Improving the spatial and statistical accuracy in X-ray Raman scattering based direct tomography

An algorithm to simultaneously increase the spatial and statistical accuracy of X-ray Raman scattering (XRS) based tomographic images is presented. Tomography that utilizes XRS spectroscopy signals as a contrast for the images is a new and promising tool for investigating local atomic structure and chemistry in heterogeneous samples. The algorithm enables the spatial resolution to be increased based on a deconvolution of the optical response function of the spectrometer and, most importantly, it allows for the combination of data collected from multiple analyzers and thus enhances the statistical accuracy of the measured images.Peer reviewe

Random forest machine learning method outperforms prehospital National Early Warning Score for predicting one-day mortality : A retrospective study

Aim of the study: The National Early Warning Score (NEWS) is a validated method for predicting clinical deterioration in hospital wards, but its performance in prehospital settings remains controversial. Modern machine learning models may outperform traditional statistical analyses for predicting short-term mortality. Thus, we aimed to compare the mortality prediction accuracy of NEWS and random forest machine learning using prehospital vital signs. Methods: In this retrospective study, all electronic ambulance mission reports between 2008 and 2015 in a single EMS system were collected. Adult patients (>= 18 years) were included in the analysis. Random forest models with and without blood glucose were compared to the traditional NEWS for predicting one-day mortality. A ten-fold cross-validation method was applied to train and validate the random forest models. Results: A total of 26,458 patients were included in the study of whom 278 (1.0%) died within one day of ambulance mission. The area under the receiver operating characteristic curve for one-day mortality was 0.836 (95% CI, 0.810-0.860) for NEWS, 0.858 (95% CI, 0.832-0.883) for a random forest trained with NEWS variables only and 0.868 (0.843-0.892) for a random forest trained with NEWS variables and blood glucose. Conclusion: A random forest algorithm trained with NEWS variables was superior to traditional NEWS for predicting one-day mortality in adult prehospital patients, although the risk of selection bias must be acknowledged. The inclusion of blood glucose in the model further improved its predictive performance.Peer reviewe

Impaired osteoclast homeostasis in the cystatin B-deficient mouse model of progressive myoclonus epilepsy

Peer reviewe

Description of klebsiella spallanzanii sp. Nov. and of klebsiella pasteurii sp. nov

Klebsiella oxytoca causes opportunistic human infections and post-antibiotic haemorrhagic diarrhoea. This Enterobacteriaceae species is genetically heterogeneous and is currently subdivided into seven phylogroups (Ko1 to Ko4, Ko6 to Ko8). Here we investigated the taxonomic status of phylogroups Ko3 and Ko4. Genomic sequence-based phylogenetic analyses demonstrate that Ko3 and Ko4 formed well-defined sequence clusters related to, but distinct from, Klebsiella michiganensis (Ko1), Klebsiella oxytoca (Ko2), K. huaxiensis (Ko8) and K. grimontii (Ko6). The average nucleotide identity of Ko3 and Ko4 were 90.7% with K. huaxiensis and 95.5% with K. grimontii, respectively. In addition, three strains of K. huaxiensis, a species so far described based on a single strain from a urinary tract infection patient in China, were isolated from cattle and human faeces. Biochemical and MALDI-ToF mass spectrometry analysis allowed differentiating Ko3, Ko4 and Ko8 from the other K. oxytoca species. Based on these results, we propose the names Klebsiella spallanzanii for the Ko3 phylogroup, with SPARK_775_C1T (CIP 111695T, DSM 109531T) as type strain, and Klebsiella pasteurii for Ko4, with SPARK_836_C1T (CIP 111696T, DSM 109530T) as type strain. Strains of K. spallanzanii were isolated from human urine, cow faeces and farm surfaces, while strains of K. pasteurii were found in faecal carriage from humans, cows and turtles

The first human report of mobile colistin resistance gene, mcr-1, in Finland

Colistin resistance mediated by mobile mcr-1 gene has raised concern during the last years. After steep increase in mcr-1 reports, other mcr-gene variants (mcr-2 to mcr-5) have been revealed as well. In 2016, a clinical study was conducted on asymptomatic stool carriage of extended spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae among Finnish adults. All suspected ESBL producing bacterial isolates were first tested by phenotypic ESBL-confirmation methods, and then further analyzed with whole genome sequencing to identify the resistance genes. We found one study subject carrying a colistin resistant E.coli with a transferrable mcr-1 gene. This multi-drug resistant isolate, although initially suspected to be an ESBL producer, did not carry any ESBL genes, but was proven to carry several other resistance genes by using whole genome sequencing. Sequence type was ST93. The mcr-1 gene was connected to IncX4 plasmid which suggests that the colistin resistance gene locates in the respective plasmid. Here, we report the finding of a mcr-1 harboring human E.coli isolate from Finland. Clinical antimicrobial resistance (AMR) rates are low in Finland, and mobile colistin resistance has not been reported previously. This highlights the importance of AMR surveillance also in populations with low levels of resistance

Comparative Genomics of Bordetella pertussis Reveals Progressive Gene Loss in Finnish Strains

BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations

Prevalence and Genetic Characterization of Pertactin-Deficient Bordetella pertussis in Japan

The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn−) B. pertussis was observed in Japan. The Prn− isolate was first discovered in 1997, and 33 (27%) Prn− isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn− isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1ΔSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn− isolates, notably those harboring prn1ΔSS, significantly increased since the early 2000s, and Prn− isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn− isolates belong to MLVA-186, and 6 and 3 Prn− isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn− clinical strains (harboring prn1ΔSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn− isolates have a higher growth potential than the Prn+ back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn− strains have arisen and that Prn expression is not essential for fitness under these conditions

Comparative genomics of prevaccination and modern Bordetella pertussis strains

Contains fulltext : 89571.pdf (publisher's version ) (Open Access)BACKGROUND: Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination. RESULTS: The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains. CONCLUSIONS: Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation

Search for new physics in high-mass diphoton events from proton-proton collisions at √s = 13 TeV

Results are presented from a search for new physics in high-mass diphoton events from proton-proton collisions at sqrt(s) = 13 TeV. The data set was collected in 2016–2018 with the CMS detector at the LHC and corresponds to an integrated luminosity of 138 fb−1 . Events with a diphoton invariant mass greater than 500 GeV are considered. Two diferent techniques are used to predict the standard model backgrounds: parametric fts to the smoothly-falling background and a frst-principles calculation of the standard model diphoton spectrum at next-to-next-to-leading order in perturbative quantum chromodynamics calculations. The frst technique is sensitive to resonant excesses while the second technique can identify broad diferences in the invariant mass shape. The data are used to constrain the production of heavy Higgs bosons, Randall-Sundrum gravitons, the large extra dimensions model of Arkani-Hamed, Dimopoulos, and Dvali (ADD), and the continuum clockwork mechanism. No statistically signifcant excess is observed. The present results are the strongest limits to date on ADD extra dimensions and RS gravitons with a coupling parameter greater than 0.1