Improving the Accuracy of Bulk Fitness Assays by Correcting Barcode Processing Biases.

Measuring the fitnesses of genetic variants is a fundamental objective in evolutionary biology. A standard approach for measuring microbial fitnesses in bulk involves labeling a library of genetic variants with unique sequence barcodes, competing the labeled strains in batch culture, and using deep sequencing to track changes in the barcode abundances over time. However, idiosyncratic properties of barcodes can induce nonuniform amplification or uneven sequencing coverage that causes some barcodes to be over- or under-represented in samples. This systematic bias can result in erroneous read count trajectories and misestimates of fitness. Here, we develop a computational method, named REBAR (Removing the Effects of Bias through Analysis of Residuals), for inferring the effects of barcode processing bias by leveraging the structure of systematic deviations in the data. We illustrate this approach by applying it to two independent data sets, and demonstrate that this method estimates and corrects for bias more accurately than standard proxies, such as GC-based corrections. REBAR mitigates bias and improves fitness estimates in high-throughput assays without introducing additional complexity to the experimental protocols, with potential applications in a range of experimental evolution and mutation screening contexts.

Evolutionary "Crowdsourcing": Alignment of Fitness Landscapes Allows for Cross-species Adaptation of a Horizontally Transferred Gene.

Genes that undergo horizontal gene transfer (HGT) evolve in different genomic backgrounds. Despite the ubiquity of cross-species HGT, the effects of switching hosts on gene evolution remains understudied. Here, we present a framework to examine the evolutionary consequences of host-switching and apply this framework to an antibiotic resistance gene commonly found on conjugative plasmids. Specifically, we determined the adaptive landscape of this gene for a small set of mutationally connected genotypes in 3 enteric species. We uncovered that the landscape topographies were largely aligned with minimal host-dependent mutational effects. By simulating gene evolution over the experimentally gauged landscapes, we found that the adaptive evolution of the mobile gene in one species translated to adaptation in another. By simulating gene evolution over artificial landscapes, we found that sufficient alignment between landscapes ensures such "adaptive equivalency" across species. Thus, given adequate landscape alignment within a bacterial community, vehicles of HGT such as plasmids may enable a distributed form of genetic evolution across community members, where species can "crowdsource" adaptation.

Model-driven mitigation measures for reopening schools during the COVID-19 pandemic.

Reopening schools is an urgent priority as the COVID-19 pandemic drags on. To explore the risks associated with returning to in-person learning and the value of mitigation measures, we developed stochastic, network-based models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in primary and secondary schools. We find that a number of mitigation measures, alone or in concert, may reduce risk to acceptable levels. Student cohorting, in which students are divided into two separate populations that attend in-person classes on alternating schedules, can reduce both the likelihood and the size of outbreaks. Proactive testing of teachers and staff can help catch introductions early, before they spread widely through the school. In secondary schools, where the students are more susceptible to infection and have different patterns of social interaction, control is more difficult. Especially in these settings, planners should also consider testing students once or twice weekly. Vaccinating teachers and staff protects these individuals and may have a protective effect on students as well. Other mitigations, including mask wearing, social distancing, and increased ventilation, remain a crucial component of any reopening plan.

Proactive COVID-19 testing in a partially vaccinated population

During the initial stages of the COVID-19 pandemic, many workplaces and universities implemented institution-wide proactive testing programs of all individuals, ir-respective of symptoms. These measures have proven effective in mitigating outbreaks. As a greater fraction of the population becomes vaccinated, we need to understand what continued benefit, if any, proactive testing can contribute. Here, we address this problem with two distinct modeling approaches: a simple analytical model and a more simulation using the SEIRS+ platform. Both models indicate that proactive testing remains useful until a threshold level of vaccination is reached. This threshold depends on the transmissibility of the virus and the scope of other control measures in place. If a community is able to reach the threshold level of vaccination, testing can cease. Otherwise, continued testing will be an important component of disease control. Because it is usually difficult or impossible to precisely estimate key parameters such as the basic reproduction number for a specific workplace or other setting, our results are more useful for understanding general trends than for making precise quantitative predictions.

Model-driven mitigation measures for reopening schools during the COVID-19 pandemic

Reopening schools is an urgent priority as the COVID-19 pandemic drags on. To explore the risks associated with returning to in-person learning and the value of mitigation measures, we developed stochastic, network-based models of SARS-CoV-2 transmission in primary and secondary schools. We find that a number of mitigation measures, alone or in concert, may reduce risk to acceptable levels. Student cohorting, in which students are divided into two separate populations that attend in-person classes on alternating schedules, can reduce both the likelihood and the size of outbreaks. Proactive testing of teachers and staff can help catch introductions early, before they spread widely through the school. In secondary schools, where the students are more susceptible to infection and have different patterns of social interaction, control is more difficult. Especially in these settings, planners should also consider testing students once or twice weekly. Vaccinating teachers and staff protects these individuals and may have a protective effect on students as well. Other mitigations, including mask-wearing, social distancing, and increased ventilation, remain a crucial component of any reopening plan.

Psychological predictors of pain severity, pain interference, depression, and anxiety in rheumatoid arthritis patients with chronic pain.

OBJECTIVES: Rheumatoid arthritis is a chronic and progressive autoimmune disorder with symptoms sometimes including chronic pain and depression. The current study aimed to explore some of the psychological variables which predict both pain-related outcomes (pain severity and pain interference) and psychological outcomes (depression and anxiety) amongst patients with rheumatoid arthritis experiencing chronic pain. In particular, this study aimed to establish whether either self-concealment, or the satisfaction of basic psychological needs (autonomy, relatedness, and competence), could explain a significant portion of the variance in pain outcomes and psychological outcomes amongst this patient group. DESIGN/METHODS: Online questionnaires were completed by 317 rheumatoid arthritis patients with chronic pain, providing data across a number of predictor and outcome variables. RESULTS: Hierarchical multiple linear regressions indicated that the predictive models for each of the four outcome variables were significant, and had good levels of fit with the data. In terms of individual predictor variables, higher relatedness significantly predicted lower depression, and higher autonomy significantly predicted lower anxiety. CONCLUSIONS: The model generated by this study may identify factors to be targeted by future interventions with the goal of reducing depression and anxiety amongst patients with rheumatoid arthritis experiencing chronic pain. The findings of this study have shown that the autonomy and the relatedness of patients with rheumatoid arthritis play important roles in promoting psychological well-being. Targeted interventions could help to enhance the lives of patients despite the presence of chronic pain. STATEMENT OF CONTRIBUTION: What is already known about the subject? Amongst a sample of chronic pain patients who primarily had a diagnosis of fibromyalgia, it was found that higher levels of self-concealment were associated with higher self-reported pain levels and reduced well-being (as measured by anxiety/depression), and these associations were mediated by patients' needs for autonomy not being met (Uysal & Lu, Health Psychology, 2011, 30, 606). What does this study add? For the first time amongst a rheumatoid arthritis population experiencing chronic pain, we found that higher levels of relatedness significantly predicted lower depression. For the first time amongst the same population, we found that higher levels of autonomy significantly predicted lower anxiety.

Wound care costs in general practice - a cross-sectional study.

BACKGROUND: The management of wounds presents a significant burden to healthcare services, consuming a large amount of resources. This study aimed to determine the cost of wound care in general practice by conducting an audit of current wound management practices. METHODS: Eighteen general practices collected data on wound care episodes over a period of 14 days during December 2011. RESULTS: For most of the 332 wound care episodes, the total cost was greater than the total income, resulting in a net loss to the practice. General practitioner care was the greatest contributor to the total cost and the overwhelming majority of income was from Medicare Benefits Schedule billing items. DISCUSSION: In most cases, general practices are not recouping the costs of wound care. There is a need for policy makers and general practices to review wound care funding and practices to ensure equitable best practice care is being provided.