Repeated bronchoscopy in health and obstructive lung disease: is the airway microbiome stable?

Objective Little is known concerning the stability of the lower airway microbiome. We have compared the microbiota identified by repeated bronchoscopy in healthy subjects and patients with ostructive lung diseaseases (OLD). Methods 21 healthy controls and 41 patients with OLD completed two bronchoscopies. In addition to negative controls (NCS) and oral wash (OW) samples, we gathered protected bronchoalveolar lavage in two fractions (PBAL1 and PBAL2) and protected specimen brushes (PSB). After DNA extraction, we amplified the V3V4 region of the 16S rRNA gene, and performed paired-end sequencing (Illumina MiSeq). Initial bioinformatic processing was carried out in the QIIME-2 pipeline, identifying amplicon sequence variants (ASVs) with the DADA2 algorithm. Potentially contaminating ASVs were identified and removed using the decontam package in R and the sequenced NCS. Results A final table of 551 ASVs consisted of 19 × 106 sequences. Alpha diversity was lower in the second exam for OW samples, and borderline lower for PBAL1, with larger differences in subjects not having received intercurrent antibiotics. Permutational tests of beta diversity indicated that within-individual changes were significantly lower than between-individual changes. A non-parametric trend test showed that differences in composition between the two exams (beta diversity) were largest in the PSBs, and that these differences followed a pattern of PSB > PBAL2 > PBAL1 > OW. Time between procedures was not associated with increased diversity. Conclusion The airways microbiota varied between examinations. However, there is compositional microbiota stability within a person, beyond that of chance, supporting the notion of a transient airways microbiota with a possibly more stable individual core microbiome.publishedVersio

Investigating the Day-to-Day Experiences of Users with Traumatic Brain Injury with Conversational Agents

Traumatic brain injury (TBI) can cause cognitive, communication, and psychological challenges that profoundly limit independence in everyday life. Conversational Agents (CAs) can provide individuals with TBI with cognitive and communication support, although little is known about how they make use of CAs to address injury-related needs. In this study, we gave nine adults with TBI an at-home CA for four weeks to investigate use patterns, challenges, and design requirements, focusing particularly on injury-related use. The findings revealed significant gaps between the current capabilities of CAs and accessibility challenges faced by TBI users. We also identified 14 TBI-related activities that participants engaged in with CAs. We categorized those activities into four groups: mental health, cognitive activities, healthcare and rehabilitation, and routine activities. Design implications focus on accessibility improvements and functional designs of CAs that can better support the day-to-day needs of people with TBI.Comment: In Proceedings The 25th International ACM SIGACCESS Conference on Computers and Accessibility (ASSETS'23

SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.</jats:p

Protected sampling is preferable in bronchoscopic studies of the airway microbiome

The aim was to evaluate susceptibility of oropharyngeal contamination with various bronchoscopic sampling techniques. 67 patients with obstructive lung disease and 58 control subjects underwent bronchoscopy with small-volume lavage (SVL) through the working channel, protected bronchoalveolar lavage (PBAL) and bilateral protected specimen brush (PSB) sampling. Subjects also provided an oral wash (OW) sample, and negative control samples were gathered for each bronchoscopy procedure. DNA encoding bacterial 16S ribosomal RNA was sequenced and bioinformatically processed to cluster into operational taxonomic units (OTU), assign taxonomy and obtain measures of diversity. The proportion of Proteobacteria increased, whereas Firmicutes diminished in the order OW, SVL, PBAL, PSB (p<0.01). The alpha-diversity decreased in the same order (p<0.01). Also, beta-diversity varied by sampling method (p<0.01), and visualisation of principal coordinates analyses indicated that differences in diversity were smaller between OW and SVL and OW and PBAL samples than for OW and the PSB samples. The order of sampling (left versus right first) did not influence alpha- or beta-diversity for PSB samples. Studies of the airway microbiota need to address the potential for oropharyngeal contamination, and protected sampling might represent an acceptable measure to minimise this problem.publishedVersio

A Two-stage Flow-based Intrusion Detection Model ForNext-generation Networks

The next-generation network provides state-of-the-art access-independent services over converged mobile and fixed networks. Security in the converged network environment is a major challenge. Traditional packet and protocol-based intrusion detection techniques cannot be used in next-generation networks due to slow throughput, low accuracy and their inability to inspect encrypted payload. An alternative solution for protection of next-generation networks is to use network flow records for detection of malicious activity in the network traffic. The network flow records are independent of access networks and user applications. In this paper, we propose a two-stage flow-based intrusion detection system for next-generation networks. The first stage uses an enhanced unsupervised one-class support vector machine which separates malicious flows from normal network traffic. The second stage uses a self-organizing map which automatically groups malicious flows into different alert clusters. We validated the proposed approach on two flow-based datasets and obtained promising results

Unconstrained Optimization and Calibration of a Kinematic-Cyclic Plasticity Model

In this paper, a mixed kinematic and isotropic cyclic plasticity model based on the concept of Fuzzy Set Plasticity, which is a versatile technique for modeling a range of complex phenomena observed in non-proportional loading in soil-structure interaction, is implemented. It is followed by a discussion of associated model parameters and model parameter sensitivity analysis. The use of zero-order numerical optimization techniques is discussed and its application in calibrating the Fuzzy Set Plasticity Model is presented. The performance and comparison among these numerical optimization schemes are also examined and discussed

Speaker-Independent Isolated Word Recognition Using Multiple Hidden Markov Models

A multi-HMM speaker-independent isolated word recognition system is described. In this system, three vector quantization methods, the LBG algorithm, the EM algorithm, and a new MGC algorithm, are used for the classification of the speech space. These quantizations of the speech space are then used to produce three HMMs for each word in the vocabulary. In the recognition step, the Viterbi algorithm is used in the three sub-recognizers. The log probabilities of the observation sequences matching the models are multiplied by the weights determined by the recognition accuracies of individual sub-recognizers and summed to give the log probability that the utterance is of a particular word in the vocabulary. This multi-HMM system results in a reduction of about 50 per cent in the error rate in comparison with the single model system. INTRODUCTION Currently, one of the most popular approaches to speech recognition is the combination of Vector Quantization (VQ) for the encoding of segments o..