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The design spectrum has been determined for two of the 15 graphs with six vertices and ten edges. In this paper we completely solve the design spectrum problem for a further eight of these graphs.

Evidence suggests that the gut microbiome may play a role in multiple sclerosis (MS). However, the majority of the studies have focused on gut bacterial communities; none have examined the fungal microbiota (mycobiota) in persons with pediatric-onset multiple sclerosis (POMS). We examined the gut mycobiota in persons with and without POMS through a cross-sectional examination of the gut mycobiota from 46 participants’ stool samples (three groups: 18 POMS, 13 acquired monophasic demyelinating syndromes [monoADS], and 15 unaffected controls). Using metataxonomic sequencing of the fungal internal transcribed spacer region 2, the fungal profiles were compared between participants using visualizations, statistical tests, and predictive analysis. While the mycobiome α- (Shannon and inverse Simpson indices) and β-diversity differed across the three groups [analysis of variance (ANOVA), p

Abstract Background Helicobacter pylori infection is prevalent worldwide and can lead to peptic ulcer disease (PUD) and gastric cancer. Effective diagnosis and treatment of H. pylori infection by gastroenterologists and family physicians is crucial. However, there are differing views on optimal diagnosis and treatment. The objective of this study is to understand the impressions of Canadian physicians regarding H. pylori diagnosis and treatment and whether impressions differ between gastroenterologists and family physicians. A second objective is to understand physician perspectives on rising antibiotic resistance and how that guides empiric management. Methods A survey facilitated via REDCap was administered to Canadian gastroenterologists and family physicians. A total of 105 participants completed the survey, including 43 gastroenterologists and 62 family physicians. Gastroenterologists were recruited from across the country and family physicians were recruited from Manitoba. Results For diagnosis of H. pylori, 67% of gastroenterologists reported endoscopic biopsies for histology assessment as most common and 73% of family physicians reported serology as their main diagnostic test. While nearly all gastroenterologists believed antibiotic resistance to be a problem, nearly one quarter of family physicians did not believe it was a problem. Conclusions There is variability in practices among both gastroenterologists and family physicians regarding diagnosis of H. pylori infection. There was consensus that local antibiotic resistance patterns should guide management. If known, the degree and patterns of antibiotic resistance could bring a more uniform consensus to H. pylori management. Greater education of physicians, especially family physicians regarding management of H pylori is needed.

Background The first cases of the COVID-19 pandemic in Australia were recorded in January 2020, which was during the ‘Black Summer’ bushfires of 2019–20 and prior to additional disasters in some regions. Few studies have considered the compound impact of disasters and the pandemic. Aims To improve understanding of the impact on mental health and well-being of the pandemic in disaster-affected communities. Method We conducted semi-structured interviews (n = 18) with community members and online focus groups (n = 31) with help providers from three regions of rural Australia affected by bushfires and the pandemic. Results Six themes were produced: (a) ‘Pulling together, pulling apart’, describing experiences after bushfires and prior to impacts of the pandemic; (b) ‘Disruption of the ‘normal response’, encompassing changes to post-disaster recovery processes attributed to the pandemic; (c) ‘Escalating tensions and division in the community’, describing impacts on relationships; (d) ‘Everywhere you turn you get a slap in the face’, acknowledging impacts of bureaucratic ‘red tape’; (e) ‘There are layers of trauma’, highlighting intersecting traumas and pre-existing vulnerabilities; and (f) ‘Where does the help come from when we can't do it?’, encompassing difficulties accessing services and impacts on the helping workforce. Conclusions This study furthers our understanding of compound disasters and situates pandemic impacts in relation to processes of adjustment and recovery from bushfires. It highlights the need for long-term approaches to resilience and recovery, investment in social infrastructure, multi-component approaches to workforce issues, and strategies to increase mental health support and pathways across services.

Abstract Objective To examine the gut microbiota in individuals with and without pediatric‐onset multiple sclerosis (MS). Methods We compared stool‐derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease‐modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset 0.1), taxa‐level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6–11.2, p = 0.004, Q = 0.01), and lower abundances of short‐chain fatty acid (SCFA)‐producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q eightfold higher abundance for Candidatus Stoquefichus and Tyzzerella (aRR = 8.8–12.8, p

ABSTRACT The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possessed by three variants of concern (VOCs), B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the coronavirus disease 2019 (COVID-19) pandemic. We developed and validated a single nucleotide polymorphism real-time reverse transcription PCR assay using allelic discrimination of the spike gene N501Y mutation to screen for potential variants of concern and differentiate them from SARS-CoV-2 lineages without the N501Y mutation. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or N501 wild type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real-time reverse transcriptase PCR assay. Our assay, compared to Sanger sequencing for single nucleotide polymorphism detection, demonstrated positive percent agreement of 100% for all 57 specimens displaying the N501Y mutation, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wild type and mutant. Negative percent agreement was 100% in all 103 specimens typed as N501 wild type, with A23063 identified as wild type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole-genome sequencing, which are time consuming, labor intensive, and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole-genome sequencing. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, several variants of concern (VOCs) have been detected, for example, B.1.1.7, B.1.351, P.1, and B.1.617.2. The VOCs pose a threat to public health efforts to control the spread of the virus. As such, surveillance and monitoring of these VOCs is of the utmost importance. Our real-time RT-PCR assay helps with surveillance by providing an easy method to quickly survey SARS-CoV-2 specimens for VOCs carrying the N501Y single nucleotide polymorphism (SNP). Samples that test positive for the N501Y mutation in the spike gene with our assay can be sequenced to identify the lineage. Thus, our assay helps to focus surveillance efforts and decrease turnaround times.

Chronic intestinal inflammation and microbial dysbiosis are hallmarks of colorectal cancer (CRC) and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. However, the mechanistic relationship between gut dysbiosis and disease has not yet been fully characterized. Although the “trigger” of intestinal inflammation remains unknown, a wealth of evidence supports the role of the gut microbiome as a mutualistic pseudo-organ that significantly influences intestinal homeostasis and is capable of regulating host immunity. In recent years, culture-independent methods for assessing microbial communities as a whole (termed meta-omics) have grown beyond taxonomic identification and genome characterization (metagenomics) into new fields of research that collectively expand our knowledge of microbiomes. Metatranscriptomics, metaproteomics, and metabolomics are meta-omics techniques that aim to describe and quantify the functional activity of the gut microbiome. Uncovering microbial metabolic contributions in the context of IBD and CRC using these approaches provides insight into how the metabolic microenvironment of the GI tract shapes microbial community structure and how the microbiome, in turn, influences the surrounding ecosystem. Immunological studies in germ-free and wild-type mice have described several host-microbiome interactions that may play a role in autoinflammation. Chronic colitis is a precursor to CRC, and changes in the gut microbiome may be an important link triggering the neoplastic process in chronic colitis. In this review, we describe several microbiome-mediated mechanisms of host immune signaling, such as short-chain fatty acid (SCFA) and bile acid metabolism, inflammasome activation, and cytokine regulation in the context of IBD and CRC, and discuss the supporting role for these mechanisms by meta-omics data.

BackgroundIn studies evaluating the microbiome, numerous factors can contribute to technical variability. These factors include DNA extraction methodology, sequencing protocols, and data analysis strategies. We sought to evaluate the impact these factors have on the results obtained when the sequence data are independently generated and analyzed by different laboratories.MethodsTo evaluate the effect of technical variability, we used human intestinal biopsy samples resected from individuals diagnosed with an inflammatory bowel disease (IBD), including Crohn’s disease (n = 12) and ulcerative colitis (n = 10), and those without IBD (n = 10). Matched samples from each participant were sent to three laboratories and studied using independent protocols for DNA extraction, library preparation, targeted-amplicon sequencing of a 16S rRNA gene hypervariable region, and processing of sequence data. We looked at two measures of interest – Bray–Curtis PERMANOVA R2 values and log2 fold-change estimates of the 25 most-abundant taxa – to assess variation in the results produced by each laboratory, as well the relative contribution to variation from the different extraction, sequencing, and analysis steps used to generate these measures.ResultsThe R2 values and estimated differential abundance associated with diagnosis were consistent across datasets that used different DNA extraction and sequencing protocols, and within datasets that pooled samples from multiple protocols; however, variability in bioinformatic processing of sequence data led to changes in R2 values and inconsistencies in taxonomic assignment and abundance estimates.ConclusionAlthough the contribution of DNA extraction and sequencing methods to variability were observable, we find that results can be robust to the various extraction and sequencing approaches used in our study. Differences in data processing methods have a larger impact on results, making comparison among studies less reliable and the combined analysis of bioinformatically processed samples nearly impossible. Our results highlight the importance of making raw sequence data available to facilitate combined and comparative analyses of published studies using common data processing protocols. Study methodologies should provide detailed data processing methods for validation, interpretability, reproducibility, and comparability.

Clinical metagenomics (CMg) is the discipline that refers to the sequencing of all nucleic acid material present within a clinical specimen with the intent to recover clinically relevant microbial information. From a diagnostic perspective, next-generation sequencing (NGS) offers the ability to rapidly identify putative pathogens and predict their antimicrobial resistance profiles to optimize targeted treatment regimens. Since the introduction of metagenomics nearly a decade ago, numerous reports have described successful applications in an increasing variety of biological specimens, such as respiratory secretions, cerebrospinal fluid, stool, blood and tissue. Considerable advancements in sequencing and computational technologies in recent years have made CMg a promising tool in clinical microbiology laboratories. Moreover, costs per sample and turnaround time from specimen receipt to clinical management continue to decrease, making the prospect of CMg more feasible. Many difficulties, however, are associated with CMg and warrant further improvements such as the informatics infrastructure and analytical pipelines. Thus, the current review focuses on comprehensively assessing applications of CMg for diagnostic and subtyping purposes. Keywords: Clinical metagenomics, Diagnosis, Clinical microbiology laboratory, Pathogen detection, Culture-independent diagnostic test, Next-generation sequencing

The human microbiome has received decades of attention from scientific and medical research communities. The human gastrointestinal tract is host to immense populations of microorganisms including bacteria, viruses, archaea, and fungi (the gut microbiota). High-throughput sequencing and computational advancements provide unprecedented ability to investigate the structure and function of microbial communities associated with the human body in health and disease. Most research to date has largely focused on elucidating the bacterial component of the human gut microbiota. Study of the gut “mycobiota,” which refers to the diverse array of fungal species, is a relatively new and rapidly progressing field. Though omnipresent, the number and abundance of fungi occupying the human gut is orders of magnitude smaller than that of bacteria. Recent insights however, have suggested that the gut mycobiota may be intricately linked to health and disease. Evaluation of the gut mycobiota has shown that not only are the fungal communities altered in disease, but they also play a role in maintaining intestinal homeostasis and influencing systemic immunity. In addition, it is now widely accepted that host-fungi and bacteria-fungi associations are critical to host health. While research of the gut mycobiota in health and disease is on the rise, little research has been performed in the context of neuroimmune and neurodegenerative conditions. Gut microbiota dysbiosis (specifically bacteria and archaea) have been reported in neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's, among others. Given the widely accepted bacteria-fungi associations and paucity of mycobiota-specific studies in neurological disease, this review discusses the potential role fungi may play in multiple sclerosis and other neurological diseases. Herein, we provide an overview of recent advances in gut mycobiome research and discuss the plausible role of both intestinal and non-intestinal fungi in the context of neuroimmune and neurodegenerative conditions.

This research was designed to evaluate the extent to which power functions can predict performance on a task when performance context has been altered. Since power functions reliably describe performance improvements during practice, an assumption implicit in some theories of skill acquisition and transfer is that transfer performance will continue to improve as an extrapolation of the practice power function. In the training phase of Experiment 1, 120 participants practiced solving simple problems from the six-times table. In the transfer phase, these same problems were presented again, intermixed with problems from one of the six conditions differing in various respects to the target problems. With the exception of two of these six conditions, performance on the target problems was slower than was predicted by training phase power function extrapolations. Where the nature of the task was altered, this disruption only occurred in the initial stages of transfer, with performance returning quickly to predicted levels. Where an increased scope of knowledge was required to perform the task, the disruption was more prolonged. Experiment 2 demonstrated that a spacing effect explanation of the results of Experiment 1 was not valid. Results were interpreted as reflecting the effect a change in the conceptual context of a task has on transfer performance. These findings have implications for theories of skill acquisition and transfer that assume transfer performance of established skills will continue to improve according to an extrapolation of the practice power function regardless of the conceptual context of the task.