A Machine Learning-Based Raman Spectroscopic Assay for the Identification of Burkholderia mallei and Related Species

Burkholderia (B.) mallei, the causative agent of glanders, and B. pseudomallei, the causative agent of melioidosis in humans and animals, are genetically closely related. The high infectious potential of both organisms, their serological cross-reactivity, and similar clinical symptoms in human and animals make the differentiation from each other and other Burkholderia species challenging. The increased resistance against many antibiotics implies the need for fast and robust identification methods. The use of Raman microspectroscopy in microbial diagnostic has the potential for rapid and reliable identification. Single bacterial cells are directly probed and a broad range of phenotypic information is recorded, which is subsequently analyzed by machine learning methods. Burkholderia were handled under biosafety level 1 (BSL 1) conditions after heat inactivation. The clusters of the spectral phenotypes and the diagnostic relevance of the Burkholderia spp. were considered for an advanced hierarchical machine learning approach. The strain panel for training involved 12 B. mallei, 13 B. pseudomallei and 11 other Burkholderia spp. type strains. The combination of top- and sub-level classifier identified the mallei-complex with high sensitivities (>95%). The reliable identification of unknown B. mallei and B. pseudomallei strains highlighted the robustness of the machine learning-based Raman spectroscopic assay

Discrimination of Vaccinated and infected Pigs by Salmonella-specific IGa antibodies

Isotype switching from IgM to IgG or IgA leads to generation of high affinity antibodies during the immune response. This phenomenon can be applied for differentiation of early and late infection stages. The purpose of this study was to evaluate the applicability of a newly developed Ig-isotype specific Salmonella antibody ELISA for discrimination between vaccinated and infected pigs. Using this novel ELISA we were able to detect different patterns of Salmonella-specific IgM, IgG and IgA antibodies following immunization with a S. Typhimurium live vaccine or after experimental infection with a nalidixic-acid resistant wild-type strain of S. Typhimurium. Interestingly, Salmonella-specific IgA antibodies represented an excellent tool for the recognition of fresh infection in vaccinated pigs. Under SPF conditions, we were able to discriminate between naive, vaccinated, experimentally infected nonvaccinated, and experimentally infected vaccinated animals. However, the highest specific IgA levels were detected in challenged vaccinated pigs. Preliminary results from field trials support the findings from experiments using SPF animals

P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage

Stakeholder mapping to support invasive non-native species management in South America

Peer reviewe

Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm{NN}}} = 2.76 TeV

The inclusive transverse momentum ($p_{\rm T}$) distributions of primary charged particles are measured in the pseudo-rapidity range $|\eta|<0.8$ as a function of event centrality in Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}=2.76$ TeV with ALICE at the LHC. The data are presented in the $p_{\rm T}$ range $0.15<p_{\rm T}<50$ GeV/$c$ for nine centrality intervals from 70-80% to 0-5%. The Pb-Pb spectra are presented in terms of the nuclear modification factor $R_{\rm{AA}}$ using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-$p_{\rm T}$ particles strongly depends on event centrality. In central collisions (0-5%) the yield is most suppressed with $R_{\rm{AA}}\approx0.13$ at $p_{\rm T}=6$-7 GeV/$c$. Above $p_{\rm T}=7$ GeV/$c$, there is a significant rise in the nuclear modification factor, which reaches $R_{\rm{AA}} \approx0.4$ for $p_{\rm T}>30$ GeV/$c$. In peripheral collisions (70-80%), the suppression is weaker with $R_{\rm{AA}} \approx 0.7$ almost independently of $p_{\rm T}$. The measured nuclear modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/284

Collimation for the LHC high intensity beams

The unprecedented design intensities of the LHC require several important advances in beam collimation. With its more than 100 collimators, acting on various planes and beams, the LHC collimation system is the biggest and most performing such system ever designed and constructed. The solution for LHC collimation is explained, the technical components are introduced and the initial performance is presented. Residual beam leakage from the system is analysed. Measurements and simulations are presented which show that collimation efficiencies of better than 99.97 % have been measured with the 3.5 TeV proton beams of the LHC, in excellent agreement with expectations.peer-reviewe

Discrimination of Vaccinated and infected Pigs by Salmonella-specific IGa antibodies

Isotype switching from IgM to IgG or IgA leads to generation of high affinity antibodies during the immune response. This phenomenon can be applied for differentiation of early and late infection stages. The purpose of this study was to evaluate the applicability of a newly developed Ig-isotype specific Salmonella antibody ELISA for discrimination between vaccinated and infected pigs. Using this novel ELISA we were able to detect different patterns of Salmonella-specific IgM, IgG and IgA antibodies following immunization with a S. Typhimurium live vaccine or after experimental infection with a nalidixic-acid resistant wild-type strain of S. Typhimurium. Interestingly, Salmonella-specific IgA antibodies represented an excellent tool for the recognition of fresh infection in vaccinated pigs. Under SPF conditions, we were able to discriminate between naive, vaccinated, experimentally infected nonvaccinated, and experimentally infected vaccinated animals. However, the highest specific IgA levels were detected in challenged vaccinated pigs. Preliminary results from field trials support the findings from experiments using SPF animals.</p