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The genome sequences of thousands of bacteriophages have been determined and functions for many of the encoded genes have been assigned based on homology to characterized sequences. However, functions have not been assigned to more than two-thirds of the identified phage genes as they have no recognizable sequence features. Recent genome-wide overexpression screens have begun to identify bacteriophage genes that encode proteins that reduce or inhibit bacterial growth. This study describes the construction of a plasmid-based overexpression library of 76 genes encoded by Cluster K1 mycobacteriophage Amelie, which is genetically similar to cluster K phages Waterfoul and Hammy recently described in similar screens and closely related to phages that infect clinically important mycobacteria. Twenty-six out of the 76 genes evaluated in our screen, encompassing 34% of the genome, reduced growth of the host Mycobacterium smegmatis to various degrees. More than one-third of these 26 toxic genes have no known function, and 10 of the 26 genes almost completely abolished host growth upon overexpression. Notably, while several of the toxic genes identified in Amelie shared homologs with other Cluster K phages recently screened, this study uncovered 7 previously unknown gene families that exhibit cytotoxic properties, thereby broadening the repertoire of known phage-encoded growth inhibitors. This work, carried out under the HHMI-supported SEA-GENES project (Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists), underscores the importance of comprehensive overexpression screens in elucidating genome-wide patterns of phage gene function and novel interactions between phages and their hosts., Competing Interests: Conflicts of interest: The author(s) declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Research opportunities for undergraduate students are strongly advantageous, but implementation at a large scale presents numerous challenges. The enormous diversity of the bacteriophage population and a supportive programmatic structure provide opportunities to engage early-career undergraduates in phage discovery, genomics, and genetics. The Science Education Alliance (SEA) is an inclusive Research-Education Community (iREC) providing centralized programmatic support for students and faculty without prior experience in virology at institutions from community colleges to research-active universities to participate in two course-based projects, SEA-PHAGES (SEA Phage Hunters Advancing Genomic and Evolutionary Science) and SEA-GENES (SEA Gene-function Exploration by a Network of Emerging Scientists). Since 2008, the SEA has supported more than 50,000 undergraduate researchers who have isolated more than 23,000 bacteriophages of which more than 4,500 are fully sequenced and annotated. Students have functionally characterized hundreds of phage genes, and the phage collection has fueled the therapeutic use of phages for treatment of Mycobacterium infections. Participation in the SEA promotes student persistence in science education, and its inclusivity promotes a more equitable scientific community.

Importance: Higher lymphedema rates after axillary lymph node dissection (ALND) have been found in Black and Hispanic women; however, there is poor correlation between subjective symptoms, quality of life (QOL), and measured lymphedema. Additionally, racial and ethnic differences in QOL have been understudied., Objective: To evaluate the association of race and ethnicity with long-term QOL in patients with breast cancer treated with ALND., Design, Setting, and Participants: This cohort study enrolled women aged 18 years and older with breast cancer who underwent unilateral ALND at a tertiary cancer center between November 2016 and March 2020. Preoperatively and at 6-month intervals, arm volume was measured by perometer and QOL was assessed using the Upper Limb Lymphedema-27 (ULL-27) questionnaire, a validated tool for assessing lymphedema that evaluates how arm symptoms affect physical, psychological, and social functioning. Data were analyzed from November 2016 to October 2023., Exposures: Breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy., Main Outcomes and Measures: Scores in each domain of the ULL-27 were compared by race and ethnicity. Factors impacting QOL were identified using multivariable regression analyses., Results: The study included 281 women (median [IQR] age, 48 [41-58] years) with breast cancer who underwent unilateral ALND and had at least 6 months of follow-up. Of these, 30 patients (11%) self-identified as Asian individuals, 57 (20%) as Black individuals, 23 (8%) as Hispanic individuals, and 162 (58%) as White individuals; 9 individuals (3%) who did not identify as part of a particular group or who were missing race and ethnicity data were categorized as having unknown race and ethnicity. Median (IQR) follow-up was 2.97 (1.96-3.67) years. The overall 2-year lymphedema rate was 20% and was higher among Black (31%) and Hispanic (27%) women compared with Asian (15%) and White (17%) women (P = .04). Subjective arm swelling was more common among Asian (57%), Black (70%), and Hispanic (87%) women than White (44%) women (P < .001), and lower physical QOL scores were reported by racial and ethnic minority women at nearly every follow-up. For example, at 24 months, median QOL scores were 87, 79, and 80 for Asian, Black, and Hispanic women compared with 92 for White women (P = .003). On multivariable analysis, Asian race (β = -5.7; 95% CI, -9.5 to -1.8), Hispanic ethnicity (β = -10.0; 95% CI, -15.0 to -5.2), and having Medicaid (β = -5.4; 95% CI, -9.2 to -1.7) or Medicare insurance (β = -6.9; 95% CI, -10.0 to -3.4) were independently associated with worse physical QOL (all P < .001)., Conclusions and Relevance: Findings of this cohort study suggest that Asian, Black, and Hispanic women experience more subjective arm swelling after unilateral ALND for breast cancer compared with White women. Black and Hispanic women had higher rates of objective lymphedema than their White counterparts. Both minority status and public medical insurance were associated with worse physical QOL. Understanding disparities in QOL after ALND is an unmet need and may enable targeted interventions to improve QOL for these patients.

Over the past decade, thousands of bacteriophage genomes have been sequenced and annotated. A striking observation from this work is that known structural features and functions cannot be assigned for >65% of the encoded proteins. One approach to begin experimentally elucidating the function of these uncharacterized gene products is genome-wide screening to identify phage genes that confer phenotypes of interest like inhibition of host growth. This study describes the results of a screen evaluating the effects of overexpressing each gene encoded by the temperate Cluster F1 mycobacteriophage Girr on the growth of the host bacterium Mycobacterium smegmatis. Overexpression of 29 of the 102 Girr genes (~28% of the genome) resulted in mild to severe cytotoxicity. Of the 29 toxic genes described, 12 have no known function and are predominately small proteins of <125 amino acids. Overexpression of the majority of these 12 cytotoxic no known functions proteins resulted in moderate to severe growth reduction and represent novel antimicrobial products. The remaining 17 toxic genes have predicted functions, encoding products involved in phage structure, DNA replication/modification, DNA binding/gene regulation, or other enzymatic activity. Comparison of this dataset with prior genome-wide cytotoxicity screens of mycobacteriophages Waterfoul and Hammy reveals some common functional themes, though several of the predicted Girr functions associated with cytotoxicity in our report, including genes involved in lysogeny, have not been described previously. This study, completed as part of the HHMI-supported SEA-GENES project, highlights the power of parallel, genome-wide overexpression screens to identify novel interactions between phages and their hosts., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

The professional identity of scientists has historically been cultivated to value research over teaching, which can undermine initiatives that aim to reform science education. Course-Based Research Experiences (CRE) and the inclusive Research and Education Communities (iREC) are two successful and impactful reform efforts that integrate research and teaching. The aim of this study is to explicate the professional identity of instructors who implement a CRE within an established iREC and to explore how this identity contributes to the success of these programs. 97 CRE instructors from the Science Education Alliance (SEA) iREC participated in a 2-year, multi-stage, qualitative research project that involved weekly reflective journaling, autoethnographic description, small group evaluation and writing, and large-scale community checking. The resulting description of professional identity consisted of shared values (inclusivity, student success, community membership, ownership/agency, science, overcoming failure, and persistence), specified roles (mentor, advocate, scientist, educator, motivator, collaborator, community builder, learner, evaluator and project manager) and a stated sense of self (dedicated, resilient, pride in students, multiskilled, valued, community member, responsible and overworked). Analysis of individual reflective diary entries revealed how a professional identity underpinned and facilitated the ways in which faculty addressed challenges that arose and worked towards the success of every student. It is the self-concept of the professional identity of the instructor in the context of the CRE classroom that directed the extended commitment and effort that these instructors evidently put into their work with students, which facilitated student engagement, student persistence, and their collective scientific output. The study concludes that a professional identity of STEM faculty in the context of a CRE and iREC combines being a researcher and educator, and that this integrated identity is central for current initiatives aimed at transforming undergraduate STEM education.

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 modelling 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.

During infection, bacteriophages produce diverse gene products to overcome bacterial antiphage defenses, to outcompete other phages, and to take over cellular processes. Even in the best-studied model phages, the roles of most phage-encoded gene products are unknown, and the phage population represents a largely untapped reservoir of novel gene functions. Considering the sheer size of this population, experimental screening methods are needed to sort through the enormous collection of available sequences and identify gene products that can modulate bacterial behavior for downstream functional characterization. Here, we describe the construction of a plasmid-based overexpression library of 94 genes encoded by Hammy, a Cluster K mycobacteriophage closely related to those infecting clinically important mycobacteria. The arrayed library was systematically screened in a plate-based cytotoxicity assay, identifying a diverse set of 24 gene products (representing ∼25% of the Hammy genome) capable of inhibiting growth of the host bacterium Mycobacterium smegmatis. Half of these are related to growth inhibitors previously identified in related phage Waterfoul, supporting their functional conservation; the other genes represent novel additions to the list of known antimycobacterial growth inhibitors. This work, conducted as part of the HHMI-supported Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists (SEA-GENES) project, highlights the value of parallel, comprehensive overexpression screens in exploring genome-wide patterns of phage gene function and novel interactions between phages and their hosts., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: Sexual harassment is a known problem in surgical training and a focus of growing attention in recent years. However, the environments where sexual harassment in surgical training most commonly takes place are not yet described., Methods: An anonymous, voluntary, electronic survey was distributed to surgical trainees, and all programs nationally were invited to participate., Results: Sixteen general surgery training programs elected to participate, and the survey achieved a response rate of 30%. 48.9% of respondents reported experiencing sexual harassment. The most common location for harassment was in the operating room (OR) (74% of harassed respondents). The second most common location for harassment was the wards (67.4% of harassed respondents). In the OR, attendings and nurses were the most common harassers. The most common harassment in the OR was being called a sexist slur or intimate nickname., Discussion: Surgical trainees report that the OR was the most common location for trainee harassment. Given that harassment is most commonly perpetrated by both attendings and nurses, harassment in surgical training may not entirely be due to hierarchies but may also be attributed to a flawed and permissive OR culture. Surgical training programs should vigilantly eliminate the circumstances that permit sexual harassment in the OR., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ancillary therapies with rehabilitative, palliative, and survivorship specialists mitigate adverse effects of breast cancer surgery. Existing data suggest that patients from disadvantaged backgrounds may be less likely to receive these services. This study aimed to assess variations in ancillary provider referrals and patient visits at a high-volume urban cancer center., Methods: Electronic health records of breast cancer surgical patients at the Yale-New Haven Health System between 2010 and 2017 were reviewed. The primary end points were postoperative referral to ancillary service providers and patient use of ancillary services (defined as attending ≥ 1 consultation). Associations between end points and demographic/disease variables were identified in uni- and multivariable logistic regression analyses., Results: The study identified 5496 patients: 2288 patients (41.6%) referred to ancillary services and 1572 patients (28.6%) who attended one or more consultations. Referrals were highest among the patients with Hispanic (57.5%) or black (54.9%) ancestry, no health insurance (57.6%), lowest percentage of high school degrees for the zip code area (50.5%), and poorest median income bracket (50.7%). Associations remained significant in the multivariable analysis (p < 0.05). Minority race remained associated with referrals in analyses of each ancillary service individually. Visits to ancillary specialists were greatest among the patients with private insurance (70.7%), highest percentage of high school degrees (72.8%), highest median household income (72.2%), and Hispanic ethnicity (73.5%). Highest median household income (odds ratio [OR] 1.45; p = 0.02) and Hispanic ethnicity (OR, 1.50; p = 0.05) remained associated in the multivariable analysis., Conclusions: In a well-resourced health system serving a demographically diverse population, traditional markers of poor health care access were associated with referral for ancillary treatment after breast cancer surgery but not with utilization of ancillary treatment. Health care access remains a critical barrier to adjunctive therapies that target postoperative morbidity and elevate quality of life., (© 2023. Society of Surgical Oncology.)

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.

Bacteriophages represent an enormous reservoir of novel genes, many of which are unrelated to existing entries in public databases and cannot be assigned a predicted function. Characterization of these genes can provide important insights into the intricacies of phage-host interactions and may offer new strategies to manipulate bacterial growth and behavior. Overexpression is a useful tool in the study of gene-mediated effects, and we describe here the construction of a plasmid-based overexpression library of a complete set of genes for Waterfoul, a mycobacteriophage closely related to those infecting clinically important strains of Mycobacterium tuberculosis and/or Mycobacterium abscessus. The arrayed Waterfoul gene library was systematically screened in a plate-based cytotoxicity assay, identifying a diverse set of 32 Waterfoul gene products capable of inhibiting the growth of the host Mycobacterium smegmatis and providing a first look at the frequency and distribution of cytotoxic products encoded within a single mycobacteriophage genome. Several of these Waterfoul gene products were observed to confer potent anti-mycobacterial effects, making them interesting candidates for follow-up mechanistic studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Bacteriophage EmiRose is a siphovirus infecting Corynebacterium flavescens. The EmiRose genome is 37,431 bp long and composed of 47 protein-coding genes. Based on gene content similarity, EmiRose is not closely related to any previously sequenced bacteriophages in the actinobacteriophage database to date, including other corynebacteriophages. EmiRose is classified as a singleton.

Bacteriophage EasyJones is a myovirus infecting Mycobacterium smegmatis mc 2 155, with a genome length and gene content similar to those of phages grouped in subcluster C1. Interestingly, EasyJones contains a gene found in a subset of C1 genomes that is similar to the well-characterized immunity repressor of subcluster A1 mycobacteriophage Bxb1.

Background: Numerous studies have evaluated the effect of post-mastectomy radiotherapy (PMRT) on autologous breast reconstruction, but the variability of PMRT regimens and inadequate controls have made results difficult to interpret. Therefore, in this study, irradiated free-flaps are compared to non-irradiated internal controls in patients who underwent immediate bilateral reconstruction followed by unilateral PMRT to better delineate the effect of PMRT. The role of regional nodal irradiation (RNI) is also specifically assessed., Methods: Appropriate patients were identified through retrospective review. Complications such as fat necrosis, fibrosis, infection, delayed healing, and flap loss, as well as revision surgeries, among the irradiated free-flaps were compared to those on the contralateral non-irradiated side. Additional analyses were performed to evaluate the effect of patient demographics and treatment characteristics, such as RNI, on complications involving the irradiated free-flaps., Results: Seventy-three women were included. There was no significant difference between complication rates for the irradiated and non-irradiated free-flaps (39.7% vs. 38.4%, p = .78), although irradiated free-flaps were more likely to have fibrosis (17.0% vs. 0.0%; p < .0001) and multiple complications (9.6% vs. 0.0%; p = .02). Both groups underwent a similar number of revision surgeries (42.5% vs. 41.1%; p = .29). Looking at the irradiated free-flaps, internal mammary node (IMN) irradiation was the only factor predictive of complications (IRR 3.80, CI 1.32-10.97; p = .01)., Conclusions: PMRT may contribute to free-flap fibrosis, but does not appear to affect the overall risk of complications or revision surgeries. However, additional counseling is warranted if IMN irradiation is likely, as it is potentially associated with increased complications., (© 2021 Wiley Periodicals LLC.)

Background: Angiosarcoma of the breast is rare and aggressive. It can occur as a de novo tumor or secondary to breast cancer treatment. The purpose of this study is to analyze differences between patients with primary and secondary angiosarcoma of the breast and investigate potential risk factors for its development., Patients and Methods: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute database was queried to identify patients with angiosarcoma of the breast, trunk, shoulder, and upper arm. The population-based incidence was analyzed. Primary and secondary angiosarcoma cases were identified and compared. Breast cancer characteristics of secondary angiosarcoma patients were compared with all breast cancer patients in the database who did not develop angiosarcoma., Results: Overall, 904 patients were included, and 65.4% were secondary angiosarcomas. These patients had worse survival, were older, more likely to be White, more likely to have regionally advanced disease, and had angiosarcoma tumors of higher pathologic grade. Independent factors associated with development of secondary angiosarcoma among breast cancer patients included White race, older age, invasive tumor, lymph node removal, lumpectomy, radiation treatment, and left-sided tumor. Although the mean time to develop angiosarcoma after breast cancer diagnosis was 8.2 years, the risk continues to increase up to 30 years after breast cancer treatment., Conclusion: Angiosarcoma is rare but increasing in incidence. Secondary angiosarcomas are more common and exhibit more aggressive behavior. Several factors for angiosarcoma after breast cancer treatment could be identified, which may help us counsel and identify patients at risk., (© 2021. Society of Surgical Oncology.)

Objective: Fatigued driving is a known contributor to adverse motor vehicle events (AMVEs), defined as crashes and near misses. Surgical trainees work long and irregular hours; the safety of work-related driving since the introduction of work hour regulations has not yet been studied in this population. We aimed to assess the impact of fatigue on driving safety and explore perceptions of a funded rideshare program., Design: An electronic survey was delivered and inquired in retrospective fashion about fatigue and sleepiness while driving, occurrences of AMVEs, and projected use of a funded rideshare program as a potential solution to unsafe driving. Chi-square testing determined categorical differences between response choices., Setting: Yale University School of Medicine, Department of Surgery, New Haven, CT-a general surgery program with 4 urban clinical sites positioned along a roughly twenty mile stretch of interstate highway in Southeastern Connecticut., Participants: General Surgery residents at the Yale University School of Medicine., Results: Of 58 respondents (81% response rate), 97% reported that fatigue compromised their safety while driving to or from work. Eighty-three percent reported falling nearly or completely asleep, and 22% reported AMVEs during work-related driving. Junior residents were more likely than Seniors to drive fatigued on a daily-to-weekly basis (69% vs 47%, p = 0.02) and twice as likely to fall asleep on a weekly-to-monthly basis (67% vs 33%, p = 0.02). Despite this, only 7% of residents had ever hired a ride service when fatigued, though 88%, would use a free rideshare service if provided., Conclusions: Work-related fatigue impairs the driving safety of nearly all residents, contributing to frequent AMVEs. Currently, few residents hire rideshare services. Eliminating the cost barrier by funding a rideshare and encouraging its routine use may protect surgical trainees and other drivers., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: In 2017 the ACGME enacted new regulations requiring sponsoring institutions to ensure "safe transportation options for residents who may be too fatigued to safely return home." We investigate here the impact of a pilot "Safe Ride" program designed to mitigate the risks of fatigued driving., Methods: During a 2-month pilot period at a single university-affiliated general surgery residency with four urban clinical sites, all residents (n = 72) were encouraged to hire a rideshare (e.g., Uber, Lyft) to and from 24-h clinical shifts if they felt too fatigued to drive safely. The cost of the rideshare was fully reimbursed to the resident. The impact of this intervention was evaluated using utilization data and a post-intervention resident survey., Results: A total of 16.6% of trainees utilized a rideshare at least one time. Sixty-three post-call rides were taken, predominantly by junior residents (92.4%) and for commutes greater than 15 miles (91%). The cost for the 60-day pilot was $3030. Comparing pre-intervention to post-intervention data, there was a significant improvement in the reported frequency of falling asleep or nearly asleep while driving (P < 0.001). Trainees nearly unanimously (98%) supported efforts to make the program permanent., Discussion: Driving while fatigued is common among surgical residents, with increased risk among junior residents, during longer commutes and following longer shifts. A reimbursed rideshare program effectively targets these risk factors and was associated with a significant decrease in rates of self-reported fatigued driving. Future efforts should focus on strategies to promote use of reimbursed rideshare programs while remaining cost efficient., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Timing of autologous reconstruction relative to postmastectomy radiation therapy (PMRT) is debated. Benefits of immediate reconstruction must be weighed against a possibly heightened risk of complications from flap irradiation. We reviewed flap outcomes after single operation plus PMRT in a large institutional cohort., Methods: Medical records were reviewed for women who underwent simultaneous mastectomy-autologous reconstruction with PMRT from 2007 to 2016. Primary endpoints were rates and types of radiation-related flap complications and reoperations, whose predictors were assessed by multivariable analysis. A p value < 0.10 was deemed significant to avoid type II error. Non-parametric logistic regression generated a model of PMRT timing associated with probabilities of complications and reoperations., Results: One-hundred and thirty women underwent 208 mastectomy reconstruction operations, with a median follow up of 35.1 months (interquartile range 23.6-56.5). Forty-seven (36.2%) women experienced radiation-related complications, commonly fat necrosis (44.1%) and chest wall asymmetry (28.8%). Complications were higher among women who received PMRT < 3 months after surgery (46.8% for < 3 months vs. 29.3% for ≥ 3 months; p = 0.06), most of whom received neoadjuvant chemotherapy, and among women treated with internal mammary nodal (IMN) radiation (65.2% vs. 26.4%; p < 0.01); IMN radiation remained strongly associated in multivariable analysis (odds ratio [OR] 5.24; p < 0.01). Thirty-two (24.6%) women underwent 70 reoperations, commonly fat grafting (51.9%) and fat necrosis excision (17.1%). Reoperations were higher among women who received PMRT < 3 months after surgery (48.9 for < 3 months vs. 36.6 for ≥ 3 months; p = 0.19), which was significantly associated in multivariable analysis (OR 0.42; p = 0.08 for ≥ 3 months). The probabilities of complications and reoperations were lowest when PMRT was administered ≥ 3 months after surgery., Conclusions: Among a large institutional cohort, immediate autologous reconstruction was associated with similar rates of adverse flap outcomes as historically reported alternatively sequenced protocols. IMN radiation increased risk, while PMRT ≥ 3 months after surgery decreased risk. Additional studies are needed to elaborate the impact of IMN radiation and early PMRT in immediate versus delayed autologous reconstruction.

Importance: The expansion of Medicaid sought to fill gaps in insurance coverage among low-income Americans. Although coverage has improved, little is known about the relationship between Medicaid expansion and breast cancer stage at diagnosis., Objective: To review the association of Medicaid expansion with breast cancer stage at diagnosis and the disparities associated with insurance status, age, and race/ethnicity., Design, Setting, and Participants: This cohort study used data from the National Cancer Database to characterize the relationship between breast cancer stage and race/ethnicity, age, and insurance status. Data from 2007 to 2016 were obtained, and breast cancer stage trends were assessed. Additionally, preexpansion years (2012-2013) were compared with postexpansion years (2015-2016) to assess Medicaid expansion in 2014. Data were analyzed from August 12, 2019, to January 19, 2020. The cohort included a total of 1 796 902 patients with primary breast cancer who had private insurance, Medicare, or Medicaid or were uninsured across 45 states., Main Outcomes and Measures: Percent change of uninsured patients with breast cancer and stage at diagnosis, stratified by insurance status, race/ethnicity, age, and state., Results: This study included a total of 1 796 902 women. Between 2012 and 2016, 71 235 (4.0%) were uninsured or had Medicaid. Among all races/ethnicities, in expansion states, there was a reduction in uninsured patients from 22.6% (4771 of 21 127) to 13.5% (2999 of 22 150) (P < .001), and in nonexpansion states, there was a reduction from 36.5% (5431 of 14 870) to 35.6% (4663 of 13 088) (P = .12). Across all races, there was a reduction in advanced-stage disease from 21.8% (4603 of 21 127) to 19.3% (4280 of 22 150) (P < .001) in expansion states compared with 24.2% (3604 of 14 870) to 23.5% (3072 of 13 088) (P = .14) in nonexpansion states. In African American patients, incidence of advanced disease decreased from 24.6% (1017 of 4136) to 21.6% (920 of 4259) (P < .001) in expansion states and remained at approximately 27% (27.4% [1220 of 4453] to 27.5% [1078 of 3924]; P = .94) in nonexpansion states. Further analysis suggested that the improvement was associated with a reduction in stage 3 diagnoses., Conclusions and Relevance: In this cohort study, expansion of Medicaid was associated with a reduced number of uninsured patients and a reduced incidence of advanced-stage breast cancer. African American patients and patients younger than 50 years experienced particular benefit. These data suggest that increasing access to health care resources may alter the distribution of breast cancer stage at diagnosis.

Objective: Physician burnout, including surgical trainees, is multidimensional. Input variables used to predict burnout include grit, exhaustion, and financial stress. Each instrument has intrinsic limitations of scope and strength. We hypothesize that bioinformatics methods borrowed from oncogenetics may allow meta-analysis of existing predictive tools to improve identification of subpopulations at highest risk of burnout., Design: A composite survey was created using widely accepted instruments: demographic factors, burnout using the Single-Item Maslach Burnout Inventory Emotional Exhaustion Measure, grit using the Duckworth Grit Scale, occupational fatigue using the Occupational Fatigue Exhaustion/Recovery Scale, financial well-being, perceptions of physician leadership, and attitudes towards robotic surgery. Surveys were analyzed using k-means analysis and supervised/unsupervised clustering., Setting: Yale General Surgery Residency., Participants: Survey participants consisted of Yale General Surgery residents. Of 70 residents, 53 responded (75.7%). Males comprised 57.1% and each postgraduate year had majority representation, 68.8% to 100%., Results: Unsupervised hierarchical clustering showed heterogeneous resident answer patterns and suggested clusters of responders. To define groups of dissimilar responders, we performed k-means clustering, testing 15 iterations with 50 attempts. The analysis revealed 3 discrete clusters of responders with differential risk for burnout (p = 0.021). The highest risk group demonstrated the lowest grit score, low interest in innovation and leadership, higher financial stress, and concordantly, the highest rates of anxiety, dread, and self-reported burnout. (p = 0.0004; 0.0014; 0.1217; 0.0625; 0.021; 0.0011; 0.0224) CONCLUSIONS: The limited scope of common tools aiming to predict burnout constrains their utility. The machine-learning technique of cluster analysis organizes compound data to describe complex outcomes such as oncologic risks. We apply this analysis technique to create a composite predictor of burnout among surgical residents. Our method determines subgroups of residents sharing unique traits predictive of burnout. Residencies can use this tool to allocate resources to best support resident well-being., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the occurrence, nature, and reporting of sexual harassment in surgical training and to understand why surgical trainees who experience harassment might not report it. This information will inform ways to overcome barriers to reporting sexual harassment., Summary/ Background Data: Sexual harassment in the workplace is a known phenomenon with reports of high frequency in the medical field. Aspects of surgical training leave trainees especially vulnerable to harassing behavior. The characteristics of sexual harassment and reasons for its underreporting have yet to be studied on the national level in this population., Methods: An electronic anonymous survey was distributed to general surgery trainees in participating program; all general surgery training programs nationally were invited to participate., Results: Sixteen general surgery training programs participated, yielding 270 completed surveys (response rate of 30%). Overall, 48.9% of all respondents and 70.8% of female respondents experienced at least 1 form of sexual harassment during their training. Of the respondents who experienced sexual harassment, 7.6% reported the incident. The most common cited reasons for nonreporting were believing that the action was harmless (62.1%) and believing reporting would be a waste of time (47.7%)., Conclusion: Sexual harassment occurs in surgical training and is rarely reported. Many residents who are harassed question if the behavior they experienced was harassment or feel that reporting would be ineffectual-leading to frequent nonreporting. Surgical training programs should provide all-level education on sexual harassment and delineate the best mechanism for resident reporting of sexual harassment.

Background: The only possibility for cure in patients with colon adenocarcinoma (CAC) with isolated liver metastases (ILM) is resection of both primary and metastatic tumors. Little is known about the implication of the sequence in which a colectomy and hepatectomy are performed on outcomes. This study analyzes whether resection sequence impacts clinical outcomes., Methods: The National Cancer Database was queried for CAC cases with hepatic metastases from 2010-2015 with exclusion of extrahepatic metastases. We compared patients treated with a liver-first approach (LFA) to those treated with a colectomy-first or simultaneous approach using Kaplan Meier and multivariable Cox proportional hazards analysis., Results: In 21,788 CAC patients identified, the LFA was uncommon (2%), but was associated with higher rates of completion resection of remaining tumor (41% vs . 22%, P<0.001). Patients selected for LFA were younger, less comorbid, and more commonly received upfront chemotherapy (P<0.05). The LFA was associated with increased median survival [34 months, 95% CI (30.5-39.6 months) vs . 24 months, 95% CI (23.7-24.6 months), logrank P<0.001] and decreased risk of death [HR 0.783; 95% CI (0.67-0.89), P=0.001]., Conclusions: The LFA to CAC with synchronous ILM is uncommon but is associated with greater likelihood of receiving chemotherapy prior to surgery and increased survival in selected candidates., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Classification of lung adenocarcinoma (LUAD) currently relies on the TNM pathological staging system, which cannot fully account for the variability in postsurgery overall survival (OS). Despite the advances in immunotherapy and increased appreciation of the involvement of cancer immune microenvironment (IME) in cancer progression, the contribution of IME to postsurgery LUAD prognosis is not well understood., Methods: We digitally inferred the contribution of 22 immune cell types or activation states to the tumor IME using CIBERSORT (Celltype Identification By Estimating Relative Subsets Of RNA Transcripts) analysis in an exploratory metadataset of 581 patients with early-stage LUAD. Patients were arranged based on similarity in IME using k-means clustering. Relationship to postsurgical OS was tested in univariable and multivariable models using Kaplan-Meier analysis and Cox proportional hazards modeling, respectively. To confirm survival relationships, a support vector machine classifier was constructed from a comparison of low-risk and high-risk IME groups. The classifier was applied to a the Cancer Genome Atlas LUAD validation dataset of 394 patients., Results: Patients with an inferred IME enriched in resting mast cells and depleted of macrophages represented a low-clinical-risk group in both exploratory and validation cohorts., Conclusions: Variability in the digitally inferred composition of the tumor IME contributes to heterogeneity in postsurgical OS. Our data suggest that low inferred macrophage content and inferred resting activation state of intratumor mast cells are associated with improved clinical outcome. Computational inference can be used to define LUAD risk groups and help guide clinical decision making., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence and worse outcomes among black patients than white patients, potentially owing to a combination of socioeconomic, biological, and treatment differences. The role that these differences play remains unknown., Objectives: To determine the level of survival disparity between black and white patients in a modern PDAC cohort and whether treatment inequity is associated with such a disparity., Design, Setting, and Participants: This cohort study used data on 278 936 patients with PDAC with database-defined race from the National Cancer Database from January 1, 2004, to December 31, 2015. The median follow-up for censored patients was 24 months. The National Cancer Database, comprising academic and community facilities, includes about 70% of new cancer diagnoses in the United States. Race-stratified receipt of therapy was the primary variable of interest. Multivariable analyses included additional demographic and clinical parameters. Data analysis was initially completed on November 30, 2018, and revised data analysis was completed on June 27, 2019., Main Outcomes and Measures: Overall survival was the primary outcome, analyzed with Kaplan-Meier and multivariable Cox proportional hazards regression modeling., Results: The cohort included 278 936 patients (137 121 women and 141 815 men; mean [SD] age, 68.72 [11.57] years); after excluding patients from other racial categories, 243 820 of the 278 936 patients (87.4%) were white and 35 116 of the 278 936 patients (12.6%) were black. Unadjusted median overall survival was longer for white patients than for black patients (6.6 vs 6.0 months; P < .001). Black patients presented at younger ages than white patients (15 819 of 35 116 [45.0%] vs 83 846 of 243 820 [34.4%] younger than 65 years; P < .001) and with more advanced disease (20 853 of 31 600 [66.0%] vs 135 317 of 220 224 [61.4%] with stage III or IV disease; P < .001). Black patients received fewer surgical procedures than white patients for potentially resectable stage II disease (4226 of 8097 [52.2%] vs 39 214 of 65 124 [60.2%]; P < .001) and slightly less chemotherapy for advanced disease (2756 of 4067 [67.8%] vs 17 296 of 25 227 [68.6%] for stage III disease [P = .001]; 8208 of 16 104 [51.0%] vs 58 603 of 105 616 [55.5%] for stage IV disease [P < .001]). Decreased survival for black patients persisted in multivariable modeling controlled for sociodemographic parameters (hazard ratio, 1.04 [95% CI, 1.02-1.05]). Conversely, modeling that controlled specifically for clinical parameters such as disease stage and treatment revealed a modest survival advantage (hazard ratio, 0.94 [95% CI, 0.93-0.96]) among black patients. Resection was the factor most strongly associated with overall survival (hazard ratio, 0.39 [95% CI, 0.38-0.39])., Conclusions and Relevance: Black patients with PDAC present at younger ages and with more advanced disease than white patients, suggesting that differences in tumor biology may exist. Black patients receive less treatment stage for stage and fewer surgical procedures for resectable cancers than white patients; these findings may be only partly associated with socioeconomic differences. When disease stage and treatment were controlled for, black patients had no decrease in survival.

Background: Surgical management of appendiceal carcinoid tumors is heavily debated, despite National Comprehensive Cancer Network guidelines recommending aggressive resection of tumors >2 cm. We investigated national practice patterns and the predictors and impact of guideline non-adherence., Study Design: The National Cancer Database was queried for cases of appendiceal carcinoids diagnosed from 2004 to 2015 treated with either appendectomy or hemicolectomy. Multivariable logistic regression, adjusted for demographic and clinical factors, identified associations with the procedure type among patients stratified by tumor size ≤2 cm and >2 cm. Cox Proportional Hazards then identified associations with overall survival among stratified patient groups., Results: Of 3,198 cases of appendiceal carcinoids, 1,893 appendectomies and 1,305 hemicolectomies were identified. Contrary to National Comprehensive Cancer Network guidelines, 32.4% of tumors ≤2 cm were treated with hemicolectomy and 31.3% of tumors >2 cm were treated with definitive appendectomy. Hemicolectomy for small tumors was associated with age 65 years and older (odds ratio [OR] 2.4; 95% CI 1.7 to 3.3; reference group age 18 to 39 years), history of malignancy (OR 2.0; 95% CI 1.6 to 2.6), tumor size 1.1 to 2 cm (OR 2.8; 95% CI 2.3 to 3.4; reference group size ≤1 cm), and lymphovascular invasion (OR 2.2; 95% CI 1.6 to 3.2); appendectomy for large tumors was associated with age 65 years and older only (OR 2.2; 95% CI 1.1 to 4.2). Procedure type was not associated with survival for small or large tumors (hazard ratio 1.0; 95% CI 0.7 to 1.4 and hazard ratio 1.1; 95% CI 0.6 to 2.0, respectively)., Conclusions: Despite well-known size-based treatment guidelines for appendiceal carcinoids, one-third of patients in the US undergo hemicolectomy for small tumors and appendectomy for large tumors. Guideline non-adherence, however, is not associated with overall survival. Reasons for these practice patterns should be explored, and guidelines revisited., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

: Background : Despite screening mammography, the incidence of Stage IV breast cancer (BC) at diagnosis has not decreased over the past four decades. We previously found that many BCs are small due to favorable biology rather than early detection. This study compared the biology of Stage IV cancers with that of small cancers typically found by screening. Methods : Trends in the incidence of localized, regional, and distant female BC were compared using SEER*Stat. The National Cancer Database (NCDB) was then queried for invasive cancers from 2010 to 2015, and patient/disease variables were compared across stages. Biological variables including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), grade, and lymphovascular invasion were sorted into 48 combinations, from which three biological subtypes emerged: indolent, intermediate, and aggressive. The distributions of the subtypes were compared across disease stages. Multivariable regression assessed the association between Stage IV disease and biology. Results : SEER*Stat confirmed that the incidence of distant BC increased between 1973 and 2015 (annual percent change [APC] = 0.46). NCDB data on roughly 993,000 individuals showed that Stage IV disease at presentation is more common in young, black, uninsured women with low income/education and large, biologically aggressive tumors. The distribution of tumor biology varied by stage, with Stage IV disease including 37.6% aggressive and 6.0% indolent tumors, versus sub-centimeter Stage I disease that included 5.1% aggressive and 40.6% indolent tumors ( p < 0.001). The odds of Stage IV disease presentation more than tripled for patients with aggressive tumors (OR3.2, 95% CI 3.0⁻3.5). Conclusions : Stage I and Stage IV breast cancers represent very different populations of biologic tumor types. This may explain why the incidence of Stage IV cancer has not decreased with screening., Competing Interests: The authors declare no conflict of interest.

Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the lack of genetic assays for detecting their conversion to an aggregated prion conformation. Here we describe a bacteria - based genetic assay that distinguishes cells carrying a model yeast prion protein in its nonprion and prion forms. We then use this assay to investigate the prion-forming potential of single-stranded DNA-binding protein (SSB) of Campylobacter hominis Our findings indicate that SSB possesses a prion-forming domain that can transition between nonprion and prion conformations. Furthermore, we show that bacterial cells can propagate the prion form over 100 generations in a manner that depends on the disaggregase ClpB. The bacteria-based genetic tool we present may facilitate the investigation of prion-like phenomena in all domains of life., Competing Interests: The authors declare no conflict of interest.

Background: The benefits of palliative care (PC) in critical illness are validated across a range of diseases, yet it remains underutilized in surgical patients. This study analyzed patient and hospital factors predictive of PC utilization for elderly patients with colorectal cancer (CRC) requiring emergent surgery., Methods: The National Inpatient Sample was queried for patients aged ≥ 65 years admitted emergently with CRC from 2009 to 2014. Patients undergoing colectomy, enterectomy, or ostomy formation were included and stratified according to documentation of PC consultation during admission. Chi-squared testing identified unadjusted group differences, and multivariable logistic regression identified predictors of PC., Results: Of 86,573 discharges meeting inclusion criteria, only 3598 (4.2%) had PC consultation. Colectomy (86.6%) and ostomy formation (30.4%) accounted for the operative majority. PC frequency increased over time (2.9% in 2009 to 6.2% in 2014, P < 0.001) and was nearly twice as likely to occur in the West compared with the Northeast (5.7 vs. 3.3%, P < 0.001) and in not-for-profit compared with proprietary hospitals (4.5 vs. 2.3%, P < 0.001). PC patients were more likely to have metastases (60.1 vs. 39.9%, P < 0.001) and die during admission (41.5 vs. 6.4%, P < 0.001). On multivariable logistic regression, PC predictors (P < 0.05) included region outside the Northeast, increasing age, more recent year, and metastatic disease., Conclusions: In the USA, PC consultation for geriatric patients with surgically managed complicated CRC is low. Regional variation appears to play an important role. With mounting evidence that PC improves quality of life and outcomes, understanding the barriers associated with its provision to surgical patients is paramount.

Background: Colorectal cancer (CRC) incidence is rising in the young, yet the age of those affected is not clearly defined. In this study, we identify such cohorts and define clinicopathological features of early-onset colon and rectal cancers. Methods: The Surveillance, Epidemiology and End Results Program (SEER) database was queried to compare clinicopathological characteristics of colon and rectal cancers diagnosed during 1973-1995 with those diagnosed during 1995-2014. Results: We identified 430,886 patients with colon and rectal cancers. From 1973-1995 to 1995-2014, colon cancer incidence increased in patients aged 20-44 years, while rectal cancer incidence increased in patients aged ≤54 years. The percent change of cancer incidence was greatest for rectal cancer with a 41.5% (95% confidence interval (CI): 37.4-45.8%) increase compared to a 9.8% (CI: 6.2-13.6%) increase in colon cancer. Colon cancer has increased in tumors located in ascending, sigmoid, and rectosigmoid locations. Adenocarcinoma histology has increased in both colon and rectal cancers ( P < 0.01), but mucinous and signet ring cell subtypes have not increased ( P = 0.13 and 0.08, respectively). Incidence increases were race-specific, with rectal cancer seeing similar rises in white (38.4%, CI: 33.8-43.1%) and black populations (38.0%, CI: 26.2-51.2%), while colon cancer as a whole saw a rise in white (11.5%, CI: 7.2-15.9%) but not black populations (-6.8%, CI: -14.6-1.9%). Conclusions: Our study underscores the existence of key differences between early-onset colon (20-44 years) and rectal cancers (≤54 years) and provides evidence-based inclusion criteria for future investigations. We recommend that future research of CRC in the young should avoid investigating these cases as a single entity.

Self-assembly of proteins into filaments, such as actin and tubulin filaments, underlies essential cellular processes in all three domains of life. The early emergence of filaments in evolutionary history suggests that filament genesis might be a robust process. Here we describe the fortuitous construction of GFP fusion proteins that self-assemble as fluorescent polar filaments in Escherichia coli. Filament formation is achieved by appending as few as 12 residues to GFP. Crystal structures reveal that each protomer donates an appendage to fill a groove between the two following protomers along the filament. This exchange of appendages resembles runaway domain swapping but is distinguished by higher efficiency because monomers cannot competitively bind their own appendages. Ample evidence for this 'runaway domain coupling' mechanism in nature suggests it could facilitate the evolutionary pathway from globular protein to polar filament, requiring a minimal extension of protein sequence and no substantial refolding.

Background: The prognosis for patients with diffuse malignant peritoneal mesothelioma has dramatically improved with cytoreductive surgery and intraperitoneal chemotherapy. Little is known about disease recurrence after treatment. We analyzed the time to and predictors of recurrence in a large cohort of optimally treated patients., Methods: We examined 113 patients completing a two-stage cytoreduction and intraperitoneal chemotherapy protocol. All patients achieved optimal surgical resection with completeness of cytoreduction (CC) score ≤ 1 and were divided into two groups based on absence (Group A) or presence (Group B) of gross disease at the outset of the second operation. Predictors of disease recurrence and recurrence-free survival (RFS) were determined using Cox proportional hazard regression modeling, and estimates were obtained by using the Kaplan-Meier method., Results: Forty-six percent of patients had no gross evidence of disease at the second operation; the remaining 54% were cytoreduced to CC ≤ 1 (Group B). Forty-two percent of patients developed disease recurrence with a median recurrence-free survival of 38.5 months for the cohort; 79% of these received a form of iterative treatment. There was no statistically significant difference in recurrence-free survival between Group A (median RFS: 44.6 months) and B (median RFS: 35.5 months) (log-rank test, p = 0.06). Additionally, the only variable significantly associated with RFS was male gender (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.16-3.38)., Conclusions: Absence of gross disease at the second operation was not statistically protective against recurrence compared with presence of quantifiable residual disease (Group B) that was effectively cytoreduced. Long-term disease surveillance is recommended, because recurrence continues years after treatment. Where a question of recurrence arises on surveillance, males may benefit from a higher degree of suspicion.

The toxin components of toxin-antitoxin modules, found in bacterial plasmids, phages, and chromosomes, typically target a single macromolecule to interfere with an essential cellular process. An apparent exception is the chromosomally encoded toxin component of the E. coli CbtA/CbeA toxin-antitoxin module, which can inhibit both cell division and cell elongation. A small protein of only 124 amino acids, CbtA, was previously proposed to interact with both FtsZ, a tubulin homolog that is essential for cell division, and MreB, an actin homolog that is essential for cell elongation. However, whether or not the toxic effects of CbtA are due to direct interactions with these predicted targets is not known. Here, we genetically separate the effects of CbtA on cell elongation and cell division, showing that CbtA interacts directly and independently with FtsZ and MreB. Using complementary genetic approaches, we identify the functionally relevant target surfaces on FtsZ and MreB, revealing that in both cases, CbtA binds to surfaces involved in essential cytoskeletal filament architecture. We show further that each interaction contributes independently to CbtA-mediated toxicity and that disruption of both interactions is required to alleviate the observed toxicity. Although several other protein modulators are known to target FtsZ, the CbtA-interacting surface we identify represents a novel inhibitory target. Our findings establish CbtA as a dual function toxin that inhibits both cell division and cell elongation via direct and independent interactions with FtsZ and MreB.

Objective: The objective of the study was to determine whether risk of recurrent preterm birth differs based on the clinical presentation of a prior spontaneous preterm birth (SPTB): advanced cervical dilatation (ACD), preterm premature rupture of membranes (PPROM), or preterm labor (PTL)., Study Design: This retrospective cohort study included singleton pregnancies from 2009 to 2014 complicated by a history of prior SPTB. Women were categorized based on the clinical presentation of their prior preterm delivery as having ACD, PPROM, or PTL. Risks for sonographic short cervical length and recurrent SPTB were compared between women based on the clinical presentation of their prior preterm birth. Log-linear regression was used to control for confounders., Results: Of 522 patients included in this study, 96 (18.4%) had prior ACD, 246 (47.1%) had prior PPROM, and 180 (34.5%) had prior PTL. Recurrent PTB occurred in 55.2% of patients with a history of ACD compared with 27.2% of those with PPROM and 32.2% with PTL (P = .001). The mean gestational age at delivery was significantly lower for those with a history of ACD (34.0 weeks) compared with women with prior PPROM (37.2 weeks) or PTL (37.0 weeks) (P = .001). The lowest mean cervical length prior to 24 weeks was significantly shorter in patients with a history of advanced cervical dilation when compared with the other clinical presentations., Conclusion: Patients with a history of ACD are at an increased risk of having recurrent preterm birth and cervical shortening in a subsequent pregnancy compared with women with prior preterm birth associated PPROM or PTL., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics.

Intracellular bacterial pathogens engage in a tug-of-war with innate host defenses. In this issue of Cell Host & Microbe, Mostowy et al. (2010) identify a role for the septin family of cytoskeletal proteins in targeting intracellular Shigella to the autophagy pathway., (Copyright © 2010 Elsevier Inc. All rights reserved.)