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Responsive survey design is a technique aimed at improving the efficiency or quality of surveys by using incoming data from the field to make design changes. The technique was pioneered on large national surveys, but the tools can also be applied on the smaller-scale surveys most commonly used by sociologists. We demonstrate responsive survey design in a small-scale, list-based sample survey of students on the topic of sexual misconduct. We investigate the impact of individual incentive levels and a two-phase responsive design with changes to mode of contact as approaches for limiting the potential of nonresponse bias in data from such surveys. Our analyses demonstrate that a two-phase design introducing telephone and face-to-face reminders to complete the survey can produce stronger change in response rates and characteristics of those who respond than higher incentive levels. These findings offer tools for sociologists designing smaller-scale surveys of special populations or sensitive topics.

Genome-wide mutational screens are central to understanding the genetic underpinnings of evolved and engineered phenotypes. The widespread adoption of CRISPR-Cas9 genome editing has enabled such screens in many organisms, but identifying functional sgRNAs still remains a challenge. Here, we developed a methodology to quantify the cutting efficiency of each sgRNA in a genome-scale library, and in doing so improve screens in the biotechnologically important yeast Yarrowia lipolytica. Screening in the presence and absence of native DNA repair enabled high-throughput quantification of sgRNA function leading to the identification of high efficiency sgRNAs that cover 94% of genes. Library validation enhanced the classification of essential genes by identifying inactive guides that create false negatives and mask the effects of successful disruptions. Quantification of guide effectiveness also creates a dataset from which determinants of CRISPR-Cas9 can be identified. Finally, application of the library identified novel mutations for metabolic engineering of high lipid accumulation.

Adaptive survey design refers to using targeted procedures to recruit different sampled cases. This technique strives to reduce bias and variance of survey estimates by trying to recruit a larger and more balanced set of respondents. However, it is not well understood how adaptive design can improve data and survey estimates beyond the well-established post-survey adjustment. This paper reports the results of an experiment that evaluated the additional effect of adaptive design to post-survey adjustments. The experiment was conducted in the Detroit Metro Area Communities Study in 2021. We evaluated the adaptive design in five outcomes: 1) response rates, 2) demographic composition of respondents, 3) bias and variance of key survey estimates, 4) changes in significant results of regression models, and 5) costs. The most significant benefit of the adaptive design was its ability to generate more efficient survey estimates with smaller variances and smaller design effects. [ABSTRACT FROM AUTHOR]

This article presents the results of an adaptive design experiment in the recruitment of households and individuals for a two-stage national probability web or mail mixed-mode survey, the American Family Health Study (AFHS). In the screening stage, we based the adaptive design's subgroup differentiation on Esri Tapestry segmentation. We used tailored invitation materials for a subsample where a high proportion of the population was Hispanic and added a paper questionnaire to the initial mailing for a subsample with rural and older families. In the main-survey stage, the adaptive design targeted the households where a member other than the screening respondent was selected for the survey. The adaptations included emailing and/or texting, an additional prepaid incentive, and seeking screening respondents' help to remind the selected individuals. The main research questions are (i) whether the adaptive design improved survey production outcomes and (ii) whether combining adaptive design and postsurvey weighting adjustments improved survey estimates compared to performing postsurvey adjustments alone. Unfortunately, the adaptive designs did not improve the survey production outcomes. We found that the weighted AFHS estimates closely resemble those of a benchmark national face-to-face survey, the National Survey of Family Growth, although the adaptive design did not additionally change survey estimates beyond the weighting adjustments. Nonetheless, our experiment yields useful insights about the implementation of adaptive design in a self-administered mail-recruit web or mail survey. We were able to identify subgroups with potentially lower response rates and distinctive characteristics, but it was challenging to develop effective protocol adaptations for these subgroups under the constraints of the two primary survey modes and the operational budget of the AFHS. In addition, for self-administered within-household selection, it was difficult to obtain contact information from, reach, and recruit selected household members that did not respond to the screening interview. [ABSTRACT FROM AUTHOR]

Synthetic biology and metabolic engineering seek to re-engineer microbes into living foundries for the production of high value chemicals. Through a design-build-test cycle paradigm, massive libraries of genetically engineered microbes can be constructed and tested for metabolite overproduction and secretion. However, library generation capacity outpaces the rate of high-throughput testing and screening. Well plate assays are flexible but with limited throughput, whereas droplet microfluidic techniques are ultrahigh-throughput but require a custom assay for each target. Here we present RNA-aptamers-in-droplets (RAPID), a method that greatly expands the generality of ultrahigh-throughput microfluidic screening. Using aptamers, we transduce extracellular product titer into fluorescence, allowing ultrahigh-throughput screening of millions of variants. We demonstrate the RAPID approach by enhancing production of tyrosine and secretion of a recombinant protein in Saccharomyces cerevisiae by up to 28- and 3-fold, respectively. Aptamers-in-droplets affords a general approach for evolving microbes to synthesize and secrete value-added chemicals.Screening libraries of genetically engineered microbes for secreted products is limited by the available assay throughput. Here the authors combine aptamer-based fluorescent detection with droplet microfluidics to achieve high throughput screening of yeast strains engineered for enhanced tyrosine or streptavidin production.

Introduction: Workplace exposure to respirable crystalline silica (cSiO2) has been epidemiologically linked to lupus. Consistent with this, repeated subchronic intranasal cSiO2 instillation in lupus-prone NZBWF1 mice induces inflammation-/autoimmune-related gene expression, ectopic lymphoid tissue (ELT), autoantibody (AAb) production in the lung within 5 to 13 wk followed systemic AAb increases and accelerated onset and progression of glomerulonephritis within 13 to 17 wk. Interestingly, dietary docosahexaenoic acid (DHA) supplementation suppresses these pathologic effects, but the underlying molecular mechanisms remain unclear. Methods: This study aimed to test the hypothesis that dietary DHA supplementation impacts acute transcriptional and autoantibody responses in the lungs of female NZBWF1 mice 1 and 4 wk after a single high-dose cSiO2 challenge. Groups of mice were initially fed a control (Con) diet or a DHAcontaining diet (10 g/kg). Cohorts of Con- and DHA-fed were subjected to a single intranasal instillation of 2.5 mg cSiO2 in a saline vehicle (Veh), while a Confed cohort was instilled with Veh only. At 1 and 4 wk post-instillation (PI), we compared cSiO2's effects on innate-/autoimmune-related gene expression and autoantibody (AAb) in lavage fluid/lungs of Con- and DHA-fed mice and related these findings to inflammatory cell profiles, histopathology, cell death, and cytokine/chemokine production. Results: DHA partially alleviated cSiO2-induced alterations in total immune cell and lymphocyte counts in lung lavage fluid. cSiO2-triggered dead cell accumulation and levels of inflammation-associated cytokines and IFN stimulated chemokines were more pronounced in Con-fed mice than DHA-fed mice. Targeted multiplex transcriptome analysis revealed substantial upregulation of genes associated with autoimmune pathways in Con-fed mice in response to cSiO2 that were suppressed in DHA-fed mice. Pathway analysis indicated that DHA inhibited cSiO2 induction of proinflammatory and IFNregulated gene networks, affecting key upstream regulators (e.g., TNFa, IL-1b, IFNAR, and IFNg). Finally, cSiO2-triggered AAb responses were suppressed in DHA-fed mice. Discussion: Taken together, DHA mitigated cSiO2-induced upregulation of pathways associated with proinflammatory and IFN-regulated gene responses within 1 wk and reduced AAb responses by 4 wk. These findings suggest that the acute short-term model employed here holds substantial promise for efficient elucidation of the molecular mechanisms through which omega-3 PUFAs exert protective effects against cSiO2-induced autoimmunity. [ABSTRACT FROM AUTHOR]

Occupational exposure to respirable crystalline silica (cSiO2) has been linked to lupus development. Previous studies in young lupus-prone mice revealed that intranasal cSiO2 exposure triggered autoimmunity, preventable with docosahexaenoic acid (DHA). This study explores cSiO2 and DHA effects in mature lupus-prone adult mice, more representative of cSiO2-exposed worker age. Female NZBWF1 mice (14-week old) were fed control (CON) or DHA-supplemented diets. After two weeks, mice were intranasally instilled saline (VEH) or 1 mg cSiO2 weekly for four weeks. Cohorts were then analyzed 1- and 5-weeks postinstillation for lung inflammation, cell counts, chemokines, histopathology, B- and T-cell infiltration, autoantibodies, and gene signatures, with results correlated to autoimmune glomerulonephritis onset. VEH/CON mice showed no pathology. cSiO2/CON mice displayed significant ectopic lymphoid tissue formation in lungs at 1 week, increasing by 5 weeks. cSiO2/CON lungs exhibited elevated cellularity, chemokines, CD3+ T-cells, CD45R + B-cells, IgG + plasma cells, gene expression, IgG autoantibodies, and glomerular hypertrophy. DHA supplementation mitigated all these effects. The mature adult NZBWF1 mouse used here represents a life-stage coincident with immunological tolerance breach and one that more appropriately represents the age (20–30 yr) of cSiO2-exposed workers. cSiO2-induced robust pulmonary inflammation, autoantibody responses, and glomerulonephritis in mature adult mice, surpassing effects observed previously in young adults. DHA at a human-equivalent dosage effectively countered cSiO2-induced inflammation/autoimmunity in mature mice, mirroring protective effects in young mice. These results highlight life-stage significance in this preclinical lupus model and underscore omega-3 fatty acids' therapeutic potential against toxicant-triggered autoimmune responses. [ABSTRACT FROM AUTHOR]

The control of hydrogen concentration and diffusion in metal alloys is critical for advancing clean energy technologies. A quantitative understanding of the composition–property relationship can accelerate the design of hydrogen storage materials, structural hydrogen-resistant alloys, and materials for energy-efficient nanoelectronics. In this work, we employed Density Functional Theory simulations to investigate the energy landscape of hydrogen absorption and mobility for a wide spectrum of high-entropy alloys and intermetallic compounds. Our study sheds light on the origin of hydrogen stability also providing quantitative guidance for compositional considerations and the design of technologically useful materials. The developed analytical model uses physically intuitive metrics characterizing the local environment, such as electronic structure features, volume of interstitial voids, and lattice vibrational modes, to predict the energy landscape of hydrogen in metal alloys based on simple calculations of bulk properties. The developed model exhibits remarkable accuracy in predicting hydrogen binding energy, achieving a low mean absolute error of less than 0.1 eV. Utilizing this model, we successfully predicted hydrogen absorption energies and migration barriers demonstrating that these quantities are linearly correlated, akin to the Brønsted–Evans–Polanyi principle. In addition, our study revealed that a similar list of material features can be employed to predict zero-point energy contribution associated with hydrogen vibrational motion. [ABSTRACT FROM AUTHOR]

Responsive survey design is a technique aimed at improving the efficiency or quality of surveys by using incoming data from the field to make design changes. The technique was pioneered on large national surveys, but the tools can also be applied on the smaller-scale surveys most commonly used by sociologists. We demonstrate responsive survey design in a small-scale, list-based sample survey of students on the topic of sexual misconduct. We investigate the impact of individual incentive levels and a two-phase responsive design with changes to mode of contact as approaches for limiting the potential of nonresponse bias in data from such surveys. Our analyses demonstrate that a two-phase design introducing telephone and face-to-face reminders to complete the survey can produce stronger change in response rates and characteristics of those who respond than higher incentive levels. These findings offer tools for sociologists designing smaller-scale surveys of special populations or sensitive topics. [ABSTRACT FROM AUTHOR]

In push-to-web surveys that use postal mail to contact sampled cases, participation is contingent on the mail being opened and the survey invitations being delivered. The design of the mailings is crucial to the success of the survey. We address the question of how to design invitation mailings that can grab potential respondents' attention and sway them to be interested in the survey in a short window of time. In the household screening stage of a national survey, the American Family Health Study, we experimentally tested three mailing design techniques for recruiting respondents: (1) a visible cash incentive in the initial mailing, (2) a second incentive for initial nonrespondents, and (3) use of Priority Mail in the nonresponse follow-up mailing. We evaluated the three techniques' overall effects on response rates as well as how they differentially attracted respondents with different characteristics. We found that all three techniques were useful in increasing the screening response rates, but there was little evidence that they had differential effects on sample subgroups that could help to reduce nonresponse biases. [ABSTRACT FROM AUTHOR]

Surveys face difficult choices in managing cost-error trade-offs. Stopping rules for surveys have been proposed as a method for managing these trade-offs. A stopping rule will limit effort on a select subset of cases to reduce costs with minimal harm to quality. Previously proposed stopping rules have focused on quality with an implicit assumption that all cases have the same cost. This assumption is unlikely to be true, particularly when some cases will require more effort and, therefore, more costs than others. We propose a new rule that looks at both predicted costs and quality. This rule is tested experimentally against another rule that focuses on stopping cases that are expected to be difficult to recruit. The experiment was conducted on the 2020 data collection of the Health and Retirement Study (HRS). We test both Bayesian and non-Bayesian (maximum-likelihood or ML) versions of the rule. The Bayesian version of the prediction models uses historical data to establish prior information. The Bayesian version led to higher-quality data for roughly the same cost, while the ML version led to small reductions in quality with larger reductions in cost compared to the control rule. [ABSTRACT FROM AUTHOR]

In the United States, increasing access to the internet, the increasing costs of large-scale face-to-face data collections, and the general reluctance of the public to participate in intrusive in-person data collections all mean that new approaches to nationally representative surveys are urgently needed. The COVID-19 pandemic accelerated the need for faster, higher-quality alternatives to face-to-face data collection. These trends place a high priority on the evaluation of innovative web-based data collection methods that are convenient for the U.S. public and yield scientific information of high quality. The web mode is particularly appealing because it is relatively inexpensive, it is logistically flexible to implement, and it affords a high level of privacy and confidentiality when correctly implemented. With this study, we aimed to conduct a methodological evaluation of a sequential mixed-mode web/mail data collection protocol, including modular survey design concepts, which was implemented on a national probability sample in the U.S. in 2020–2021. We implemented randomized experiments to test theoretically-informed hypotheses that 1) the use of mail and increased incentives to follow up with households that did not respond to an invitation to complete a household screening questionnaire online would help to recruit different types of households; and 2) the use of modular survey design, which involves splitting a lengthy self-administered survey up into multiple parts that can be completed at a respondent's convenience, would improve survey completion rates. We find support for the use of mail and increased incentives to follow up with households that have not responded to a web-based screening questionnaire. We did not find support for the use of modular design in this context. Simple descriptive analyses also suggest that attempted telephone reminders may be helpful for the main survey. [ABSTRACT FROM AUTHOR]

To assess the elements necessary to be a successful learning community (ClinCalc) mentor to medical students from the mentee's perspective. Few such studies have utilized the in-depth and richness of detail obtained in qualitative studies. This qualitative study analyzed four focus group discussions lasting 45–90 min conducted at the University of Texas Southwestern Medical School, which has an established LC, in the year 2018. The groups included 14 pre-clerkship and 8 clerkship students. Investigators evaluated transcriptions of the focus group discussions using ATLAS.ti software. Three overarching categories of discussion emerged from the group discussions: (1) Relationship Competence, (2) Teaching Competence, and (3) Ethical and Compassionate Medical Practice Competence. Relationship Competence themes included "walk with me," relationship is most important, and one-on-one. Teaching Competence themes included above and beyond, recognize and address mentor limitations, and safe and enriching environment. Ethical and Compassionate Medical Practice Competence themes included ethical decision making and compassionate care for diverse patient populations. Mentees focused on various aspects of the mentor-mentee relationship as the single most essential competence. Themes mentees discussed as important qualities of a successful mentor may denote qualities to be prioritized in faculty development and mentor recruitment. Future studies could investigate how the LC environment informs former medical students and promotes patient outcomes. [ABSTRACT FROM AUTHOR]