Oxygen extraction fraction (OEF) values and applications in neurological diseases.

One of the goals of this systematic review is to provide a meta-analysis-derived mean OEF of healthy volunteers. Another aim of this study is to indicate the OEF ranges of various neurological pathologies. Potential clinical applications of OEF metrics are presented. Peer-reviewed studies reporting OEF metrics derived from computed tomography (CT)/positron emission tomography (PET) and/or magnetic resonance imaging (MRI) were considered. Databases utilized included MEDLINE, PubMed, EMBASE, Web of Science, and Google Scholar. The Newcastle-Ottawa scoring system was used for evaluating studies. R Studio was utilized for the meta-analysis calculations when appropriate. The GRADE framework was utilized to assess additional findings. Of 2267 potential studies, 165 met the inclusion criteria. The healthy volunteer meta-analysis included 339 subjects and found a mean OEF value of 38.87 (37.38, 40.36), with a prediction interval of 32.40-45.34. There were no statistical differences in OEF values derived from PET versus MRI. We provided a GRADE A certainty rating for the use of OEF metrics to predict stroke occurrence in patients with symptomatic carotid or cerebral vessel disease. We provided a GRADE B certainty rating for monitoring treatment response in Moyamoya disease. Use of OEF metrics in diagnosing and/or monitoring other conditions had a GRADE C certainty rating or less. OEF might have a role in diagnosing and monitoring patients with symptomatic carotid or cerebral vessel disease and Moyamoya disease. While we found insufficient evidence to support measuring OEF metrics in other patient populations, in many cases, further studies are warranted.

Optimum quorum quenching bacteria concentration in the better-quality cell entrapping beads to control biofouling in membrane bioreactor.

Quorum quenching (QQ) by cell entrapping beads (CEBs) is known to inhibit biofouling by its biological and physical cleaning effect. Although there are better QQ media reported, due to the ease of fabrication of QQ-CEBs, this study focused on improving the quality of CEBs by comparing two distinct bead-making methods - polyvinyl alcohol-alginate (PVA-alginate) and phase inversion - and on finding the optimum concentration of QQ bacteria in the CEBs. The evaluation of PVA-alginate bead showed better uniformity, and higher mechanical and chemical strength in comparison with the phase inversion bead. Through the operations of two control membrane bioreactors (MBRs) (no bead, vacant bead) and four QQ-MBRs with different Rhodococcus sp. BH4 concentrations (2.5-15 mg cell ml-1) in PVA-alginate CEBs, the maximum QQ effect was observed by 5 mg ml-1 BH4 concentration beads. This implies that an optimum cell concentration of QQ-CEBs is crucial to economically improve MBR performance using QQ.

Molecular Aspects of the Functioning of Pathogenic Bacteria Biofilm Based on Quorum Sensing (QS) Signal-Response System and Innovative Non-Antibiotic Strategies for Their Elimination.

One of the key mechanisms enabling bacterial cells to create biofilms and regulate crucial life functions in a global and highly synchronized way is a bacterial communication system called quorum sensing (QS). QS is a bacterial cell-to-cell communication process that depends on the bacterial population density and is mediated by small signalling molecules called autoinducers (AIs). In bacteria, QS controls the biofilm formation through the global regulation of gene expression involved in the extracellular polymeric matrix (EPS) synthesis, virulence factor production, stress tolerance and metabolic adaptation. Forming biofilm is one of the crucial mechanisms of bacterial antimicrobial resistance (AMR). A common feature of human pathogens is the ability to form biofilm, which poses a serious medical issue due to their high susceptibility to traditional antibiotics. Because QS is associated with virulence and biofilm formation, there is a belief that inhibition of QS activity called quorum quenching (QQ) may provide alternative therapeutic methods for treating microbial infections. This review summarises recent progress in biofilm research, focusing on the mechanisms by which biofilms, especially those formed by pathogenic bacteria, become resistant to antibiotic treatment. Subsequently, a potential alternative approach to QS inhibition highlighting innovative non-antibiotic strategies to control AMR and biofilm formation of pathogenic bacteria has been discussed.

The normality assumption on between-study random effects was questionable in a considerable number of Cochrane meta-analyses.

BACKGROUND: Studies included in a meta-analysis are often heterogeneous. The traditional random-effects models assume their true effects to follow a normal distribution, while it is unclear if this critical assumption is practical. Violations of this between-study normality assumption could lead to problematic meta-analytical conclusions. We aimed to empirically examine if this assumption is valid in published meta-analyses. METHODS: In this cross-sectional study, we collected meta-analyses available in the Cochrane Library with at least 10 studies and with between-study variance estimates > 0. For each extracted meta-analysis, we performed the Shapiro-Wilk (SW) test to quantitatively assess the between-study normality assumption. For binary outcomes, we assessed between-study normality for odds ratios (ORs), relative risks (RRs), and risk differences (RDs). Subgroup analyses based on sample sizes and event rates were used to rule out the potential confounders. In addition, we obtained the quantile-quantile (Q-Q) plot of study-specific standardized residuals for visually assessing between-study normality. RESULTS: Based on 4234 eligible meta-analyses with binary outcomes and 3433 with non-binary outcomes, the proportion of meta-analyses that had statistically significant non-normality varied from 15.1 to 26.2%. RDs and non-binary outcomes led to more frequent non-normality issues than ORs and RRs. For binary outcomes, the between-study non-normality was more frequently found in meta-analyses with larger sample sizes and event rates away from 0 and 100%. The agreements of assessing the normality between two independent researchers based on Q-Q plots were fair or moderate. CONCLUSIONS: The between-study normality assumption is commonly violated in Cochrane meta-analyses. This assumption should be routinely assessed when performing a meta-analysis. When it may not hold, alternative meta-analysis methods that do not make this assumption should be considered.

Biofilm formation in xenobiotic-degrading microorganisms.

The increased presence of xenobiotics affects living organisms and the environment at large on a global scale. Microbial degradation is effective for the removal of xenobiotics from the ecosystem. In natural habitats, biofilms are formed by single or multiple populations attached to biotic/abiotic surfaces and interfaces. The attachment of microbial cells to these surfaces is possible via the matrix of extracellular polymeric substances (EPSs). However, the molecular machinery underlying the development of biofilms differs depending on the microbial species. Biofilms act as biocatalysts and degrade xenobiotic compounds, thereby removing them from the environment. Quorum sensing (QS) helps with biofilm formation and is linked to the development of biofilms in natural contaminated sites. To date, scant information is available about the biofilm-mediated degradation of toxic chemicals from the environment. Therefore, we review novel insights into the impact of microbial biofilms in xenobiotic contamination remediation, the regulation of biofilms in contaminated sites, and the implications for large-scale xenobiotic compound treatment.

Quorum sensing unveils the sludge floccule-assisted stabilization of aerobic granules in granule-dominated sequencing batch reactors.

Floccules are another major form of microbial aggregates in aerobic granular sludge systems. Previous studies mainly attributed the persistence of floccules to their relatively faster nutrient uptake and higher growth rate over aerobic granules; however, they failed to unravel the underlying mechanism of the long-term coexistence of these two aggregates. In this work, the existence and function of the floccules in an aerobic granule-dominated sequencing batch reactor were investigated from the view of quorum sensing (QS) and quorum quenching (QQ). The results showed that though the floccules were closely associated with the granules in terms of similar community structures (including the QS- and QQ-related ones), they exhibited a relatively higher QQ-related activity but a lower QS-related activity. A compatible proportion of floccules might be helpful to maintain the QS-related activity and keep the granules stable. In addition, the structure difference was demonstrated to diversify the QS- and QQ-related activities of the floccules and the aerobic granules. These findings could broaden our understanding of the interactions between the coexistent floccules and granules in aerobic granule-dominated systems and would be instructive for the development of the aerobic granular sludge process.

Patient experience of virtual urogynaecology services during Covid-19 pandemic.

INTRODUCTION AND HYPOTHESIS: Due to increasing burden on outpatient services, there is a drive from NHS policy makers to utilise virtual clinics to help curb unsustainable demand. During the COVID-19 pandemic, urogynaecology clinics were converted to telephone consultation (TC). We used this opportunity to evaluate patient perspective and identify which patients may be best suited to TC. METHODS: Postal questionnaires were sent to patients following urogynaecology TCs in May to June 2020. Clinical outcome data were obtained from electronic records. The survey combined three validated tools: QQ-10, Patient Enablement Index (PEI) and NHS Friends and Family Test (NHS-FFT). Qualitative and quantitative data were analysed. RESULTS: Of the 308 patients contacted, 165 responded (54%). Eighty-six percent of patients described their experience of TC as "very good" or "good" (NHS-FFT). Positive themes included convenience, thoroughness and feeling at ease in terms of communicating intimate symptoms. QQ-10 results demonstrated a mean value score of 77 and a mean burden score of 17 (range 0-100); 72% of patients "strongly" or "mostly" agreed to repeat TC. Following TC, 22% of patients were discharged, 72% required follow-up and 37% needed face-to-face (F2F) consultation. Post-operative patients and those with lower urinary tract symptoms benefited most, whereas many prolapse patients required F2F consultation. CONCLUSIONS: We report the largest qualitative and quantitative study of patient experience of TC in urogynaecology. TC is a convenient, acceptable and effective medium for conducting patient care. TC can support patients in communicating intimate symptoms with health professionals.

Reducing the virulence of Pseudomonas aeruginosa by using multiple quorum-quenching enzymes.

The emergence of multidrug-resistant Pseudomonas aeruginosa in healthcare settings poses a tremendous challenge to traditional antibiotic therapy. Pseudomonas aeruginosa utilizes quorum sensing (QS) to coordinate the production of virulence factors and the formation of drug-resistant biofilms. QS is mediated by signal compounds produced by P. aeruginosa as well as signal molecules produced by other non-pseudomonad bacteria. A potential strategy to prevent bacterial pathogenicity is utilizing enzymes to interfere with QS. Here, we used AidC, a quorum-quenching (QQ) enzyme from Chryseobacterium sp. strain StRB126 that can effectively hydrolyze N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL) and N-butanoyl-homoserine lactone (C4-HSL), the major signal molecules synthesized by P. aeruginosa. The exogenous addition of AidC to P. aeruginosa wild-type strain PAO1 cultures significantly reduced the total protease and elastase activities and the production of pyocyanin. In addition, the application of AidC resulted in thin and sparse biofilm formation. Later, we used a metagenomic-derived QQ enzyme, QQ-2, in combination with AidC to attenuate PAO1 virulence when the presence of a non-pseudomonad signal compound, autoinducer-2, aggravated it. These findings suggest that using a combined antimicrobial approach may lead to a more efficacious therapeutic intervention against P. aeruginosa PAO1 infection, as its behavior is modulated in the presence of intraspecies and interspecies signal compounds. ONE-SENTENCE SUMMARY: In this work, the potential of dual enzymes was investigated to interfere with quorum sensing as a novel concept for reducing the virulence of P. aeruginosa, which is influenced by both intra species and interspecies communication.

Application of Equal Local Levels to Improve Q-Q Plot Testing Bands with R Package qqconf.

Quantile-Quantile (Q-Q) plots are often difficult to interpret because it is unclear how large the deviation from the theoretical distribution must be to indicate a lack of fit. Most Q-Q plots could benefit from the addition of meaningful global testing bands, but the use of such bands unfortunately remains rare because of the drawbacks of current approaches and packages. These drawbacks include incorrect global Type I error rate, lack of power to detect deviations in the tails of the distribution, relatively slow computation for large data sets, and limited applicability. To solve these problems, we apply the equal local levels global testing method, which we have implemented in the R Package qqconf, a versatile tool to create Q-Q plots and probability-probability (P-P) plots in a wide variety of settings, with simultaneous testing bands rapidly created using recently-developed algorithms. qqconf can easily be used to add global testing bands to Q-Q plots made by other packages. In addition to being quick to compute, these bands have a variety of desirable properties, including accurate global levels, equal sensitivity to deviations in all parts of the null distribution (including the tails), and applicability to a range of null distributions. We illustrate the use of qqconf in several applications: assessing normality of residuals from regression, assessing accuracy of p values, and use of Q-Q plots in genome-wide association studies.

QQ-NET - using deep learning to solve quantitative susceptibility mapping and quantitative blood oxygen level dependent magnitude (QSM+qBOLD or QQ) based oxygen extraction fraction (OEF) mapping.

PURPOSE: To improve accuracy and speed of quantitative susceptibility mapping plus quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) -based oxygen extraction fraction (OEF) mapping using a deep neural network (QQ-NET). METHODS: The 3D multi-echo gradient echo images were acquired in 34 ischemic stroke patients and 4 healthy subjects. Arterial spin labeling and diffusion weighted imaging (DWI) were also performed in the patients. NET was developed to solve the QQ model inversion problem based on Unet. QQ-based OEF maps were reconstructed with previously introduced temporal clustering, tissue composition, and total variation (CCTV) and NET. The results were compared in simulation, ischemic stroke patients, and healthy subjects using a two-sample Kolmogorov-Smirnov test. RESULTS: In the simulation, QQ-NET provided more accurate and precise OEF maps than QQ-CCTV with 150 times faster reconstruction speed. In the subacute stroke patients, OEF from QQ-NET had greater contrast-to-noise ratio (CNR) between DWI-defined lesions and their unaffected contralateral normal tissue than with QQ-CCTV: 1.9 ± 1.3 vs 6.6 ± 10.7 (p = 0.03). In healthy subjects, both QQ-CCTV and QQ-NET provided uniform OEF maps. CONCLUSION: QQ-NET improves the accuracy of QQ-based OEF with faster reconstruction.

The protective effects of NE 52-QQ57 against interleukin-33-induced inflammatory response in activated synovial mast cells.

Cytokines-mediated immunity is essential for the pathological development of rheumatoid arthritis (RA). Inhibition of signaling has suggested a potential remedial approach to RA. G protein-coupled receptor 4 (GPR4) has been proven to possess a broad range of physiological functions, but its function in synovial mast cells and RA is less reported. In this study, the protective effects of NE 52-QQ57, a GPR4 antagonist, against interleukin (IL)-33-challenged inflammatory response in activated synovial mast cells were investigated. We report that IL-33 amplified GPR4 expression in HMC-1 mast cells. The GPR4 antagonist NE 52-QQ57 alleviated IL-33-caused secretions of IL-17, interferon-γ, and tumor necrosis factor-α in HMC-1 mast cells. Furthermore, we note that NE 52-QQ57 reduced IL-33-induced expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Also, NE 52-QQ57 inhibited cyclooxygenase 2 and prostaglandin E2 expression in IL-33-challenged cells. Also, NE 52-QQ57 ameliorated IL-33-induced oxidative stress by reducing mitochondrial reactive oxygen species and 4-hydroxynonenal. Mechanistically, NE 52-QQ57 mitigated IL-33-induced activation of the p38/nuclear factor-κB signaling pathway. We conclude that targeting GPR4 might be a promising strategy for RA treatment.

Cerebral oxygen extraction fraction: Comparison of dual-gas challenge calibrated BOLD with CBF and challenge-free gradient echo QSM+qBOLD.

PURPOSE: To compare cortical gray matter oxygen extraction fraction (OEF) estimated from 2 MRI methods: (1) the quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level dependent imaging (qBOLD) (QSM+qBOLD or QQ), and (2) the dual-gas calibrated-BOLD (DGCB) in healthy subjects; and to investigate the validity of iso-cerebral metabolic rate of oxygen consumption assumption during hypercapnia using QQ. METHODS: In 10 healthy subjects, 3 tesla MRI including a multi-echo gradient echo sequence at baseline and hypercapnia for QQ, as well as an EPI dual-echo pseudo-continuous arterial spin labeling for DGCB, were performed under a hypercapnic and a hyperoxic condition. OEFs from QQ and DGCB were compared using region of interest analysis and paired t test. For QQ, cerebral metabolic rate of oxygen consumption = cerebral blood flow*OEF*arterial oxygen content was generated for both baseline and hypercapnia, which were compared. RESULTS: Average OEF in cortical gray matter across 10 subjects from QQ versus DGCB was 35.5 ± 6.7% versus 38.0 ± 9.1% (P = .49) at baseline and 20.7 ± 4.4% versus 28.4 ± 7.6% (P = .02) in hypercapnia: OEF in cortical gray matter was significantly reduced as measured in QQ (P < .01) and in DGCB (P < .01). Cerebral metabolic rate of oxygen consumption (in µmol O2 /min/100 g) was 168.2 ± 54.1 at baseline from DGCB and was 153.1 ± 33.8 at baseline and 126.4 ± 34.2 (P < .01) in hypercapnia from QQ. CONCLUSION: The differences in OEF obtained from QQ and DGCB are small and nonsignificant at baseline but are statistically significant during hypercapnia. In addition, QQ shows a cerebral metabolic rate of oxygen consumption decrease (17.4%) during hypercapnia.

Patient experience of telephone consultations in gynaecology: a service evaluation.

OBJECTIVE: To investigate patient perspective of telephone consultations (TCs) in gynaecology and identify which patients benefit most from a telemedicine system. DESIGN: Service evaluation. SETTING: Gynaecology outpatient services at a tertiary referral hospital. POPULATION: Patients who received a TC during May and June 2020. METHODS: Postal questionnaire combining three validated tools: QQ-10, Patient Enablement Index (PEI) and National Health Service Friends and Family Test (NHS-FFT). Quantitative data and free text responses were analysed. MAIN OUTCOME MEASURES: Responses to QQ-10, PEI and NHS-FFT. RESULTS: In total, 1307 patients were contacted and 504 patients responded (39%). Most (89%) described their experience as 'Very good' or 'Good' (NHS-FFT). Positive themes from responses included 'convenience', 'effectiveness' and 'equivalent care'. QQ-10 responses demonstrated a high Value score of 79 (0-100) and a low Burden score of 15. PEI scores suggested that most patients felt better or much better able to understand and cope with their condition following TC. The majority of patients (77%) would 'Strongly agree' or 'Mostly agree' to a repeat TC. Regarding patient outcomes, 21% were discharged and 71% required follow up. Menopause, fertility and endometriosis follow-up clinic patients benefited most from TC. Gynaecology-oncology patients found TC least acceptable. CONCLUSION: We report a large questionnaire survey of patient experience of TC in gynaecology. Telemedicine is convenient, acceptable and effective for conducting care in selected groups. TC can support patients in communicating intimate symptoms. TWEETABLE ABSTRACT: Telephone consultations are a convenient, acceptable and effective medium for conducting patient care in gynaecology.

Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24-hour Holter monitoring: A multicenter cross-sectional study.

BACKGROUND: The clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype-specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12-lead ECG. OBJECTIVES: This study aims to evaluate the utility of QT/RR slope analysis by the 24-hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2. METHODS: This cross-sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT-apex (QTa) interval and the QT-end (QTe) interval at each 15-second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24-hour and separately during the day or night-time periods of the Holter recordings. RESULTS: The QTe/RR and QTa/RR slopes at the entire 24-hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24-hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68-0.93]). CONCLUSION: The continuous 24-hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.

Preparation of a mesoporous silica quorum quenching medium for wastewater treatment using a membrane bioreactor.

Various quorum quenching (QQ) media have been developed to mitigate membrane biofouling in a membrane bioreactor (MBR). However, most are expensive, unstable and easily trapped in hollow fibre membranes. Here, a sol-gel method was used to develop a mesoporous silica medium entrapping a QQ bacterial strain (Rhodococcus sp. BH4). The new silica QQ medium was able to remove quorum sensing signalling molecules via both adsorption (owing to their mesoporous hydrophobic structure) and decomposition with an enzyme (lactonase), preventing MBR biofouling without affecting the water quality. It also demonstrated a relatively long life span due to its non-biodegradability and its relatively small particle size (<1.0 mm), which makes it less likely to clog in a hollow fibre membrane module.

Saline Environments as a Source of Potential Quorum Sensing Disruptors to Control Bacterial Infections: A Review.

Saline environments, such as marine and hypersaline habitats, are widely distributed around the world. They include sea waters, saline lakes, solar salterns, or hypersaline soils. The bacteria that live in these habitats produce and develop unique bioactive molecules and physiological pathways to cope with the stress conditions generated by these environments. They have been described to produce compounds with properties that differ from those found in non-saline habitats. In the last decades, the ability to disrupt quorum-sensing (QS) intercellular communication systems has been identified in many marine organisms, including bacteria. The two main mechanisms of QS interference, i.e., quorum sensing inhibition (QSI) and quorum quenching (QQ), appear to be a more frequent phenomenon in marine aquatic environments than in soils. However, data concerning bacteria from hypersaline habitats is scarce. Salt-tolerant QSI compounds and QQ enzymes may be of interest to interfere with QS-regulated bacterial functions, including virulence, in sectors such as aquaculture or agriculture where salinity is a serious environmental issue. This review provides a global overview of the main works related to QS interruption in saline environments as well as the derived biotechnological applications.

Combination of HPLC with organic and inorganic mass spectrometry to study the metabolic response of the clam Scrobicularia plana to arsenic exposure.

Arsenic is a toxic element extensively studied in the marine environment due to differential toxicological effects of inorganic and organic species. In the present work, the bivalve Scrobicularia plana was exposed to AsV (10 and 100 µg/L) for 14 days to evaluate the metabolic perturbations caused by this element. Arsenic speciation and metabolomic analysis were performed in the digestive gland of the bivalve using two complementary analytical platforms based on inorganic and organic mass spectrometry. It has been observed the greater presence of the innocuous specie arsenobetaine produced in this organism as defense mechanism against arsenic toxicity, although significant concentrations of methylated and inorganic arsenic were also present, depending on the level of arsenic in aqueous media. Complementarily, a metabolomic study based on mass spectrometry and statistical discriminant analysis allows a good classification of samples associated to low and high As(V) exposure in relation to controls. About 15 metabolites suffer significant changes of expression by the presence of As(V): amino acids, nucleotides, energy-related metabolites, free fatty acids, phospholipids and triacylglycerides, which can be related to membrane structural and functional damage. In addition, perturbation of the methylation cycle, associated with the increase of homocysteine and methionine was observed, which enhance the methylation of toxic inorganic arsenic to less toxic dimethylarsenic.

Revealing strategies of quorum sensing in Azospirillum brasilense strains Ab-V5 and Ab-V6.

Azospirillum brasilense is an important plant-growth promoting bacterium (PGPB) that requires several critical steps for root colonization, including biofilm and exopolysaccharide (EPS) synthesis and cell motility. In several bacteria these mechanisms are mediated by quorum sensing (QS) systems that regulate the expression of specific genes mediated by the autoinducers N-acyl-homoserine lactones (AHLs). We investigated QS mechanisms in strains Ab-V5 and Ab-V6 of A. brasilense, which are broadly used in commercial inoculants in Brazil. Neither of these strains carries a luxI gene, but there are several luxR solos that might perceive AHL molecules. By adding external AHLs we verified that biofilm and EPS production and cell motility (swimming and swarming) were regulated via QS in Ab-V5, but not in Ab-V6. Differences were observed not only between strains, but also in the specificity of LuxR-type receptors to AHL molecules. However, Ab-V6 was outstanding in indole acetic acid (IAA) synthesis and this molecule might mimic AHL signals. We also applied the quorum quenching (QQ) strategy, obtaining transconjugants of Ab-V5 and Ab-V6 carrying a plasmid with acyl-homoserine lactonase. When maize (Zea mays L.) was inoculated with the wild-type and transconjugant strains, plant growth was decreased with the transconjugant of Ab-V5-confirming the importance of an AHL-mediated QS system-but did not affect plant growth promotion by Ab-V6.

The Doctor Is In! Diagnostic Analysis.

To make meaningful inferences based on our regression models, we must ensure that we have met the necessary assumptions of these tests. In this commentary, we review these assumptions and those for the t-test and analysis of variance, and introduce a variety of methods, formal and informal, numeric and visual, for assessing conformity with the assumptions.

A Framework for Interpreting Type I Error Rates from a Product-Term Model of Interaction Applied to Quantitative Traits.

Adequate control of type I error rates will be necessary in the increasing genome-wide search for interactive effects on complex traits. After observing unexpected variability in type I error rates from SNP-by-genome interaction scans, we sought to characterize this variability and test the ability of heteroskedasticity-consistent standard errors to correct it. We performed 81 SNP-by-genome interaction scans using a product-term model on quantitative traits in a sample of 1,053 unrelated European Americans from the NHLBI Family Heart Study, and additional scans on five simulated datasets. We found that the interaction-term genomic inflation factor (lambda) showed inflation and deflation that varied with sample size and allele frequency; that similar lambda variation occurred in the absence of population substructure; and that lambda was strongly related to heteroskedasticity but not to minor non-normality of phenotypes. Heteroskedasticity-consistent standard errors narrowed the range of lambda, with HC3 outperforming HC0, but in individual scans tended to create new P-value outliers related to sparse two-locus genotype classes. We explain the lambda variation as a result of non-independence of test statistics coupled with stochastic biases in test statistics due to a failure of the test to reach asymptotic properties. We propose that one way to interpret lambda is by comparison to an empirical distribution generated from data simulated under the null hypothesis and without population substructure. We further conclude that the interaction-term lambda should not be used to adjust test statistics and that heteroskedasticity-consistent standard errors come with limitations that may outweigh their benefits in this setting.