very effective and is used as a source of data for various follow-up analyses. On the other hand, the operation of conveyors requires the prediction of needed forces and adjustments of operation based on such forces. This is called ex ante approach. The paper covers an introduction of the option allowing operating characteristics to be predicted based on a tool basis determined by experimental measurements. The whole procedure is demonstrated by a specific example focusing on the prediction of the contact force – tension force relationship. The presented results have been derived using the tools of statistical analysis. The article presents only the first part of the research in which data was recorded without the material being transported, there are two reasons for this: 1. Finding information about the behaviour of the conveyor belt when it has been implemented and started without the material being transported, 2. Detection of changes occurring in the conveyor belt when burdening it with conveyed material. © 2019 Elsevier Ltd[VEGA 1/0403/18]; [VEGA 1/0045/18]; [VEGA 1/0063/16]; [KEGA 012TUKE-4/2019]; [KEGA 013TUKE-4/2019

Scientific Reports / Comparison of a personalized breast dosimetry method with standard dosimetry protocols

Average glandular dose (AGD) in digital mammography crucially depends on the estimation of breast glandularity. In this study we compared three different methods of estimating glandularities according to Wu, Dance and Volpara with respect to resulting AGDs. Exposure data from 3050 patient images, acquired with a GE Senographe Essential constituted the study population of this work. We compared AGD (1) according to Dance et al. applying custom g, c, and s factors using HVL, breast thickness, patient age and incident air kerma (IAK) from the DICOM headers; (2) according to Wu et al. as determined by the GE system; and (3) AGD derived with the Dance model with personalized c factors using glandularity determined with the Volpara (Volpara Solutions, Wellington, New Zealand) software (Volpare AGD). The ratios of the resulting AGDs were analysed versus parameters influencing dose. The highest deviation between the resulting AGDs was found in the ratio of GE AGD to Volpara AGD for breast thicknesses between 20 and 40 mm (ratio: 0.80). For thicker breasts this ratio is close to one (1 0.02 for breast thicknesses >60 mm). The Dance to Volpara ratio was between 0.86 (breast thickness 2040 mm) and 0.99 (>80 mm), and Dance/GE AGD was between 1.07 (breast thickness 2040 mm) and 0.98 (4160, and >80 mm). Glandularities by Volpara were generally smaller than the one calculated with the Dance method. This effect is most pronounced for small breast thickness and older ages. Taking the considerable divergences between the AGDs from different methods into account, the selection of the method should by done carefully. As the Volpara method provides an analysis of the individual breast tissue, while the Wu and the Dance methods use look up tables and custom parameter sets, the Volpara method might be more appropriate if individual ADG values are sought. For regulatory purposes and comparison with diagnostic reference values, the method to be used needs to be defined exactly and clearly be stated. However, it should be accepted that dose values calculated with standardized models, like AGD and also effective dose, are afflicted with a considerable uncertainty budgets that need to be accounted for in the interpretation of these values.(VLID)493237

The Reference Building Process with special respect to sustainable certification and the mandatory BIM requirements management

Recently, research on 5D processes has brought innovation into the construction sector. However, one still feels a lack of clarity in this sector. Although BIM research has been carried out in many countries, very few standard building processes have been clearly identified. The RIBA Plan of Works in the UK, and the HOAI in Germany can be used to support the designer for the description of the services expected from them. Whereas the new RIBA Plan of Works 2013 [15] already includes some support, in case of the HOAI building owners can still hardly find guidance about the contracted design processes and how BIM processes are to be aligned with the overall process structure. Information exchanges are not defined and there is a big uncertainty about how to implement BIM in construction projects. To rectify this, the Reference Building Process Map is proposed including all relevant processes in the design and construction phases for the main stakeholders (owner, architect, technical experts, constructing company, public authority and consultants). In particular, the BIM Manager role is added with its interaction with the other stakeholders. Based on this process map, the steps which are mandatory for the sustainable certification process are also identified. The advantages of using BIM for the certification process are clearly pointed out. In its advanced form, each major process is described by the BIM data requirements to be carried out efficiently. The BIM data requirement management identifies the data needs with regard to the Level of Detail (geometry) and Information (property content). It also addresses the responsible role for delivering and validating BIM data, and enables automatic checking procedures to guarantee the right BIM quality for the BIM processes

Automated tube voltage selection in pediatric non-contrast chest CT.

BACKGROUND:Modern CT scanners provide automatic dose adjustment systems, which are promising options for reducing radiation dose in pediatric CT scans. Their impact on patient dose, however, has not been investigated sufficiently thus far. OBJECTIVE:To evaluate automated tube voltage selection (ATVS) in combination with automated tube current modulation (ATCM) in non-contrast pediatric chest CT, with regard to the diagnostic image quality. MATERIALS AND METHODS:There were 160 non-contrast pediatric chest CT scans (8.7±5.4 years) analyzed retrospectively without and with ATVS. Correlations of volume CT Dose Index (CTDIvol) and effective diameter, with and without ATVS, were compared using Fisher's z-transformation. Image quality was assessed by mean signal-difference-to-noise ratios (SDNR) in the aorta and in the left main bronchus using the independent samples t-test. Two pediatric radiologists and a general radiologist rated overall subjective Image quality. Readers' agreement was assessed using weighted kappa coefficients. A p value <0.05 was considered significant. RESULTS:CTDIvol correlation with the effective diameter was r = 0.62 without and r = 0.80 with ATVS (CI: -0.04 to -0.60; p = 0.025). Mean SDNR was 10.88 without and 10.03 with ATVS (p = 0.0089). Readers' agreement improved with ATVS (weighted kappa between pediatric radiologists from 0.1 (0.03-0.16) to 0.27 (0.09-0.45) with ATVS; between general and each pediatric radiologist from 0.1 (0.06-0.14) to 0.12 (0.05-0.20), and from 0.22 (0.11-0.34) to 0.36 (0.24-0.49)). CONCLUSION:ATVS, combined with ATCM, results in a radiation dose reduction for pediatric non-contrast chest CT without a loss of diagnostic image quality and prevents errors in manual tube voltage setting, and thus protecting larger children against an unnecessarily high radiation exposure

Dose modulated retrospective ECG-gated versus non-gated 64-row CT angiography of the aorta at the same radiation dose: Comparison of motion artifacts, diagnostic confidence and signal-to-noise-ratios

To compare ECG-gated and non-gated CT angiography of the aorta at the same radiation dose, with regard to motion artifacts (MA), diagnostic confidence (DC) and signal-to-noise-ratios (SNRs)