Experimental Designs to Study the Aggregation and Colonization of Biofilms by Video Microscopy With Statistical Confidence

The goal of this study was to quantify the variability of confocal laser scanning microscopy (CLSM) time-lapse images of early colonizing biofilms to aid in the design of future imaging experiments. To accomplish this a large imaging dataset consisting of 16 independent CLSM microscopy experiments was leveraged. These experiments were designed to study interactions between human neutrophils and single cells or aggregates of Staphylococcus aureus (S. aureus) during the initial stages of biofilm formation. Results suggest that in untreated control experiments, variability differed substantially between growth phases (i.e., lag or exponential). When studying the effect of an antimicrobial treatment (in this case, neutrophil challenge), regardless of the inoculation level or of growth phase, variability changed as a frown-shaped function of treatment efficacy (i.e., the reduction in biofilm surface coverage). These findings were used to predict the best experimental designs for future imaging studies of early biofilms by considering differing (i) numbers of independent experiments; (ii) numbers of fields of view (FOV) per experiment; and (iii) frame capture rates per hour. A spreadsheet capable of assessing any user-specified design is included that requires the expected mean log reduction and variance components from user-generated experimental results. The methodology outlined in this study can assist researchers in designing their CLSM studies of antimicrobial treatments with a high level of statistical confidence.

Human-caused long-term changes in global aridity

Widespread aridification of the land surface causes substantial environmental challenges and is generally well documented. However, the mechanisms underlying increased aridity remain relatively underexplored. Here, we investigated the anthropogenic and natural factors affecting long-term global aridity changes using multisource observation-based aridity index, factorial simulations from the Coupled Model Intercomparison Project phase 6 (CMIP6), and rigorous detection and attribution (D&A) methods. Our study found that anthropogenic forcings, mainly rising greenhouse gas emissions (GHGE) and aerosols, caused the increased aridification of the globe and each hemisphere with high statistical confidence for 1965–2014; the GHGE contributed to drying trends, whereas the aerosol emissions led to wetting tendencies; moreover, the bias-corrected CMIP6 future aridity index based on the scaling factors from optimal D&A demonstrated greater aridification than the original simulations. These findings highlight the dominant role of human effects on increasing aridification at broad spatial scales, implying future reductions in aridity will rely primarily on the GHGE mitigation.

Extending the Scope of Robust Quadratic Optimization

We derive computationally tractable formulations of the robust counterparts of convex quadratic and conic quadratic constraints that are concave in matrix-valued uncertain parameters. We do this for a broad range of uncertainty sets. Our results provide extensions to known results from the literature. We also consider hard quadratic constraints: those that are convex in uncertain matrix-valued parameters. For the robust counterpart of such constraints, we derive inner and outer tractable approximations. As an application, we show how to construct a natural uncertainty set based on a statistical confidence set around a sample mean vector and covariance matrix and use this to provide a tractable reformulation of the robust counterpart of an uncertain portfolio optimization problem. We also apply the results of this paper to norm approximation problems. Summary of Contribution: This paper develops new theoretical results and algorithms that extend the scope of a robust quadratic optimization problem. More specifically, we derive computationally tractable formulations of the robust counterparts of convex quadratic and conic quadratic constraints that are concave in matrix-valued uncertain parameters. We also consider hard quadratic constraints: those that are convex in uncertain matrix-valued parameters. For the robust counterpart of such constraints, we derive inner and outer tractable approximations.

Specific splice junction detection in single cells with SICILIAN

Precise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but are critical for understanding single-cell biology. Here, we introduce SICILIAN, a new method that assigns statistical confidence to splice junctions from a spliced aligner to improve precision. SICILIAN is a general method that can be applied to bulk or single-cell data, but has particular utility for single-cell analysis due to that data’s unique challenges and opportunities for discovery. SICILIAN’s precise splice detection achieves high accuracy on simulated data, improves concordance between matched single-cell and bulk datasets, and increases agreement between biological replicates. SICILIAN detects unannotated splicing in single cells, enabling the discovery of novel splicing regulation through single-cell analysis workflows.

Comparative Effectiveness of Initial Treatment for Infantile Spasms in a Contemporary US Cohort

Objective.Compare the effectiveness of initial treatment for infantile spasms.Methods.The National Infantile Spasms Consortium prospectively followed children with new onset infantile spasms that began at age 2-24 months at 23 US centers (2012-2018). Freedom from treatment failure at 60 days required no second treatment for infantile spasms and no clinical spasms after 30 days of treatment initiation. We managed treatment selection bias with propensity score weighting and within-center correlation with generalized estimating equations.Results.Freedom from treatment failure rates were: ACTH 88/190 (46%), oral steroids 42/95 (44%), vigabatrin 32/87 (37%), and non-standard therapy 4/51 (8%). Changing from oral steroids to ACTH was not estimated to affect response (observed 44% estimated to change to 44% [95% CI 34–54]). Changing from non-standard therapy to ACTH would improve response from 8% to 39 [17–67]%, and to oral steroids from 8% to 38 [15–68]%. There were large but not statistically significant estimated effects of changing from vigabatrin to ACTH (29% to 42 [15–75]%), vigabatrin to oral steroids (29% to 42 [28–57]%), and non-standard therapy to vigabatrin (8% to 20 [6-50]%). Among children treated with vigabatrin, those with tuberous sclerosis complex (TSC) responded more often than others (62% vs 29%; p<0.05)Conclusion.Compared to non-standard therapy, ACTH and oral steroids are superior for initial treatment of infantile spasms. The estimated effectiveness of vigabatrin is between ACTH / oral steroids and non-standard therapy, though the sample was underpowered for statistical confidence. When used, vigabatrin worked best for TSC.Classification of Evidence:This study provides Class III evidence that for children with new onset infantile spasms, ACTH or oral steroids were superior to non-standard therapies.

Prevalence and Impact of Biofilms on Bloodstream and Urinary Tract Infections: A Systematic Review and Meta-Analysis

This study sought to assess the prevalence and impact of biofilms on two commonly biofilm-related infections, bloodstream and urinary tract infections (BSI and UTI). Separated systematic reviews and meta-analyses of observational studies were carried out in PubMed and Web of Sciences databases from January 2005 to May 2020, following PRISMA protocols. Studies were selected according to specific and defined inclusion/exclusion criteria. The obtained outcomes were grouped into biofilm production (BFP) prevalence, BFP in resistant vs. susceptible strains, persistent vs. non-persistent BSI, survivor vs. non-survivor patients with BSI, and catheter-associated UTI (CAUTI) vs. non-CAUTI. Single-arm and two-arm analyses were conducted for data analysis. In vitro BFP in BSI was highly related to resistant strains (odds ratio-OR: 2.68; 95% confidence intervals-CI: 1.60–4.47; p < 0.01), especially for methicillin-resistant Staphylococci. BFP was also highly linked to BSI persistence (OR: 2.65; 95% CI: 1.28–5.48; p < 0.01) and even to mortality (OR: 2.05; 95% CI: 1.53–2.74; p < 0.01). Candida spp. was the microorganism group where the highest associations were observed. Biofilms seem to impact Candida BSI independently from clinical differences, including treatment interventions. Regarding UTI, multi-drug resistant and extended-spectrum β-lactamase-producing strains of Escherichia coli, were linked to a great BFP prevalence (OR: 2.92; 95% CI: 1.30–6.54; p < 0.01 and OR: 2.80; 95% CI: 1.33–5.86; p < 0.01). More in vitro BFP was shown in CAUTI compared to non-CAUTI, but with less statistical confidence (OR: 2.61; 95% CI: 0.67–10.17; p < 0.17). This study highlights that biofilms must be recognized as a BSI and UTI resistance factor as well as a BSI virulence factor.

An Examination of Asymmetry in Adult Tympanometric Measures

Background During audiologic evaluations, an examination of interaural asymmetry is commonly evaluated. To date, however, interaural differences for tympanometric indices have not been reported for adults. Without documented tympanometric right-left differences, one cannot determine if asymmetries are normal or are indicative of significant clinical asymmetries. Purpose The purpose of this study was to investigate interaural asymmetries in peak compensated static acoustic admittance (Ytm), equivalent ear canal volume (Vea), tympanometric peak pressure (TPP), and tympanometric width (TW) in normal adults. Research Design Descriptive, correlational, and inferential measures designs were employed. Study Sample Participants were 188 otologically normal Caucasian young adults (i.e., 77 females and 111 males; M = 23.0 years, standard deviation [SD] = 2.7, range = 18–30 years). Data Collection and Analyses Ytm, Vea, TPP, and TW measures were obtained bilaterally from an admittance tympanogram using a 226 Hz probe tone. Separate two-factor mixed measures analysis of variance examined the effect of ear and sex for each tympanometric index. Correlation analyses examined the association between right and left ear indices. Interaural differences in tympanometric indices were examined with independent t-tests. Critical differences, for deciding if two tympanometric indices are different between ears, were computed from the standard deviations of the right–left ear difference for statistical confidence levels of 85, 90, 95, and 99%. Results The effect of ear was not statistically significant (p > 0.05) on any tympanometric index. Females had significantly lower Ytm and smaller Vea measures than males (p < 0.05). Correlations between all right and left tympanometric indices were positive and statistically significant (p < 0.05). There were no statistically significant differences in interaural differences for any of the tympanometric indices as a function of sex (p > 0.05). Critical differences, for confidence levels for 85% to 99% confidence ranged from ± 0.20–0.36 mmhos for Ytm, ± 0.23–0.41 cm3 for Vea, ± 11.1–19.8 daPa for TPP, and ± 27.2–48.7 daPa for TW. Conclusion A clinician can use these critical differences to determine if tympanometric index interaural differences in ears of young normal Caucasian adults are statistically significant.

Analysis of machining-induced residual stresses of milled aluminum workpieces, their repeatability, and their resulting distortion

Machining-induced residual stresses (MIRS) are a main driver for distortion of thin-walled monolithic aluminum workpieces. Before one can develop compensation techniques to minimize distortion, the effect of machining on the MIRS has to be fully understood. This means that not only an investigation of the effect of different process parameters on the MIRS is important. In addition, the repeatability of the MIRS resulting from the same machining condition has to be considered. In past research, statistical confidence of MIRS of machined samples was not focused on. In this paper, the repeatability of the MIRS for different machining modes, consisting of a variation in feed per tooth and cutting speed, is investigated. Multiple hole-drilling measurements within one sample and on different samples, machined with the same parameter set, were part of the investigations. Besides, the effect of two different clamping strategies on the MIRS was investigated. The results show that an overall repeatability for MIRS is given for stable machining (between 16 and 34% repeatability standard deviation of maximum normal MIRS), whereas instable machining, detected by vibrations in the force signal, has worse repeatability (54%) independent of the used clamping strategy. Further experiments, where a 1-mm-thick wafer was removed at the milled surface, show the connection between MIRS and their distortion. A numerical stress analysis reveals that the measured stress data is consistent with machining-induced distortion across and within different machining modes. It was found that more and/or deeper MIRS cause more distortion.

Impact of COVID-19 lockdown on body mass index in young adults

Background and Study Aim. We conducted our research on the supposition that in pandemic context the student’s weight might increase, influencing consequently BMI values. For the present moment humankind must cope with important changes and regulation which have massively impacted our daily lives. Social distancing measures taken in many schools and universities for limiting exposure and transmission coronavirus run counter how the education process is operating usually. The question that this context rises is: how people in general and especially young people are coping with this lack of physical activity and physical education changes? Material and Methods. In this study were involved 176 male university students, 19.3±0.67 years of age, divided in two equal groups: the first one measured in 2018, with regular physical activity in face-to-face mode and the second one measured in the end of 2020, after almost one year of remote learning. Results. In between the two measurements the BMI increased with 1.8 kg/m2, primarily because weight gain. It results that in just two years the percentage of young men with weight issues had a significant increase from 19.3% to 33%. Applying Bonferroni correction for two tests and p < 0.05 it turns out that the two data samples are different with a statistical confidence >95%. Conclusions. Under the pandemic circumstances the energy balance between food consumption and physical activity was seriously disturbed, resulting in an increased BMI. Our results confirm this tendency presented in other studies on samples of adolescents and young adults, from different countries and regions.