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Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: The minimally invasive distal metatarsal osteotomy (MIDMO) is an increasingly popular technique for hallux valgus (HV) correction in the adult population. In juveniles, however, the use of minimally invasive methods to surgically resolve HV remains a comparatively new and under-reported concept. The primary objectives of this retrospective review are to provide radiographic findings of pediatric patients who underwent surgical correction of HV via the minimally invasive distal metatarsal osteotomy (MIDMO). Secondary objectives are the utilization of the mechanical axis of the first metatarsal to measure pre- and postoperative radiographic outcomes and time to osseous consolidation. Methods: A multi-center retrospective review was performed of two institution system’s records was conducted for consecutive patients who underwent surgical correction for HV between January 2012 and June 2022. Patients were included if they underwent HV correction using MIDMO, were aged < 18 years, had ≥ 3 months of clinical and radiographic follow-up, and had radiographs on file of both pre- and postoperative anteroposterior (AP) and lateral views. The first IMA (anatomic and mechanical axes), hallux abductus angle (HAA), distal metatarsal articular angle (DMAA), and tibial sesamoid position (TSP) were measured in pre- and postoperative AP and lateral views. A paired sample t-test was used to compare pre- and postoperative absolute radiographic measured angles. Results were considered statistically significant at the 5% (P < 0.05) level. Results: Forty-two feet amongst 30 patients met the inclusion criteria. Twenty seven were female (90%) and 3 of whom were male (10%). Temporary pin fixation (23.8%) or screw fixation (76.2%). Mean patient age was 15.2 years. Mean follow-up was 13.7 months. Mean time to osseous consolidation was 6.7 weeks. A statistically significant reduction was noted in all the radiographic values of every angle measured from preoperative to postoperative. The mean first anatomic IMA changed from 14.52° to 3.53° postoperatively and the first mechanical IMA changed from 14.24° to 4.64° postoperatively. The mean HAA was reduced from 32.98° to 12.83° postoperatively, the mean DMAA shifted from 12.40° to 2.93° postoperatively, and the mean TSP was revised from 3.60° preoperatively to 1.07° postoperatively. Conclusion: This is the first retrospective North American radiographic review in the known literature that evaluates short-term results of juvenile HV correction utilizing the MIDMO. Our results support the conclusion that the MIDMO is an effective method for pediatric patients with HV and provides statistically significant radiographic correction. Additionally, our results support the versatility of the mechanical axis in evaluating pre- and postoperative radiographic outcomes of the first IMA. We recommend future larger efforts with greater patient populations and longer follow-up times for further investigation.

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education.

ObjectiveCurrently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey.Study designWe recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18–44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes.ResultsA total of 500 respondents completed the survey. Three-quarters of respondents were

Summary: Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17–40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9–84·5%] vs. 70·2% [95% CI: 59·7–80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

ABSTRACT Cells increase their DNA content greater than the G2/M (DNA > 4n) phases along the path to cancer. The signals that support this increase in DNA content remain poorly understood. Cells infected with adenovirus (Ad) similarly develop DNA > 4n and share a need to bypass the DNA damage response (DDR) signals that trigger cell cycle arrest, and/or cell death. Ads with deletion in early region 1B55K (ΔE1B Ad) are oncolytic agents that are currently being explored for use in vaccine delivery. Interestingly, they promote higher levels of DNA > 4n than Ads that contain E1B55K. Existing in these and almost all Ads that are being explored for clinical use, is early region 4 (E4). The Ad E4 open reading frame 3 (E4orf3) is a viral oncogene that interferes with the ability of cells to respond to DNA damage by disrupting MRN complex formation. Our study reveals that E4orf3 is required for the enhanced fraction of ΔE1B Ad-infected cells with DNA > 4n. For that reason, we explored signaling events mediated by E4orf3. We found that in ΔE1B Ad-infected cells, E4orf3, as reported by others, isolates NBS1 in nuclear dots and tracks. This allows for elevated levels of phosphorylated ATM that is linked to transcriptionally active NF-κB. Pharmacological inhibition of NF-κB reduced the fraction of ΔE1B Ad-infected cells with DNA > 4n while pharmacological inhibition of ATM reduced the levels of nuclear NF-κB and the fraction of ΔE1B Ad-infected cells with DNA > 4n and increased the fraction of dead or dying cells with fragmented DNA. This ability of E4orf3 to disrupt MRN complex formation that allows cells to bypass the cell cycle, evade death, and accumulate DNA > 4n, may be linked to its oncogenic potential. IMPORTANCE Genome instability, a hallmark of cancer, exists as part of a cycle that leads to DNA damage and DNA > 4n that further enhances genome instability. Ad E4orf3 is a viral oncogene. Here, we describe E4orf3 mediated signaling events that support DNA > 4n in ΔE1B Ad-infected cells. These signaling events may be linked to the oncogenic potential of E4orf3 and may provide a basis for how some cells survive with DNA > 4n.

As demonstrated by the recent COVID pandemic, vaccines can reduce the burden arising from infectious agents. Adenoviruses (Ads) with deletion of the early region 1B55K (ΔE1B Ad) are currently being explored for use in vaccine delivery. ΔE1B Ads are different from Ads with deletions in early region 1 and early region 3 (ΔE1/E3) used in most Ad vaccine vectors in that they contain the Ad early region 1A (E1A), and therefore the ability to replicate. Common to almost all Ads that are being explored for clinical use is the Ad early region 4 (E4). Among the E4 genes is open reading frame 1 (E4orf1), which mediates signals through the PI3-kinase/Akt pathway that is known to modulate immune responses. This suggests that E4orf1 might also modulate immune responses, although it has remained unexplored in ΔE1B Ad. Here, we show that cells infected with an E1B55K and E4orf1-deleted (ΔE41) Ad exhibited reduced levels of phosphorylated Akt (Ser473 and Thr308)) and expressed different intrinsic innate immune cytokines from those induced in cells infected with an E4orf1-containing, ΔE1B parental Ad that exhibited elevated levels of phosphorylated Akt. Rhesus macaques immunized with a ΔE41 Ad that expressed rhFLSC (HIV-1BaL gp120 linked to rhesus CD4 D1 and D2), exhibited higher levels of rhFLSC-specific interferon γ-producing memory T-cells, higher titers of rhFLSC-specific IgG1 binding antibody in serum, and antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC) with greater killing capacity than the ΔE1B Ad. Therefore, E4orf1, perhaps by acting through the PI3-kinase/Akt pathway, limits intrinsic innate and system-wide adaptive immune responses that are important for improved ΔE1B Ad-based vaccines.

Objective: The objective was to evaluate the contraceptive effectiveness, safety, and acceptability of a novel vaginal pH regulator over seven cycles of use. Study design: A single-arm, open-label, phase 3 study was conducted across 112 sites in the United States in sexually active 18–35-year-old women at risk of pregnancy. Women administered the study treatment ≤1 h before each episode of intercourse. Women recorded use of study drug, coital information, and any symptoms experienced in electronic diaries. The primary outcome was the seven-cycle cumulative pregnancy rate as calculated using the Kaplan–Meier methodology; secondary outcomes included safety. Overall satisfaction was assessed via written questionnaires. Results: A total of 1384 women were enrolled in the study from July 2017 to November 2018. Mean age was 27.7 ± 4.4 years; most women were white (69.0%). The seven-cycle cumulative pregnancy percentage was 13.7% [95% confidence interval (CI): 10.0%–17.5%], meeting the prespecified primary endpoint of having the upper bound 95% CI ≤21%. Most common adverse events (AEs) occurring in ≥2% of women were vulvovaginal burning sensation, vulvovaginal pruritus, urinary tract infection, vulvovaginal pain, mycotic infection, bacterial vaginosis, and nasopharyngitis. Of 1330 women who used the study drug at least once, fewer than 2% of women discontinued due to any AEs, and 80% of women reported being “very satisfied” or “satisfied” with study treatment. Conclusions: In this phase 3 study, the novel vaginal pH regulator demonstrated 86.3% contraceptive effectiveness, was safe and well tolerated, and was highly acceptable. Implications: This novel vaginal pH regulator is a safe, nonhormonal, woman-controlled method of contraception that expands women's options.

Abstract Background Most tailed bacteriophages (phages) feature linear dsDNA genomes. Characterizing novel phages requires an understanding of complete genome sequences, including the definition of genome physical ends. Result We sequenced 48 Bacillus cereus phage isolates and analyzed Next-generation sequencing (NGS) data to resolve the genome configuration of these novel phages. Most assembled contigs featured reads that mapped to both contig ends and formed circularized contigs. Independent assemblies of 31 nearly identical I48-like Bacillus phage isolates allowed us to observe that the assembly programs tended to produce random cleavage on circularized contigs. However, currently available assemblers were not capable of reporting the underlying phage genome configuration from sequence data. To identify the genome configuration of sequenced phage in silico, a terminus prediction method was developed by means of ‘neighboring coverage ratios’ and ‘read edge frequencies’ from read alignment files. Termini were confirmed by primer walking and supported by phylogenetic inference of large DNA terminase protein sequences. Conclusions The Terminus package using phage NGS data along with the contig circularity could efficiently identify the proximal positions of phage genome terminus. Complete phage genome sequences allow a proposed characterization of the potential packaging mechanisms and more precise genome annotation.

There is an increasing number of culturally diverse individuals, particularly Asians, identified with autism spectrum disorder (ASD) in the United States. Nevertheless, research on culturally diverse caregivers, especially fathers, of children with ASD is scarce. Thus, this phenomenological study explored the essence of shared experiences of Korean fathers of children with ASD in the United States. Five fathers who have a child with ASD participated in a semistructured interview with a Korean-English bilingual researcher. Follow-up interviews and field notes were used for triangulation as a part of data analysis. The fathers' narratives regarding family characteristics, interactions, and functioning are discussed in alignment with the family systems theory. The findings provide recommendations for future practice and research.

This essay introduces a special issue of History of Political Economy titled "Local Entanglements in the History of Mathematical Economics." The articles in the special issue share a particular historiographical approach, characterized by the name of "local entanglements." The introduction defines the approach and explains why it can contribute in an original way to the history of economics. [ABSTRACT FROM AUTHOR]